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Inheritance

1

Autosomal dominant HP:0000006

OPN1SW lies on chromosome 7, so the defect affects males and females equally and is transmitted as an autosomal dominant trait. Penetrance is incomplete and expressivity variable: heterozygous relatives with the same variant differ in severity, from passing standard tests to tritanopia, and severity tends to increase with age. Rare homozygotes have been reported within two pedigrees.

Autosomal dominant inheritance Penetrance: INCOMPLETE Expressivity: VARIABLE

Show evidence (6 references)

PMID:1531728 SUPPORT BACKGROUND Human Clinical

"Tritanopia is an autosomal dominant genetic disorder of human vision characterize by a selective deficiency of blue spectral sensitivity."

States the autosomal dominant inheritance of tritanopia in the founding genotype study.

PMID:3872255 SUPPORT PRIMARY RESULT Human Clinical

"Tritan (blue-green) colour vision disturbances have been found in 79 individuals in six families, revealing an autosomal dominant mode of inheritance with a wide variability of test results within families."

Six-family pedigree study establishing autosomal dominant transmission and variable expressivity within families.

PMID:23022137 SUPPORT BACKGROUND Human Clinical

"The deficiency affects males and females equally and shows an autosomal dominant inheritance pattern."

Equal sex distribution and dominant transmission, as expected for an autosomal gene.

+ 3 more references

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Mechanistic Hypotheses

2

Dominant-negative mutant S-opsin causing progressive S-cone degeneration

dominant_negative_s_cone_degeneration EMERGING

Evidence balance 2 support

Each S cone expresses both autosomal OPN1SW alleles. Missense substitutions in the transmembrane helices are predicted to disturb folding, processing or stability of the opsin, and by analogy with dominant rhodopsin mutations in retinitis pigmentosa the mutant opsin is proposed to interfere with the normal one and reduce S-cone viability. S cones are then lost over years, so severity depends on disease stage, and heterozygotes need not be dichromatic until enough S cones have died. Supported by adaptive optics imaging of one R283Q family and by error scores that rise with age in several families.

Pathograph links

Heterozygous Germline OPN1SW Variant -> Misfolded Mutant S-Opsin DIRECT Missense substitutions in the transmembrane helices are predicted to disturb opsin folding, processing or stability.

Misfolded Mutant S-Opsin -> Progressive S-Cone Degeneration DIRECT Dominant-negative interaction between mutant and normal opsin is proposed to reduce S-cone viability.

Progressive S-Cone Degeneration -> Reduced S-Cone Signal DIRECT Loss of S cones removes the S-cone contribution to vision.

Progressive S-Cone Degeneration -> Cone Mosaic Irregularity After S-Cone Loss DIRECT L and M cones partly fill the gaps left by dead S cones.

Show evidence (2 references)

PMID:17429491 SUPPORT PRIMARY RESULT Human Clinical

"S-opsin mutations that cause autosomal dominant tritan color-vision deficiencies are analogous to rhodopsin mutations that cause autosomal dominant retinitis pigmentosa in which dominant negative interactions between normal and mutant pigments expressed in the same photoreceptor lead to the..."

States the dominant-negative degeneration model proposed from the imaging results.

PMID:17429491 SUPPORT PRIMARY RESULT Human Clinical

"Most individuals with inherited tritan deficiencies are heterozygous and, according to the hypothesis supported by the experimental data presented here, they need not exhibit complete dichromacy until the disorder has progressed to a stage when a critical number of S cones have lost viability."

Links the variable, age-dependent phenotype to progressive S-cone loss.

OPN1SW haploinsufficiency reducing S-cone photopigment

opn1sw_haploinsufficiency EMERGING

Evidence balance 1 support

For the intron 3 splice-donor deletion, the mutant allele produces a transcript skipping exons 2 and 3 that cannot encode functional opsin, so heterozygous S cones are expected to contain about half the normal opsin. Because S cones already receive few photons after lens and macular pigment absorption, halving photopigment is proposed to reduce S-cone signals enough to give a mild tritan defect. Supported by an in vitro splicing assay and one three-person family.

Pathograph links

Heterozygous Germline OPN1SW Variant -> Reduced S-Opsin Dosage DIRECT The intron 3 splice-donor deletion produces a transcript lacking exons 2 and 3 that cannot encode functional opsin.

Reduced S-Opsin Dosage -> Reduced S-Cone Signal DIRECT Halving photopigment in cones that already catch few photons is proposed to reduce their signal.

Show evidence (1 reference)

PMID:32400513 SUPPORT PRIMARY RESULT In Vitro

"Due to the splicing defect in the exon 3 +5G deletion OPN1SW allele, affected subjects are expected to have S cones with half the normal amount of S opsin, and the mechanism of tritan color vision deficiency caused by this mutation must be haploinsufficiency."

Haploinsufficiency inferred from the splicing assay result.

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Pathophysiology

7

Heterozygous Germline OPN1SW Variant

The initiating lesion is a heterozygous germline variant in OPN1SW (chromosome 7), the gene for the S-cone opsin. Reported alleles are missense substitutions (L56P, G79R, T190I, S214P, P264S, R283Q), all except T190I in transmembrane helices, and an intron 3 splice-donor deletion. The alleles were found in tritan probands or families; where controls were screened, the variants were absent from them.

Dominant-negative mutant S-opsin causing progressive S-cone degeneration OPN1SW haploinsufficiency reducing S-cone photopigment

OPN1SW hgnc:1012

Genetic context allele_type: missense or splice-site variant_origin: GERMLINE zygosity: HETEROZYGOUS

Downstream

Misfolded Mutant S-Opsin Missense substitutions in the transmembrane helices are predicted to disturb opsin folding, processing or stability.

Reduced S-Opsin Dosage The intron 3 splice-donor deletion produces a transcript lacking exons 2 and 3 that cannot encode functional opsin.

Show evidence (4 references)

PMID:1531728 SUPPORT PRIMARY RESULT Human Clinical

"Segregation analysis within pedigrees and hybridization of oligonucleotides specific for each allele to DNA samples from control subjects support the hypothesis that these mutations cause tritanopia."

Segregation and control screening support OPN1SW missense variants as the cause of tritanopia.

PMID:16961973 SUPPORT PRIMARY RESULT Human Clinical

"This mutation was absent in 564 S cone photopigment genes from 282 subjects who did not make tritan errors."

The L56P allele is absent from a large control series.

PMID:23022137 SUPPORT BACKGROUND Human Clinical

"Five mutations in the S-cone-opsin gene (OPN1SW) that give rise to different single amino-acid substitutions (L56P, G79R, S214P, P264S, R283Q) are known to be associated with tritan color-vision deficiency."

Lists the missense alleles reported before T190I.

+ 1 more reference

Misfolded Mutant S-Opsin

Mutant S-opsin is predicted to misfold or be unstable. Because each S cone expresses both OPN1SW alleles, whereas each L or M cone expresses a single X-linked opsin gene, mutant and normal S-opsin are made in the same cell, which allows a dominant-negative interaction of the kind seen with dominant rhodopsin mutations. No folding or trafficking assay of a tritan allele has been reported in the sources cited here.

Dominant-negative mutant S-opsin causing progressive S-cone degeneration

OPN1SW hgnc:1012

S-opsin folding GO:0006457 ⚠ ABNORMAL

short-wavelength G protein-coupled photoreceptor activity GO:0008020 ⚠ ABNORMAL

Downstream

Progressive S-Cone Degeneration Dominant-negative interaction between mutant and normal opsin is proposed to reduce S-cone viability.

Show evidence (1 reference)

PMID:17429491 SUPPORT BACKGROUND Human Clinical

"This is because each S cone expresses both autosomal copies of the S-opsin gene, whereas L and M cones each express only one opsin gene from the X chromosome."

Explains why S cones, unlike L and M cones, can host a dominant-negative interaction between mutant and normal opsin.

Reduced S-Opsin Dosage

For the intron 3 splice-donor allele, heterozygous S cones are expected to contain about half the normal S-opsin. The normal OPN1SW gene itself appears to splice inefficiently in the same assay, so S cones may already operate with less photopigment than L and M cones.

OPN1SW haploinsufficiency reducing S-cone photopigment

OPN1SW hgnc:1012

OPN1SW pre-mRNA splicing GO:0000398 ⚠ ABNORMAL

Downstream

Reduced S-Cone Signal Halving photopigment in cones that already catch few photons is proposed to reduce their signal.

Show evidence (2 references)

PMID:32400513 SUPPORT PRIMARY RESULT In Vitro

"Due to the splicing defect in the exon 3 +5G deletion OPN1SW allele, affected subjects are expected to have S cones with half the normal amount of S opsin, and the mechanism of tritan color vision deficiency caused by this mutation must be haploinsufficiency."

Halved S-opsin dosage inferred from the splicing assay.

PMID:32400513 SUPPORT PRIMARY RESULT In Vitro

"Inefficient splicing appears to be a feature of the OPN1SW gene."

The normal OPN1SW gene splices inefficiently in HEK293 cells, unlike the rhodopsin control.

Progressive S-Cone Degeneration

S cones are lost over time in heterozygotes. In an R283Q family, adaptive optics retinal densitometry found no S cones in the 57-year-old tritanopic father and a normal S-cone density in his mildly affected 34-year-old daughter. Colour vision error scores increase with age in several families, and the affected father recalled no colour problems when younger.

Dominant-negative mutant S-opsin causing progressive S-cone degeneration

S cone cell CL:0003050

S-cone photoreceptor maintenance GO:0045494 ↓ DECREASED

retina UBERON:0000966

Animal models

Opn1sw Neo/Neo S-opsin-null mouse Mouse (Mus musculus) fails to recapitulate Cones lacking S-opsin remain viable for at least 1.5 years, so loss of S-opsin alone does not reproduce S-cone death.

Downstream

Reduced S-Cone Signal Loss of S cones removes the S-cone contribution to vision.

Cone Mosaic Irregularity After S-Cone Loss L and M cones partly fill the gaps left by dead S cones.

Show evidence (4 references)

PMID:17429491 SUPPORT PRIMARY RESULT Human Clinical

"Adaptive optics was used to obtain high-resolution retinal images, which revealed distinctly different S-cone mosaics consistent with their discrepant phenotypes."

Two relatives with the same R283Q variant had different S-cone mosaics matching their different severities.

PMID:17429491 SUPPORT PRIMARY RESULT Human Clinical

"the absence of S cones coupled with the decreased density and abnormal packing arrangement of the cones in a tritan subject (M04) suggests that heterozygosity for the R283Q mutation ultimately results in the death of S cones."

Absence of S cones in the older carrier is interpreted as S-cone death.

PMID:17429491 SUPPORT PRIMARY RESULT Human Clinical

"These results taken together with other recent findings from molecular genetics indicate that, with rare exceptions, tritan deficiency is progressive in nature."

Concludes that the disorder is generally progressive.

+ 1 more reference

Cone Mosaic Irregularity After S-Cone Loss

In the tritanopic R283Q carrier lacking S cones, the overall cone mosaic was less regular than in controls (fewer six-sided Voronoi cells and a shorter nearest-neighbour distance than expected for his cone density). This is the only structural retinal change described; his ophthalmic examination was normal.

retina UBERON:0000966

Show evidence (2 references)

PMID:17429491 SUPPORT PRIMARY RESULT Human Clinical

"In addition, a significant disruption in the regularity of the overall cone mosaic was observed in the subject completely lacking S-cone function."

Cone mosaic irregularity in the carrier lacking S-cone function.

PMID:17429491 SUPPORT PRIMARY RESULT Human Clinical

"Ophthalmic examinations were normal on both father and daughter"

No other ophthalmic abnormality in the carriers.

Reduced S-Cone Signal

The S-cone contribution to vision is reduced or absent, measured psychophysically and as a reduced or unrecordable S-cone (blue cone) electroretinogram. S cones are normally only about 7% of cones near the fovea, so the system has little reserve. Some affected individuals keep S-cone function in large fields or at high light levels and lose it in small fields or at low retinal illuminance.

S cone cell CL:0003050

detection of short-wavelength light in visual perception GO:0050908 ↓ DECREASED

Downstream

Loss of S-Cone Opponent (Blue-Yellow) Signal Without an adequate S-cone input, the S-versus-(L+M) comparison underlying blue-yellow discrimination fails.

Reduced or Absent S-Cone Electroretinogram The S-cone ERG directly records the reduced S-cone response.

Show evidence (4 references)

PMID:305912 SUPPORT PRIMARY RESULT Human Clinical

"With the electroretinogram the sensitivity was also significantly lower than in normal subjects, thus indicating a retinal origin of the tritan defect."

Reduced blue cone ERG sensitivity places the defect in the retina.

PMID:1722224 SUPPORT INDIRECT PRIMARY RESULT Human Clinical

"7% of cones within 4 mm of the foveal center are labeled by antiblue opsin"

S cones are a small minority of cones in the normal human retina.

PMID:6977627 SUPPORT PRIMARY RESULT Human Clinical

"indicating that autosomal dominant tritans have short-wavelength-sensitive cones"

Many tritans retain some S-cone function in a large test field.

+ 1 more reference

Loss of S-Cone Opponent (Blue-Yellow) Signal

Blue-yellow (tritan) colour discrimination depends on comparing S-cone signals with combined L- and M-cone signals. When the S-cone signal is weak, colours along the tritan confusion axis are confused; when it is absent, vision along that axis is dichromatic. Red-green discrimination is unaffected. Left unbound to GO: the nearest process term, GO:0007601 visual perception, is broader than S-cone opponent comparison.

Downstream

Tritan Color Vision Defect A weakened S-cone opponent signal produces tritan colour confusions.

Tritanopia An absent S-cone signal leaves dichromatic vision along the tritan axis.

Abnormal Hardy-Rand-Rittler Tritan Plates The tritan screening plates detect failures of S-cone opponent discrimination.

Show evidence (1 reference)

PMID:23022137 SUPPORT PRIMARY RESULT Human Clinical

"The performance of subjects with the T190I mutation was significantly different from that of normal trichromats along the tritan vector under all conditions tested (Mann-Whitney U: p<0.05), but not along the protan or deutan vectors."

The discrimination deficit is confined to the tritan axis.

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Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.

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Phenotypes

4

Tritan Color Vision Defect Ophthalmologic HP:0000552

Course: PROGRESSIVE

HP:0000552 Tritanomaly is bound for the tritan defect as a whole because HPO lists blue-yellow color blindness and blue-yellow dyschromatopsia as its exact synonyms; HPO places it under anomalous trichromacy, and the dichromatic form is recorded separately below.

Show evidence (6 references)

PMID:16961973 SUPPORT PRIMARY RESULT Human Clinical

"made errors on standard color vision tests consistent with the presence of a mild tritan color vision deficiency"

Mild tritan defect in an L56P heterozygote.

PMID:23022137 SUPPORT PRIMARY RESULT Human Clinical

"FM100-Hue error scores increase with increasing age"

Within the T190I family, severity rises with age.

PMID:17429491 SUPPORT PRIMARY RESULT Human Clinical

"He reported that he could not remember having any problems with color vision when he was younger, and it was only in recent years that he has experienced difficulties with discriminating between some colors such as orange-yellow and pink."

Late-recognised, progressive colour confusion reported by a tritanopic carrier.

+ 3 more references

Tritanopia Ophthalmologic HP:0011518

Show evidence (3 references)

PMID:17429491 SUPPORT PRIMARY RESULT Human Clinical

"The father's behavior on all color-vision tests was that of a tritanope."

R283Q carrier with tritan dichromacy.

PMID:32400513 SUPPORT BACKGROUND Human Clinical

"Members of family C who had the P264S and a normal allele had tritanopia"

P264S heterozygotes had tritanopia.

PMID:6977627 SUPPORT PRIMARY RESULT Human Clinical

"Eleven tritans were dichromats with 1 degrees field, and only two were dichromats with an 8 degrees field."

Dichromacy is field-size dependent in autosomal dominant tritans.

Abnormal Hardy-Rand-Rittler Tritan Plates Ophthalmologic HP:0030587

Show evidence (2 references)

PMID:23022137 SUPPORT PRIMARY RESULT Human Clinical

"Members of the family with the T190I mutation all fail the tritan plates on HRR pseudo-isochromatic plates, and members of the family who lack the mutation pass the tritan plates"

HRR tritan plate failure segregates with the T190I variant.

PMID:17429491 SUPPORT PRIMARY RESULT Human Clinical

"He made tritan errors on the HRR pseudoisochromatic plates, the Lanthony's desaturated D15, and the Farnsworth D15"

The R283Q tritanope failed the HRR tritan plates.

Reduced or Absent S-Cone Electroretinogram Ophthalmologic HP:0008275

Show evidence (3 references)

PMID:3876823 SUPPORT PRIMARY RESULT Human Clinical

"The blue cone ERG confirmed a difference between the two groups; it was unrecordable in the patients with congenital tritanopia but within the normal range in those with DIJOA."

Blue cone ERG unrecordable in congenital tritanopia.

PMID:3485517 SUPPORT PRIMARY RESULT Human Clinical

"Compared with the response of normal subjects, a marked reduction or a lack of the blue cone responses was clearly shown in the spectral response patterns of tritanopes."

Spectral ERG shows reduced or absent blue cone responses.

PMID:3485517 SUPPORT PRIMARY RESULT Human Clinical

"Electroretinograms elicited by strong white stimulation or xenon flashes showed negative responses (a-waves larger than b-waves) with normal rod function in each tritanopic subject."

A single pedigree also had negative bright-flash ERGs, which the authors read as L- and M-cone involvement.

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Genetic Associations

1

OPN1SW (Genetic Mutation)

Gene: OPN1SW hgnc:1012 relationship_type: CAUSATIVE

Autosomal dominant

Show evidence (2 references)

PMID:1531728 SUPPORT PRIMARY RESULT Human Clinical

"to detect in four of nine unrelated tritanopic subjects two different point mutations in the gene encoding the blue-sensitive opsin, each leading to an amino acid substitution"

OPN1SW missense variants found in tritanopic probands.

PMID:23022137 SUPPORT PRIMARY RESULT Human Clinical

"All mutations in the OPN1SW gene that result in an amino acid substitution that have been observed to date are disease causing"

Authors' summary that all reported OPN1SW substitutions cause tritan defects.

Variants (7)

p.Leu56Pro (L56P)

missense

Found heterozygous in a 30-year-old man with a mild tritan defect; absent from 564 control OPN1SW genes.

Show evidence (1 reference)

PMID:16961973 SUPPORT PRIMARY RESULT Human Clinical

"He was found to be heterozygous for a mutation that caused the amino acid proline to be substituted in place of a highly conserved leucine at amino acid position 56 in the S cone opsin."

Identifies L56P in a tritan proband.

p.Gly79Arg (G79R)

missense

One of the two substitutions found in the founding genotype study of tritanopia. Also found in a sister and father in a Japanese family segregating homozygous PDE6C achromatopsia, where the authors suggested it might explain the sister's complete rather than incomplete achromatopsia.

Show evidence (2 references)

PMID:25605338 SUPPORT PRIMARY RESULT Human Clinical

"We also identified an OPN1SW mutation (p.G79R), which is associated with congenital tritan deficiencies, in the sister and the father but not in the brother."

G79R observed in a second, unrelated family; the possible modifier effect on achromatopsia severity is the authors' suggestion only.

PMID:23022137 SUPPORT BACKGROUND Human Clinical

"Five mutations in the S-cone-opsin gene (OPN1SW) that give rise to different single amino-acid substitutions (L56P, G79R, S214P, P264S, R283Q) are known to be associated with tritan color-vision deficiency."

Lists G79R among the tritan-associated OPN1SW substitutions.

p.Thr190Ile (T190I)

missense

Segregates with tritan errors in one family (nine heterozygous relatives); the only reported variant in extracellular loop II rather than a transmembrane helix.

Show evidence (1 reference)

PMID:23022137 SUPPORT PRIMARY RESULT Human Clinical

"Affected family members were heterozygous for a nucleotide change that substituted the amino acid isoleucine (I) in place of threonine (T) that is normally present at position 190 of the S-opsin."

Identifies T190I in affected relatives.

p.Ser214Pro (S214P)

missense

The second substitution found in the founding genotype study of tritanopia.

Show evidence (1 reference)

PMID:23022137 SUPPORT BACKGROUND Human Clinical

"Five mutations in the S-cone-opsin gene (OPN1SW) that give rise to different single amino-acid substitutions (L56P, G79R, S214P, P264S, R283Q) are known to be associated with tritan color-vision deficiency."

Lists S214P among the tritan-associated OPN1SW substitutions.

p.Pro264Ser (P264S)

missense

Associated with tritanopia in heterozygotes; reported separately as a third tritan substitution.

Show evidence (1 reference)

PMID:32400513 SUPPORT BACKGROUND Human Clinical

"Members of family C who had the P264S and a normal allele had tritanopia"

P264S heterozygotes had tritanopia.

p.Arg283Gln (R283Q)

missense

Heterozygous in a father with tritanopia and in his two children, who had a mild defect or none detected on standard tests; adaptive optics showed absent S cones in the father.

Show evidence (1 reference)

PMID:17429491 SUPPORT PRIMARY RESULT Human Clinical

"All 29 control subjects were homozygous for arginine."

R283Q was absent from the 29 controls sequenced alongside the family.

OPN1SW intron 3 +5G deletion (exon 3 splice donor)

splice donor variant

Deletion of the G five nucleotides into intron 3, disrupting the exon 3 splice donor; in vitro it yields only a transcript lacking exons 2 and 3, with a frameshift and premature stop. Heterozygotes in one family had a mild tritan defect.

Show evidence (1 reference)

PMID:32400513 SUPPORT PRIMARY RESULT In Vitro

"Direct sequencing of this product revealed that it represents a single isoform that lacks exons 2 and 3, and contains exon 1, 4 and 5 spliced together"

Splicing assay shows the allele yields only an exon 2-3 skipped transcript.

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Diagnosis

3

Tritan-sensitive colour vision testing

Tests with a tritan axis (Hardy-Rand-Rittler tritan plates, Farnsworth-Munsell 100-Hue, Lanthony desaturated D15, Cambridge Colour Test, Moreland anomaloscope) detect the defect. Ishihara plates test only red-green discrimination and are passed. Mild defects in young carriers can be missed under standard photopic conditions and become evident at low luminance.

colour vision testing NCIT:C156778

Show evidence (2 references)

PMID:17429491 SUPPORT PRIMARY RESULT Human Clinical

"He made no errors on the Ishihara pseudoisochromatic plates, nor on the Medmont C100"

A tritanope passed the Ishihara plates, which do not test the tritan axis.

PMID:23022137 SUPPORT PRIMARY RESULT Human Clinical

"the tritan color-vision deficiency associated with the T190I mutation may indeed go unnoticed if younger subjects only are tested with the FM100-Hue test"

Standard photopic testing can miss mild defects in young carriers.

S-cone electroretinography

The blue cone ERG is reduced or unrecordable in tritanopes and separates congenital tritan defects from dominant optic atrophy.

S-cone electroretinography NCIT:C101217

Show evidence (1 reference)

PMID:3876823 SUPPORT PRIMARY RESULT Human Clinical

"We believe that congenital tritanopia and DIJOA are distinct disease entities and that the blue cone ERG is a key factor in the differential diagnosis."

Recommends the blue cone ERG for differential diagnosis.

OPN1SW sequencing

Sequencing the coding exons and flanking intron sequence of OPN1SW identifies the causal variant and allows testing of relatives, who may be mildly affected or unaware of a defect.

Genetic Testing NCIT:C15709

Show evidence (1 reference)

PMID:16961973 SUPPORT PRIMARY RESULT Human Clinical

"We tested the hypothesis that his color vision impairment was due to a mutation in the S cone photopigment gene."

OPN1SW sequencing was used to identify the cause of a tritan defect.

📊

Prevalence

2

Screening series totalling 1900 individuals (Went and Pronk family and screening study)

Point Prevalence 200.0 per 100,000 >1 in 1,000

Estimated frequency of tritan disturbances around 2 per 1000 from three small screening series totalling 1900 individuals; a screening-test classification, not genotype-confirmed.

Show evidence (1 reference)

PMID:3872255 SUPPORT PRIMARY RESULT Human Clinical

"On the basis of three small screening series, totalling 1900 individuals, the frequency of tritan disturbances is estimated to be around 2 per 1000."

Screening-based estimate of tritan defect frequency.

Children and adolescents worldwide, males (pooled meta-analysis of 56 studies, 1932-2022)

Point Prevalence 670.0 per 100,000 (200.0–2220.0) >1 in 1,000

Pooled tritan prevalence in males 0.67% (95% CI 0.20-2.22%), from screening studies that classified defect type. The interval is wide, and screening tests cannot separate inherited OPN1SW defects from acquired tritan errors, so the figure is best read as an upper bound for the inherited disorder.

Show evidence (1 reference)

PMID:40769301 SUPPORT PRIMARY RESULT Human Clinical

"and tritan (male, 0.67% [95% CI, 0.20%-2.22%])"

Meta-analysis estimate of tritan prevalence in males.

🔀

Differential Diagnoses

3

Conditions with similar clinical presentations that must be differentiated from Tritan Color Vision Deficiency:

Autosomal dominant optic atrophy MONDO:0008134

Overlapping Features Dominantly inherited juvenile optic atrophy also produces tritan errors and was once thought to be the same entity as congenital tritanopia.

Distinguishing Features

Blue cone ERG within the normal range.
Optic atrophy, which can be ruled out in tritan pedigrees.

Show evidence (2 references)

PMID:3876823 SUPPORT PRIMARY RESULT Human Clinical

"The blue cone ERG confirmed a difference between the two groups; it was unrecordable in the patients with congenital tritanopia but within the normal range in those with DIJOA."

The blue cone ERG distinguishes the two conditions.

PMID:6606981 SUPPORT PRIMARY RESULT Human Clinical

"This report describes the results of testing 34 members of a pedigree (including four tritans) for whom optic atrophy can be ruled out"

A tritan pedigree without optic atrophy shows the two are separable.

Blue cone monochromacy MONDO:0010563

Overlapping Features X-linked loss of L- and M-cone function in which S cones remain; the reverse of the tritan defect despite the similar name.

Distinguishing Features

X-linked inheritance.
L- and M-cone function absent while S-cone function is retained.

Show evidence (1 reference)

PMID:15312026 SUPPORT REVIEW SYNTHESIS Other

"Blue cone monochromacy is a rare form of colour vision deficiency that results from mutations that abolish function of both the L and M pigment genes."

Defines blue cone monochromacy as loss of L and M pigment function.

Autosomal dominant cone dystrophy with early tritanopia (16q12 IRXB duplication) MONDO:0000455

Overlapping Features Tandem duplications of the IRXB gene cluster (IRX5, IRX6) on chromosome 16q12 cause an autosomal dominant progressive cone dystrophy whose earliest sign is a tritan colour vision defect, so the inheritance pattern and the first colour vision finding mimic the OPN1SW disorder. No specific MONDO term was found, so the general cone dystrophy term is bound.

Distinguishing Features

Progressive cone dystrophy with declining visual acuity and central vision loss.
Copy-number gain at 16q12 rather than an OPN1SW sequence variant.

Show evidence (1 reference)

PMID:33891002 SUPPORT PRIMARY RESULT Human Clinical

"All patients presented with a unique progressive cone dystrophy phenotype hallmarked by early tritanopic color vision defects."

A dominant cone dystrophy that begins with tritan defects is a genetic phenocopy of the early OPN1SW phenotype.

🐁

Animal Models

1

Opn1sw Neo/Neo S-opsin-null mouse

Mouse lacking S-opsin expression. It is not a model of a human tritan allele: it carries no missense or splice variant and is homozygous null, and most mouse cones co-express M and S opsin. It is recorded because its cones survive without S-opsin, which bears on the mechanism of S-cone loss.

Species

Mouse (Mus musculus)

Genotype

Opn1sw(Neo/Neo), neomycin cassette inserted between exons 3 and 4 of Opn1sw

Publication

PMID:21219924

Pathograph links

Progressive S-Cone Degeneration fails to recapitulate fidelity: low observes: cellular Cones lacking S-opsin remain viable for at least 1.5 years, so loss of S-opsin alone does not reproduce S-cone death.

Limitations: A null allele cannot test the proposed dominant-negative toxicity of a mutant human S-opsin, and mouse cones that co-express M opsin are not equivalent to human S cones, which express S opsin alone.

Divergences from the human mechanism

cause unrepresented qualifying

The human lesion is a heterozygous missense or splice allele; the mouse has no S-opsin at all, so a toxic mutant protein, the proposed cause of S-cone death, is absent.

species mismatch qualifying

Most mouse cones co-express M and S opsin in dorso-ventral gradients, whereas the human S cone expresses only S opsin, so a mouse cone losing S-opsin keeps a photopigment and the human S cone would not.

Show evidence (2 references)

PMID:21219924 SUPPORT PRIMARY RESULT Model Organism

"cones of the Opn1sw(Neo/Neo) mouse remain viable for at least 1.5 yrs, even though many ventral cones do not form outer segments"

S-opsin-null cones survive long term.

+ 1 more reference

{ }

Source YAML

click to show

name: Tritan Color Vision Deficiency
creation_date: "2026-10-14T20:49:40Z"
category: Mendelian
parents:
- Color vision disorder
- Inherited retinal disease
description: >-
  Autosomal dominant blue-yellow (tritan) colour vision deficiency caused by
  heterozygous variants in OPN1SW, the chromosome 7 gene encoding the
  short-wavelength-sensitive (S, "blue") cone opsin. Unlike the X-linked
  red-green defects, it affects males and females equally. Six missense
  substitutions (L56P, G79R, T190I, S214P, P264S, R283Q) and an intron 3 splice
  donor deletion have been reported in affected families. Penetrance is
  incomplete and expressivity is variable: relatives sharing a variant range from
  apparently normal colour vision to tritanopia, and error scores rise with age.
  Adaptive optics imaging of an R283Q family showed absence of S cones in the
  older, tritanopic carrier but a normal S-cone mosaic in his mildly affected
  daughter, so in heterozygotes the defect is thought to be a slowly progressive
  S-cone dystrophy, attributed to dominant-negative effects of the mutant opsin,
  rather than a stationary congenital trait. A splice allele that halves S-opsin
  dosage gives a milder defect, consistent with haploinsufficiency. Visual
  acuity and the ophthalmic examination are normal, Ishihara plates do not detect
  the defect, and no disease-specific treatment has been reported.
disease_term:
  preferred_term: blue color blindness
  term:
    id: MONDO:0008610
    label: blue color blindness
synonyms:
- blue color blindness
- tritanopia
- tritanomaly
- tritan defect
- tritan color blindness
- tritan colour blindness
- congenital tritanopia
- autosomal dominant tritan defect
- inherited tritan color vision deficiency
notes: >-
  Scope and naming. The MONDO term (OMIM:190900, Orphanet:88629) is labelled blue
  color blindness and its definition and synonyms describe tritanopia, but this
  entry covers the whole inherited tritan series (tritanopia and milder tritan
  defects) caused by OPN1SW variants. Acquired tritan defects (for example from
  lens yellowing, glaucoma, diabetic retinopathy, drug toxicity or dominant optic
  atrophy) are out of scope; they are not OPN1SW disorders. Lump/split:
  tritanopia and tritanomaly are not split into subtypes, because a six-family
  study found a continuum of test results within families and judged a
  dichromatic versus anomalous-trichromatic subdivision incorrect for tritan
  defects, and because anomalous tritan colour matches have been attributed to
  rod intrusion rather than to a spectrally shifted S pigment (both cited on the
  phenotypes below). Relation to blue cone monochromacy: the names are easily
  confused but the disorders are opposites. Blue cone monochromacy (its own
  entry, Blue_Cone_Monochromacy, MONDO:0010563) is an X-linked loss of L- and
  M-cone function in which S cones remain, whereas the tritan defect is an
  autosomal dominant loss of S-cone function with normal L and M cones.
  Relation to the red-green defects: the protan and deutan defects
  (Protan_Color_Vision_Deficiency and the deutan stub) arise from the X-linked
  OPN1LW/OPN1MW array and are separate diseases. Mechanism status: OPN1SW
  causation rests on segregation in a small number of families plus absence of
  the variants in controls; the dominant-negative S-cone degeneration model
  rests on adaptive optics imaging of one R283Q family, and haploinsufficiency
  on an in vitro splicing assay of one allele, so both are recorded as emerging
  hypotheses. The T190I family's loss of S-cone sensitivity at low retinal
  illuminance was tentatively attributed by its authors to constitutive
  activation of cone transducin; that suggestion has no direct test and is not
  modelled as a node. Not cited, and why: the original P264S report
  (PMID:1386496) and the early pedigree papers PMID:13249225, PMID:14128207,
  PMID:4542649, PMID:4540298, PMID:4546850 and PMID:310059 returned no abstract
  or full text on the fetches made, so nothing in them could be quoted; P264S is
  cited through the later papers that describe it. No GeneReviews chapter exists
  for tritan colour vision deficiency (just check-genereviews against the
  Bookshelf index plus a live PubMed genereviews[book] title search). Animal
  models: a PubMed search for (OPN1SW OR "S-opsin" OR "blue opsin" OR
  "blue-sensitive opsin" OR "short-wavelength-sensitive opsin" OR "blue cone
  pigment") AND (mutation OR variant OR tritan OR misfold* OR dominant), run on
  2026-10-14, returned no animal carrying a human tritan OPN1SW allele; the
  S-opsin-null mouse is recorded under animal_models only for what it shows
  about S-cone survival. Course: some secondary sources describe the disorder as
  congenital and stationary, partly on the strength of S-opsin-null mouse cones
  surviving. The human adaptive optics and family age data cited here point to
  slow progression in heterozygotes, and a null allele does not test the
  dominant-negative model, so the entry records the course as progressive.
inheritance:
- name: Autosomal dominant
  inheritance_term:
    preferred_term: Autosomal dominant inheritance
    term:
      id: HP:0000006
      label: Autosomal dominant inheritance
  penetrance: INCOMPLETE
  expressivity: VARIABLE
  description: >-
    OPN1SW lies on chromosome 7, so the defect affects males and females equally
    and is transmitted as an autosomal dominant trait. Penetrance is incomplete and
    expressivity variable: heterozygous relatives with the same variant differ in
    severity, from passing standard tests to tritanopia, and severity tends to
    increase with age. Rare homozygotes have been reported within two pedigrees.
  evidence:
  - reference: PMID:1531728
    reference_title: "Human tritanopia associated with two amino acid substitutions in the blue-sensitive opsin."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Tritanopia is an autosomal dominant genetic disorder of human vision
      characterize by a selective deficiency of blue spectral sensitivity.
    explanation: >-
      States the autosomal dominant inheritance of tritanopia in the founding
      genotype study.
    quote_role: BACKGROUND
  - reference: PMID:3872255
    reference_title: "The genetics of tritan disturbances."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Tritan (blue-green) colour vision disturbances have been found in 79
      individuals in six families, revealing an autosomal dominant mode of
      inheritance with a wide variability of test results within families.
    explanation: >-
      Six-family pedigree study establishing autosomal dominant transmission and
      variable expressivity within families.
    quote_role: PRIMARY_RESULT
  - reference: PMID:23022137
    reference_title: "Substitution of isoleucine for threonine at position 190 of S-opsin causes S-cone-function abnormalities."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The deficiency affects males and females equally and shows an autosomal
      dominant inheritance pattern.
    explanation: >-
      Equal sex distribution and dominant transmission, as expected for an
      autosomal gene.
    quote_role: BACKGROUND
  - reference: PMID:17429491
    reference_title: "Adaptive optics retinal imaging reveals S-cone dystrophy in tritan color-vision deficiency."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The disorder exhibits incomplete penetrance, meaning that individuals with
      the same underlying mutation manifest different degrees of color-vision
      impairment, even within a sibship.
    explanation: >-
      Incomplete penetrance and variable expressivity among carriers of the same
      variant.
    quote_role: BACKGROUND
  - reference: PMID:42346125
    reference_title: "Cone Opsins and Inherited Retinal Disease."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Missense mutations in Opn1sw lead to tritanopia color vision deficiencies
      (Figure 3B) that are inherited in an autosomal dominant pattern with
      incomplete penetrance, affecting both males and females equally
    explanation: >-
      Recent review summarising dominant inheritance with incomplete penetrance.
    quote_role: REVIEW_SYNTHESIS
  - reference: PMID:17429491
    reference_title: "Adaptive optics retinal imaging reveals S-cone dystrophy in tritan color-vision deficiency."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      tritan individuals from two of the five pedigrees that have been studied in
      detail contain individuals who are homozygous for an S-opsin mutation, but
      there are also individuals within these two pedigrees who are heterozygous.
    explanation: >-
      Homozygotes occur but are rare; most affected individuals are heterozygous.
    quote_role: REVIEW_SYNTHESIS
prevalence:
- population: Screening series totalling 1900 individuals (Went and Pronk family and screening study)
  measure_type: POINT_PREVALENCE
  prevalence_class: ABOVE_1_IN_1000
  rate_per_100000: 200.0
  notes: >-
    Estimated frequency of tritan disturbances around 2 per 1000 from three small
    screening series totalling 1900 individuals; a screening-test classification,
    not genotype-confirmed.
  evidence:
  - reference: PMID:3872255
    reference_title: "The genetics of tritan disturbances."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      On the basis of three small screening series, totalling 1900 individuals,
      the frequency of tritan disturbances is estimated to be around 2 per 1000.
    explanation: >-
      Screening-based estimate of tritan defect frequency.
    quote_role: PRIMARY_RESULT
- population: Children and adolescents worldwide, males (pooled meta-analysis of 56 studies, 1932-2022)
  measure_type: POINT_PREVALENCE
  prevalence_class: ABOVE_1_IN_1000
  rate_per_100000: 670.0
  rate_low: 200.0
  rate_high: 2220.0
  notes: >-
    Pooled tritan prevalence in males 0.67% (95% CI 0.20-2.22%), from screening
    studies that classified defect type. The interval is wide, and screening
    tests cannot separate inherited OPN1SW defects from acquired tritan errors,
    so the figure is best read as an upper bound for the inherited disorder.
  evidence:
  - reference: PMID:40769301
    reference_title: "Global Prevalence of Congenital Color Vision Deficiency among Children and Adolescents, 1932-2022."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      and tritan (male, 0.67% [95% CI, 0.20%-2.22%])
    explanation: >-
      Meta-analysis estimate of tritan prevalence in males.
    quote_role: PRIMARY_RESULT
mechanistic_hypotheses:
- hypothesis_group_id: dominant_negative_s_cone_degeneration
  hypothesis_label: Dominant-negative mutant S-opsin causing progressive S-cone degeneration
  status: EMERGING
  description: >-
    Each S cone expresses both autosomal OPN1SW alleles. Missense substitutions in
    the transmembrane helices are predicted to disturb folding, processing or
    stability of the opsin, and by analogy with dominant rhodopsin mutations in
    retinitis pigmentosa the mutant opsin is proposed to interfere with the
    normal one and reduce S-cone viability. S cones are then lost over years, so
    severity depends on disease stage, and heterozygotes need not be dichromatic
    until enough S cones have died. Supported by adaptive optics imaging of one
    R283Q family and by error scores that rise with age in several families.
  evidence:
  - reference: PMID:17429491
    reference_title: "Adaptive optics retinal imaging reveals S-cone dystrophy in tritan color-vision deficiency."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      S-opsin mutations that cause autosomal dominant tritan color-vision
      deficiencies are analogous to rhodopsin mutations that cause autosomal
      dominant retinitis pigmentosa in which dominant negative interactions
      between normal and mutant pigments expressed in the same photoreceptor lead
      to the death of the affected photoreceptor.
    explanation: >-
      States the dominant-negative degeneration model proposed from the imaging
      results.
    quote_role: PRIMARY_RESULT
  - reference: PMID:17429491
    reference_title: "Adaptive optics retinal imaging reveals S-cone dystrophy in tritan color-vision deficiency."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Most individuals with inherited tritan deficiencies are heterozygous and,
      according to the hypothesis supported by the experimental data presented
      here, they need not exhibit complete dichromacy until the disorder has
      progressed to a stage when a critical number of S cones have lost viability.
    explanation: >-
      Links the variable, age-dependent phenotype to progressive S-cone loss.
    quote_role: PRIMARY_RESULT
- hypothesis_group_id: opn1sw_haploinsufficiency
  hypothesis_label: OPN1SW haploinsufficiency reducing S-cone photopigment
  status: EMERGING
  description: >-
    For the intron 3 splice-donor deletion, the mutant allele produces a
    transcript skipping exons 2 and 3 that cannot encode functional opsin, so
    heterozygous S cones are expected to contain about half the normal opsin.
    Because S cones already receive few photons after lens and macular pigment
    absorption, halving photopigment is proposed to reduce S-cone signals enough
    to give a mild tritan defect. Supported by an in vitro splicing assay and one
    three-person family.
  evidence:
  - reference: PMID:32400513
    reference_title: "Tritan color vision deficiency may be associated with an OPN1SW splicing defect and haploinsufficiency."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Due to the splicing defect in the exon 3 +5G deletion OPN1SW allele,
      affected subjects are expected to have S cones with half the normal amount
      of S opsin, and the mechanism of tritan color vision deficiency caused by
      this mutation must be haploinsufficiency.
    explanation: >-
      Haploinsufficiency inferred from the splicing assay result.
    quote_role: PRIMARY_RESULT
pathophysiology:
- name: Heterozygous Germline OPN1SW Variant
  description: >-
    The initiating lesion is a heterozygous germline variant in OPN1SW
    (chromosome 7), the gene for the S-cone opsin. Reported alleles are missense
    substitutions (L56P, G79R, T190I, S214P, P264S, R283Q), all except T190I in
    transmembrane helices, and an intron 3 splice-donor deletion. The alleles
    were found in tritan probands or families; where controls were screened, the
    variants were absent from them.
  biological_scale: MOLECULAR
  genes:
  - preferred_term: OPN1SW
    term:
      id: hgnc:1012
      label: OPN1SW
  genetic_context:
    variant_origin: GERMLINE
    zygosity: HETEROZYGOUS
    allele_type: missense or splice-site
  evidence:
  - reference: PMID:1531728
    reference_title: "Human tritanopia associated with two amino acid substitutions in the blue-sensitive opsin."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Segregation analysis within pedigrees and hybridization of oligonucleotides
      specific for each allele to DNA samples from control subjects support the
      hypothesis that these mutations cause tritanopia.
    explanation: >-
      Segregation and control screening support OPN1SW missense variants as the
      cause of tritanopia.
    quote_role: PRIMARY_RESULT
  - reference: PMID:16961973
    reference_title: "A novel mutation in the short-wavelength-sensitive cone pigment gene associated with a tritan color vision defect."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This mutation was absent in 564 S cone photopigment genes from 282 subjects
      who did not make tritan errors.
    explanation: >-
      The L56P allele is absent from a large control series.
    quote_role: PRIMARY_RESULT
  - reference: PMID:23022137
    reference_title: "Substitution of isoleucine for threonine at position 190 of S-opsin causes S-cone-function abnormalities."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Five mutations in the S-cone-opsin gene (OPN1SW) that give rise to different
      single amino-acid substitutions (L56P, G79R, S214P, P264S, R283Q) are known
      to be associated with tritan color-vision deficiency.
    explanation: >-
      Lists the missense alleles reported before T190I.
    quote_role: BACKGROUND
  - reference: PMID:15312026
    reference_title: "Molecular genetics of colour vision deficiencies."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Tritanopia is also a rare autosomal dominant colour vision defect caused by
      mutations in the S pigment gene located on chromosome 7.
    explanation: >-
      Review placing the causal gene on chromosome 7.
    quote_role: REVIEW_SYNTHESIS
  downstream:
  - target: Misfolded Mutant S-Opsin
    causal_link_type: DIRECT
    hypothesis_groups:
    - dominant_negative_s_cone_degeneration
    description: >-
      Missense substitutions in the transmembrane helices are predicted to disturb
      opsin folding, processing or stability.
    evidence:
    - reference: PMID:17429491
      reference_title: "Adaptive optics retinal imaging reveals S-cone dystrophy in tritan color-vision deficiency."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Each substitution occurs at an amino acid position that lies in one of the
        transmembrane alpha helices and is predicted to interfere with folding,
        processing, or stability of the encoded opsin.
      explanation: >-
        Structural prediction linking the missense alleles to opsin misfolding; no
        biochemical folding assay of a tritan allele is cited.
      quote_role: BACKGROUND
      directness: INDIRECT
  - target: Reduced S-Opsin Dosage
    causal_link_type: DIRECT
    hypothesis_groups:
    - opn1sw_haploinsufficiency
    description: >-
      The intron 3 splice-donor deletion produces a transcript lacking exons 2 and
      3 that cannot encode functional opsin.
    evidence:
    - reference: PMID:32400513
      reference_title: "Tritan color vision deficiency may be associated with an OPN1SW splicing defect and haploinsufficiency."
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: >-
        Direct sequencing of this product revealed that it represents a single
        isoform that lacks exons 2 and 3, and contains exon 1, 4 and 5 spliced
        together
      explanation: >-
        HEK293 splicing assay shows the mutant allele yields only an exon 2-3
        skipped transcript.
      quote_role: PRIMARY_RESULT
- name: Misfolded Mutant S-Opsin
  description: >-
    Mutant S-opsin is predicted to misfold or be unstable. Because each S cone
    expresses both OPN1SW alleles, whereas each L or M cone expresses a single
    X-linked opsin gene, mutant and normal S-opsin are made in the same cell,
    which allows a dominant-negative interaction of the kind seen with dominant
    rhodopsin mutations. No folding or trafficking assay of a tritan allele has
    been reported in the sources cited here.
  biological_scale: MOLECULAR
  genes:
  - preferred_term: OPN1SW
    term:
      id: hgnc:1012
      label: OPN1SW
  biological_processes:
  - preferred_term: S-opsin folding
    term:
      id: GO:0006457
      label: protein folding
    modifier: ABNORMAL
  molecular_functions:
  - preferred_term: short-wavelength G protein-coupled photoreceptor activity
    term:
      id: GO:0008020
      label: G protein-coupled photoreceptor activity
    modifier: ABNORMAL
  evidence:
  - reference: PMID:17429491
    reference_title: "Adaptive optics retinal imaging reveals S-cone dystrophy in tritan color-vision deficiency."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This is because each S cone expresses both autosomal copies of the S-opsin
      gene, whereas L and M cones each express only one opsin gene from the X
      chromosome.
    explanation: >-
      Explains why S cones, unlike L and M cones, can host a dominant-negative
      interaction between mutant and normal opsin.
    quote_role: BACKGROUND
  downstream:
  - target: Progressive S-Cone Degeneration
    causal_link_type: DIRECT
    hypothesis_groups:
    - dominant_negative_s_cone_degeneration
    description: >-
      Dominant-negative interaction between mutant and normal opsin is proposed to
      reduce S-cone viability.
    evidence:
    - reference: PMID:17429491
      reference_title: "Adaptive optics retinal imaging reveals S-cone dystrophy in tritan color-vision deficiency."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        S-opsin mutations that cause autosomal dominant tritan color-vision
        deficiencies are analogous to rhodopsin mutations that cause autosomal
        dominant retinitis pigmentosa in which dominant negative interactions
        between normal and mutant pigments expressed in the same photoreceptor lead
        to the death of the affected photoreceptor.
      explanation: >-
        Proposes that the mutant opsin kills S cones through dominant-negative
        interaction; the step is inferred by analogy with rhodopsin.
      quote_role: PRIMARY_RESULT
      directness: INDIRECT
- name: Reduced S-Opsin Dosage
  description: >-
    For the intron 3 splice-donor allele, heterozygous S cones are expected to
    contain about half the normal S-opsin. The normal OPN1SW gene itself appears
    to splice inefficiently in the same assay, so S cones may already operate with
    less photopigment than L and M cones.
  biological_scale: MOLECULAR
  genes:
  - preferred_term: OPN1SW
    term:
      id: hgnc:1012
      label: OPN1SW
  biological_processes:
  - preferred_term: OPN1SW pre-mRNA splicing
    term:
      id: GO:0000398
      label: mRNA splicing, via spliceosome
    modifier: ABNORMAL
  evidence:
  - reference: PMID:32400513
    reference_title: "Tritan color vision deficiency may be associated with an OPN1SW splicing defect and haploinsufficiency."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Due to the splicing defect in the exon 3 +5G deletion OPN1SW allele,
      affected subjects are expected to have S cones with half the normal amount
      of S opsin, and the mechanism of tritan color vision deficiency caused by
      this mutation must be haploinsufficiency.
    explanation: >-
      Halved S-opsin dosage inferred from the splicing assay.
    quote_role: PRIMARY_RESULT
  - reference: PMID:32400513
    reference_title: "Tritan color vision deficiency may be associated with an OPN1SW splicing defect and haploinsufficiency."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Inefficient splicing appears to be a feature of the OPN1SW gene.
    explanation: >-
      The normal OPN1SW gene splices inefficiently in HEK293 cells, unlike the
      rhodopsin control.
    quote_role: PRIMARY_RESULT
  downstream:
  - target: Reduced S-Cone Signal
    causal_link_type: DIRECT
    hypothesis_groups:
    - opn1sw_haploinsufficiency
    description: >-
      Halving photopigment in cones that already catch few photons is proposed to
      reduce their signal.
    evidence:
    - reference: PMID:32400513
      reference_title: "Tritan color vision deficiency may be associated with an OPN1SW splicing defect and haploinsufficiency."
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: >-
        Consider the scenario that S-cones normally operate near their lower
        limits, then halving the amount of photopigment available to absorb light,
        this would be expected to result in loss of S-cone signals and manifest as
        a tritan defect.
      explanation: >-
        The authors' proposed link from halved opsin to loss of S-cone signal; a
        reasoned argument rather than a measurement.
      quote_role: PRIMARY_RESULT
      directness: INDIRECT
- name: Progressive S-Cone Degeneration
  description: >-
    S cones are lost over time in heterozygotes. In an R283Q family, adaptive
    optics retinal densitometry found no S cones in the 57-year-old tritanopic
    father and a normal S-cone density in his mildly affected 34-year-old
    daughter. Colour vision error scores increase with age in several families,
    and the affected father recalled no colour problems when younger.
  biological_scale: CELLULAR
  cell_types:
  - preferred_term: S cone cell
    term:
      id: CL:0003050
      label: S cone cell
  biological_processes:
  - preferred_term: S-cone photoreceptor maintenance
    term:
      id: GO:0045494
      label: photoreceptor cell maintenance
    modifier: DECREASED
  locations:
  - preferred_term: retina
    term:
      id: UBERON:0000966
      label: retina
  evidence:
  - reference: PMID:17429491
    reference_title: "Adaptive optics retinal imaging reveals S-cone dystrophy in tritan color-vision deficiency."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Adaptive optics was used to obtain high-resolution retinal images, which
      revealed distinctly different S-cone mosaics consistent with their
      discrepant phenotypes.
    explanation: >-
      Two relatives with the same R283Q variant had different S-cone mosaics
      matching their different severities.
    quote_role: PRIMARY_RESULT
  - reference: PMID:17429491
    reference_title: "Adaptive optics retinal imaging reveals S-cone dystrophy in tritan color-vision deficiency."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      the absence of S cones coupled with the decreased density and abnormal
      packing arrangement of the cones in a tritan subject (M04) suggests that
      heterozygosity for the R283Q mutation ultimately results in the death of S
      cones.
    explanation: >-
      Absence of S cones in the older carrier is interpreted as S-cone death.
    quote_role: PRIMARY_RESULT
  - reference: PMID:17429491
    reference_title: "Adaptive optics retinal imaging reveals S-cone dystrophy in tritan color-vision deficiency."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      These results taken together with other recent findings from molecular
      genetics indicate that, with rare exceptions, tritan deficiency is
      progressive in nature.
    explanation: >-
      Concludes that the disorder is generally progressive.
    quote_role: PRIMARY_RESULT
  - reference: PMID:42346125
    reference_title: "Cone Opsins and Inherited Retinal Disease."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Patients with Opn1sw mutations present with progressive tritanopia; tritan
      defects may take several decades to progress from mild to moderate deficits
    explanation: >-
      Review summary of slow progression.
    quote_role: REVIEW_SYNTHESIS
  downstream:
  - target: Reduced S-Cone Signal
    causal_link_type: DIRECT
    hypothesis_groups:
    - dominant_negative_s_cone_degeneration
    description: >-
      Loss of S cones removes the S-cone contribution to vision.
    evidence:
    - reference: PMID:32400513
      reference_title: "Tritan color vision deficiency may be associated with an OPN1SW splicing defect and haploinsufficiency."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Adaptive optics imaging of related individuals affected by the R283Q
        mutation suggested a progressive S cone degeneration that is correlated
        with progressively deteriorating blue-yellow color vision
      explanation: >-
        Links S-cone degeneration to worsening blue-yellow colour vision.
      quote_role: BACKGROUND
  - target: Cone Mosaic Irregularity After S-Cone Loss
    causal_link_type: DIRECT
    hypothesis_groups:
    - dominant_negative_s_cone_degeneration
    description: >-
      L and M cones partly fill the gaps left by dead S cones.
    evidence:
    - reference: PMID:17429491
      reference_title: "Adaptive optics retinal imaging reveals S-cone dystrophy in tritan color-vision deficiency."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        The Voronoi and nearest-neighbor analyses suggest that some reorganization
        of the cone mosaic took place after the S cones had died
      explanation: >-
        Mosaic reorganisation follows S-cone death.
      quote_role: PRIMARY_RESULT
- name: Cone Mosaic Irregularity After S-Cone Loss
  description: >-
    In the tritanopic R283Q carrier lacking S cones, the overall cone mosaic was
    less regular than in controls (fewer six-sided Voronoi cells and a shorter
    nearest-neighbour distance than expected for his cone density). This is the
    only structural retinal change described; his ophthalmic examination was
    normal.
  biological_scale: TISSUE
  locations:
  - preferred_term: retina
    term:
      id: UBERON:0000966
      label: retina
  evidence:
  - reference: PMID:17429491
    reference_title: "Adaptive optics retinal imaging reveals S-cone dystrophy in tritan color-vision deficiency."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In addition, a significant disruption in the regularity of the overall cone
      mosaic was observed in the subject completely lacking S-cone function.
    explanation: >-
      Cone mosaic irregularity in the carrier lacking S-cone function.
    quote_role: PRIMARY_RESULT
  - reference: PMID:17429491
    reference_title: "Adaptive optics retinal imaging reveals S-cone dystrophy in tritan color-vision deficiency."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Ophthalmic examinations were normal on both father and daughter
    explanation: >-
      No other ophthalmic abnormality in the carriers.
    quote_role: PRIMARY_RESULT
- name: Reduced S-Cone Signal
  description: >-
    The S-cone contribution to vision is reduced or absent, measured
    psychophysically and as a reduced or unrecordable S-cone (blue cone)
    electroretinogram. S cones are normally only about 7% of cones near the fovea,
    so the system has little reserve. Some affected individuals keep S-cone
    function in large fields or at high light levels and lose it in small fields
    or at low retinal illuminance.
  biological_scale: CELLULAR
  cell_types:
  - preferred_term: S cone cell
    term:
      id: CL:0003050
      label: S cone cell
  biological_processes:
  - preferred_term: detection of short-wavelength light in visual perception
    term:
      id: GO:0050908
      label: detection of light stimulus involved in visual perception
    modifier: DECREASED
  evidence:
  - reference: PMID:305912
    reference_title: "Blue cone function in a family with an inherited tritan defect, tested with electroretinography and psychophysics."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      With the electroretinogram the sensitivity was also significantly lower than
      in normal subjects, thus indicating a retinal origin of the tritan defect.
    explanation: >-
      Reduced blue cone ERG sensitivity places the defect in the retina.
    quote_role: PRIMARY_RESULT
  - reference: PMID:1722224
    reference_title: "Distribution and morphology of human cone photoreceptors stained with anti-blue opsin."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      7% of cones within 4 mm of the foveal center are labeled by antiblue opsin
    explanation: >-
      S cones are a small minority of cones in the normal human retina.
    quote_role: PRIMARY_RESULT
    directness: INDIRECT
  - reference: PMID:6977627
    reference_title: "Color matching in autosomal dominant tritan defect."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      indicating that autosomal dominant tritans have short-wavelength-sensitive
      cones
    explanation: >-
      Many tritans retain some S-cone function in a large test field.
    quote_role: PRIMARY_RESULT
  - reference: PMID:23022137
    reference_title: "Substitution of isoleucine for threonine at position 190 of S-opsin causes S-cone-function abnormalities."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Individuals with the T190I S-opsin mutation behaved as mild tritans at
      12.3-92.3Td, but as tritanopes at 1.2-9.2Td, for both light-adapted and
      dark-adapted conditions.
    explanation: >-
      S-cone function in T190I carriers fails at low retinal illuminance.
    quote_role: PRIMARY_RESULT
  downstream:
  - target: Loss of S-Cone Opponent (Blue-Yellow) Signal
    causal_link_type: DIRECT
    description: >-
      Without an adequate S-cone input, the S-versus-(L+M) comparison underlying
      blue-yellow discrimination fails.
  - target: Reduced or Absent S-Cone Electroretinogram
    causal_link_type: DIRECT
    description: >-
      The S-cone ERG directly records the reduced S-cone response.
    evidence:
    - reference: PMID:3485517
      reference_title: "The electroretinographic characteristics of congenital tritan defects."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Compared with the response of normal subjects, a marked reduction or a
        lack of the blue cone responses was clearly shown in the spectral response
        patterns of tritanopes.
      explanation: >-
        Spectral ERG shows reduced or absent blue cone responses in tritanopes.
      quote_role: PRIMARY_RESULT
- name: Loss of S-Cone Opponent (Blue-Yellow) Signal
  description: >-
    Blue-yellow (tritan) colour discrimination depends on comparing S-cone signals
    with combined L- and M-cone signals. When the S-cone signal is weak, colours
    along the tritan confusion axis are confused; when it is absent, vision along
    that axis is dichromatic. Red-green discrimination is unaffected. Left
    unbound to GO: the nearest process term, GO:0007601 visual perception, is
    broader than S-cone opponent comparison.
  biological_scale: ORGANISM
  evidence:
  - reference: PMID:23022137
    reference_title: "Substitution of isoleucine for threonine at position 190 of S-opsin causes S-cone-function abnormalities."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The performance of subjects with the T190I mutation was significantly
      different from that of normal trichromats along the tritan vector under all
      conditions tested (Mann-Whitney U: p<0.05), but not along the protan or
      deutan vectors.
    explanation: >-
      The discrimination deficit is confined to the tritan axis.
    quote_role: PRIMARY_RESULT
  downstream:
  - target: Tritan Color Vision Defect
    causal_link_type: DIRECT
    description: >-
      A weakened S-cone opponent signal produces tritan colour confusions.
  - target: Tritanopia
    causal_link_type: DIRECT
    description: >-
      An absent S-cone signal leaves dichromatic vision along the tritan axis.
  - target: Abnormal Hardy-Rand-Rittler Tritan Plates
    causal_link_type: DIRECT
    description: >-
      The tritan screening plates detect failures of S-cone opponent
      discrimination.
phenotypes:
- name: Tritan Color Vision Defect
  category: Ophthalmologic
  description: >-
    Impaired discrimination of colours along the blue-yellow (tritan) axis with
    normal red-green discrimination, of variable severity among carriers. Error
    scores on the Farnsworth-Munsell 100-Hue test increase with age, and an
    affected adult reported confusing orange-yellow with pink. A dichromatic
    versus anomalous-trichromatic subdivision is not useful for tritan defects;
    anomalous tritan colour matches have been attributed to rod intrusion.
  notes: >-
    HP:0000552 Tritanomaly is bound for the tritan defect as a whole because HPO
    lists blue-yellow color blindness and blue-yellow dyschromatopsia as its
    exact synonyms; HPO places it under anomalous trichromacy, and the
    dichromatic form is recorded separately below.
  phenotype_term:
    preferred_term: Tritan color vision defect
    term:
      id: HP:0000552
      label: Tritanomaly
    clinical_course: PROGRESSIVE
  evidence:
  - reference: PMID:16961973
    reference_title: "A novel mutation in the short-wavelength-sensitive cone pigment gene associated with a tritan color vision defect."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      made errors on standard color vision tests consistent with the presence of a
      mild tritan color vision deficiency
    explanation: >-
      Mild tritan defect in an L56P heterozygote.
    quote_role: PRIMARY_RESULT
  - reference: PMID:23022137
    reference_title: "Substitution of isoleucine for threonine at position 190 of S-opsin causes S-cone-function abnormalities."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      FM100-Hue error scores increase with increasing age
    explanation: >-
      Within the T190I family, severity rises with age.
    quote_role: PRIMARY_RESULT
  - reference: PMID:17429491
    reference_title: "Adaptive optics retinal imaging reveals S-cone dystrophy in tritan color-vision deficiency."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      He reported that he could not remember having any problems with color vision
      when he was younger, and it was only in recent years that he has experienced
      difficulties with discriminating between some colors such as orange-yellow
      and pink.
    explanation: >-
      Late-recognised, progressive colour confusion reported by a tritanopic
      carrier.
    quote_role: PRIMARY_RESULT
  - reference: PMID:32400513
    reference_title: "Tritan color vision deficiency may be associated with an OPN1SW splicing defect and haploinsufficiency."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      the mutant is associated with tritan color vision deficiency that is mild
      compared to the P264S mutation
    explanation: >-
      The splice allele gives a milder tritan defect than the P264S missense
      allele.
    quote_role: PRIMARY_RESULT
  - reference: PMID:3872255
    reference_title: "The genetics of tritan disturbances."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Evidence is presented that it is--in contradistinction to the
      X-chromosomally inherited red-green defects--incorrect to make a subdivision
      between dichromasia (tritanopia) and anomalous trichromasia (tritanomaly).
    explanation: >-
      Family data argue against splitting tritanopia from tritanomaly.
    quote_role: PRIMARY_RESULT
  - reference: PMID:17429491
    reference_title: "Adaptive optics retinal imaging reveals S-cone dystrophy in tritan color-vision deficiency."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      the anomalous trichromatic tritan phenotype has instead been attributed to
      the involvement of rods in the color match made by tritan subjects
    explanation: >-
      Anomalous tritan matches reflect rod intrusion rather than a shifted S
      pigment.
    quote_role: REVIEW_SYNTHESIS
- name: Tritanopia
  category: Ophthalmologic
  description: >-
    Tritan dichromacy: colour matching and discrimination as if no S-cone class
    were present. Seen in homozygotes and in older or more severely affected
    heterozygotes; many tritans who are dichromatic with a small (1 degree) field
    are not dichromatic with a larger field. HPO has no tritanopia term, so the
    general dichromacy term is bound.
  phenotype_term:
    preferred_term: Tritanopia
    term:
      id: HP:0011518
      label: Dichromacy
  evidence:
  - reference: PMID:17429491
    reference_title: "Adaptive optics retinal imaging reveals S-cone dystrophy in tritan color-vision deficiency."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The father's behavior on all color-vision tests was that of a tritanope.
    explanation: >-
      R283Q carrier with tritan dichromacy.
    quote_role: PRIMARY_RESULT
  - reference: PMID:32400513
    reference_title: "Tritan color vision deficiency may be associated with an OPN1SW splicing defect and haploinsufficiency."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Members of family C who had the P264S and a normal allele had tritanopia
    explanation: >-
      P264S heterozygotes had tritanopia.
    quote_role: BACKGROUND
  - reference: PMID:6977627
    reference_title: "Color matching in autosomal dominant tritan defect."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Eleven tritans were dichromats with 1 degrees field, and only two were
      dichromats with an 8 degrees field.
    explanation: >-
      Dichromacy is field-size dependent in autosomal dominant tritans.
    quote_role: PRIMARY_RESULT
- name: Abnormal Hardy-Rand-Rittler Tritan Plates
  category: Ophthalmologic
  description: >-
    Errors on the tritan screening plates of the Hardy-Rand-Rittler test, which
    separated carriers from non-carriers within one family. Ishihara plates test
    only red-green discrimination and are passed.
  phenotype_term:
    preferred_term: Errors on tritan plates of the Hardy-Rand-Rittler test
    term:
      id: HP:0030587
      label: Abnormal Hardy-Rand-Rittler plate test
  evidence:
  - reference: PMID:23022137
    reference_title: "Substitution of isoleucine for threonine at position 190 of S-opsin causes S-cone-function abnormalities."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Members of the family with the T190I mutation all fail the tritan plates on
      HRR pseudo-isochromatic plates, and members of the family who lack the
      mutation pass the tritan plates
    explanation: >-
      HRR tritan plate failure segregates with the T190I variant.
    quote_role: PRIMARY_RESULT
  - reference: PMID:17429491
    reference_title: "Adaptive optics retinal imaging reveals S-cone dystrophy in tritan color-vision deficiency."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      He made tritan errors on the HRR pseudoisochromatic plates, the Lanthony's
      desaturated D15, and the Farnsworth D15
    explanation: >-
      The R283Q tritanope failed the HRR tritan plates.
    quote_role: PRIMARY_RESULT
- name: Reduced or Absent S-Cone Electroretinogram
  category: Ophthalmologic
  description: >-
    The S-cone (blue cone) ERG, recorded with strong yellow adaptation, is reduced
    or unrecordable in tritanopes, while it is normal in dominant optic atrophy,
    which can also produce tritan errors. One pedigree also showed negative
    bright-flash responses that its authors read as L- and M-cone involvement.
  phenotype_term:
    preferred_term: Reduced or absent S-cone electroretinogram
    term:
      id: HP:0008275
      label: Abnormal light-adapted electroretinogram
  evidence:
  - reference: PMID:3876823
    reference_title: "Differential diagnosis of congenital tritanopia and dominantly inherited juvenile optic atrophy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The blue cone ERG confirmed a difference between the two groups; it was
      unrecordable in the patients with congenital tritanopia but within the
      normal range in those with DIJOA.
    explanation: >-
      Blue cone ERG unrecordable in congenital tritanopia.
    quote_role: PRIMARY_RESULT
  - reference: PMID:3485517
    reference_title: "The electroretinographic characteristics of congenital tritan defects."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Compared with the response of normal subjects, a marked reduction or a lack
      of the blue cone responses was clearly shown in the spectral response
      patterns of tritanopes.
    explanation: >-
      Spectral ERG shows reduced or absent blue cone responses.
    quote_role: PRIMARY_RESULT
  - reference: PMID:3485517
    reference_title: "The electroretinographic characteristics of congenital tritan defects."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Electroretinograms elicited by strong white stimulation or xenon flashes
      showed negative responses (a-waves larger than b-waves) with normal rod
      function in each tritanopic subject.
    explanation: >-
      A single pedigree also had negative bright-flash ERGs, which the authors
      read as L- and M-cone involvement.
    quote_role: PRIMARY_RESULT
genetic:
- name: OPN1SW
  association: Genetic Mutation
  relationship_type: CAUSATIVE
  gene_term:
    preferred_term: OPN1SW
    term:
      id: hgnc:1012
      label: OPN1SW
  inheritance:
  - name: Autosomal dominant
  notes: >-
    Heterozygous missense variants and one intron 3 splice-donor deletion. The
    authors of the T190I report state that every amino acid substitution in OPN1SW
    observed to date has been disease causing. Family C of the original P264S
    study segregated both P264S and the intron 3 deletion; the deletion was first
    judged not to cause tritanopia and was later shown to disrupt splicing and to
    segregate with a mild tritan defect in another family. No ClinGen
    gene-disease validity assertion is recorded here; none was looked up.
  evidence:
  - reference: PMID:1531728
    reference_title: "Human tritanopia associated with two amino acid substitutions in the blue-sensitive opsin."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      to detect in four of nine unrelated tritanopic subjects two different point
      mutations in the gene encoding the blue-sensitive opsin, each leading to an
      amino acid substitution
    explanation: >-
      OPN1SW missense variants found in tritanopic probands.
    quote_role: PRIMARY_RESULT
  - reference: PMID:23022137
    reference_title: "Substitution of isoleucine for threonine at position 190 of S-opsin causes S-cone-function abnormalities."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      All mutations in the OPN1SW gene that result in an amino acid substitution
      that have been observed to date are disease causing
    explanation: >-
      Authors' summary that all reported OPN1SW substitutions cause tritan
      defects.
    quote_role: PRIMARY_RESULT
  variants:
  - name: p.Leu56Pro (L56P)
    type: missense
    description: >-
      Found heterozygous in a 30-year-old man with a mild tritan defect; absent
      from 564 control OPN1SW genes.
    evidence:
    - reference: PMID:16961973
      reference_title: "A novel mutation in the short-wavelength-sensitive cone pigment gene associated with a tritan color vision defect."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        He was found to be heterozygous for a mutation that caused the amino acid
        proline to be substituted in place of a highly conserved leucine at amino
        acid position 56 in the S cone opsin.
      explanation: >-
        Identifies L56P in a tritan proband.
      quote_role: PRIMARY_RESULT
  - name: p.Gly79Arg (G79R)
    type: missense
    description: >-
      One of the two substitutions found in the founding genotype study of
      tritanopia. Also found in a sister and father in a Japanese family
      segregating homozygous PDE6C achromatopsia, where the authors suggested it
      might explain the sister's complete rather than incomplete achromatopsia.
    evidence:
    - reference: PMID:25605338
      reference_title: "Congenital Achromatopsia and Macular Atrophy Caused by a Novel Recessive PDE6C Mutation (p.E591K)."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        We also identified an OPN1SW mutation (p.G79R), which is associated with
        congenital tritan deficiencies, in the sister and the father but not in
        the brother.
      explanation: >-
        G79R observed in a second, unrelated family; the possible modifier effect
        on achromatopsia severity is the authors' suggestion only.
      quote_role: PRIMARY_RESULT
    - reference: PMID:23022137
      reference_title: "Substitution of isoleucine for threonine at position 190 of S-opsin causes S-cone-function abnormalities."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Five mutations in the S-cone-opsin gene (OPN1SW) that give rise to
        different single amino-acid substitutions (L56P, G79R, S214P, P264S,
        R283Q) are known to be associated with tritan color-vision deficiency.
      explanation: >-
        Lists G79R among the tritan-associated OPN1SW substitutions.
      quote_role: BACKGROUND
  - name: p.Thr190Ile (T190I)
    type: missense
    description: >-
      Segregates with tritan errors in one family (nine heterozygous relatives);
      the only reported variant in extracellular loop II rather than a
      transmembrane helix.
    evidence:
    - reference: PMID:23022137
      reference_title: "Substitution of isoleucine for threonine at position 190 of S-opsin causes S-cone-function abnormalities."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Affected family members were heterozygous for a nucleotide change that
        substituted the amino acid isoleucine (I) in place of threonine (T) that is
        normally present at position 190 of the S-opsin.
      explanation: >-
        Identifies T190I in affected relatives.
      quote_role: PRIMARY_RESULT
  - name: p.Ser214Pro (S214P)
    type: missense
    description: >-
      The second substitution found in the founding genotype study of tritanopia.
    evidence:
    - reference: PMID:23022137
      reference_title: "Substitution of isoleucine for threonine at position 190 of S-opsin causes S-cone-function abnormalities."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Five mutations in the S-cone-opsin gene (OPN1SW) that give rise to
        different single amino-acid substitutions (L56P, G79R, S214P, P264S,
        R283Q) are known to be associated with tritan color-vision deficiency.
      explanation: >-
        Lists S214P among the tritan-associated OPN1SW substitutions.
      quote_role: BACKGROUND
  - name: p.Pro264Ser (P264S)
    type: missense
    description: >-
      Associated with tritanopia in heterozygotes; reported separately as a third
      tritan substitution.
    evidence:
    - reference: PMID:32400513
      reference_title: "Tritan color vision deficiency may be associated with an OPN1SW splicing defect and haploinsufficiency."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Members of family C who had the P264S and a normal allele had tritanopia
      explanation: >-
        P264S heterozygotes had tritanopia.
      quote_role: BACKGROUND
  - name: p.Arg283Gln (R283Q)
    type: missense
    description: >-
      Heterozygous in a father with tritanopia and in his two children, who had a
      mild defect or none detected on standard tests; adaptive optics showed absent
      S cones in the father.
    evidence:
    - reference: PMID:17429491
      reference_title: "Adaptive optics retinal imaging reveals S-cone dystrophy in tritan color-vision deficiency."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        All 29 control subjects were homozygous for arginine.
      explanation: >-
        R283Q was absent from the 29 controls sequenced alongside the family.
      quote_role: PRIMARY_RESULT
  - name: OPN1SW intron 3 +5G deletion (exon 3 splice donor)
    type: splice donor variant
    description: >-
      Deletion of the G five nucleotides into intron 3, disrupting the exon 3
      splice donor; in vitro it yields only a transcript lacking exons 2 and 3,
      with a frameshift and premature stop. Heterozygotes in one family had a mild
      tritan defect.
    evidence:
    - reference: PMID:32400513
      reference_title: "Tritan color vision deficiency may be associated with an OPN1SW splicing defect and haploinsufficiency."
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: >-
        Direct sequencing of this product revealed that it represents a single
        isoform that lacks exons 2 and 3, and contains exon 1, 4 and 5 spliced
        together
      explanation: >-
        Splicing assay shows the allele yields only an exon 2-3 skipped transcript.
      quote_role: PRIMARY_RESULT
diagnosis:
- name: Tritan-sensitive colour vision testing
  description: >-
    Tests with a tritan axis (Hardy-Rand-Rittler tritan plates, Farnsworth-Munsell
    100-Hue, Lanthony desaturated D15, Cambridge Colour Test, Moreland
    anomaloscope) detect the defect. Ishihara plates test only red-green
    discrimination and are passed. Mild defects in young carriers can be missed
    under standard photopic conditions and become evident at low luminance.
  diagnosis_term:
    preferred_term: colour vision testing
    term:
      id: NCIT:C156778
      label: Vision Assessment
  evidence:
  - reference: PMID:17429491
    reference_title: "Adaptive optics retinal imaging reveals S-cone dystrophy in tritan color-vision deficiency."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      He made no errors on the Ishihara pseudoisochromatic plates, nor on the
      Medmont C100
    explanation: >-
      A tritanope passed the Ishihara plates, which do not test the tritan axis.
    quote_role: PRIMARY_RESULT
  - reference: PMID:23022137
    reference_title: "Substitution of isoleucine for threonine at position 190 of S-opsin causes S-cone-function abnormalities."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      the tritan color-vision deficiency associated with the T190I mutation may
      indeed go unnoticed if younger subjects only are tested with the FM100-Hue
      test
    explanation: >-
      Standard photopic testing can miss mild defects in young carriers.
    quote_role: PRIMARY_RESULT
- name: S-cone electroretinography
  description: >-
    The blue cone ERG is reduced or unrecordable in tritanopes and separates
    congenital tritan defects from dominant optic atrophy.
  diagnosis_term:
    preferred_term: S-cone electroretinography
    term:
      id: NCIT:C101217
      label: Retinal Examination
  evidence:
  - reference: PMID:3876823
    reference_title: "Differential diagnosis of congenital tritanopia and dominantly inherited juvenile optic atrophy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We believe that congenital tritanopia and DIJOA are distinct disease
      entities and that the blue cone ERG is a key factor in the differential
      diagnosis.
    explanation: >-
      Recommends the blue cone ERG for differential diagnosis.
    quote_role: PRIMARY_RESULT
- name: OPN1SW sequencing
  description: >-
    Sequencing the coding exons and flanking intron sequence of OPN1SW identifies
    the causal variant and allows testing of relatives, who may be mildly
    affected or unaware of a defect.
  diagnosis_term:
    preferred_term: Genetic Testing
    term:
      id: NCIT:C15709
      label: Genetic Testing
  evidence:
  - reference: PMID:16961973
    reference_title: "A novel mutation in the short-wavelength-sensitive cone pigment gene associated with a tritan color vision defect."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We tested the hypothesis that his color vision impairment was due to a
      mutation in the S cone photopigment gene.
    explanation: >-
      OPN1SW sequencing was used to identify the cause of a tritan defect.
    quote_role: PRIMARY_RESULT
differential_diagnoses:
- name: Autosomal dominant optic atrophy
  description: >-
    Dominantly inherited juvenile optic atrophy also produces tritan errors and was
    once thought to be the same entity as congenital tritanopia.
  disease_term:
    preferred_term: autosomal dominant optic atrophy
    term:
      id: MONDO:0008134
      label: autosomal dominant optic atrophy, classic form
  distinguishing_features:
  - Blue cone ERG within the normal range.
  - Optic atrophy, which can be ruled out in tritan pedigrees.
  evidence:
  - reference: PMID:3876823
    reference_title: "Differential diagnosis of congenital tritanopia and dominantly inherited juvenile optic atrophy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The blue cone ERG confirmed a difference between the two groups; it was
      unrecordable in the patients with congenital tritanopia but within the
      normal range in those with DIJOA.
    explanation: >-
      The blue cone ERG distinguishes the two conditions.
    quote_role: PRIMARY_RESULT
  - reference: PMID:6606981
    reference_title: "Tritan pedigree without optic-nerve atrophy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This report describes the results of testing 34 members of a pedigree
      (including four tritans) for whom optic atrophy can be ruled out
    explanation: >-
      A tritan pedigree without optic atrophy shows the two are separable.
    quote_role: PRIMARY_RESULT
- name: Blue cone monochromacy
  description: >-
    X-linked loss of L- and M-cone function in which S cones remain; the reverse
    of the tritan defect despite the similar name.
  disease_term:
    preferred_term: blue cone monochromacy
    term:
      id: MONDO:0010563
      label: blue cone monochromacy
  distinguishing_features:
  - X-linked inheritance.
  - L- and M-cone function absent while S-cone function is retained.
  evidence:
  - reference: PMID:15312026
    reference_title: "Molecular genetics of colour vision deficiencies."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Blue cone monochromacy is a rare form of colour vision deficiency that
      results from mutations that abolish function of both the L and M pigment
      genes.
    explanation: >-
      Defines blue cone monochromacy as loss of L and M pigment function.
    quote_role: REVIEW_SYNTHESIS
- name: Autosomal dominant cone dystrophy with early tritanopia (16q12 IRXB duplication)
  description: >-
    Tandem duplications of the IRXB gene cluster (IRX5, IRX6) on chromosome 16q12
    cause an autosomal dominant progressive cone dystrophy whose earliest sign is
    a tritan colour vision defect, so the inheritance pattern and the first
    colour vision finding mimic the OPN1SW disorder. No specific MONDO term was
    found, so the general cone dystrophy term is bound.
  disease_term:
    preferred_term: autosomal dominant cone dystrophy with early tritanopia
    term:
      id: MONDO:0000455
      label: cone dystrophy
  distinguishing_features:
  - Progressive cone dystrophy with declining visual acuity and central vision loss.
  - Copy-number gain at 16q12 rather than an OPN1SW sequence variant.
  evidence:
  - reference: PMID:33891002
    reference_title: "A duplication on chromosome 16q12 affecting the IRXB gene cluster is associated with autosomal dominant cone dystrophy with early tritanopic color vision defect."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      All patients presented with a unique progressive cone dystrophy phenotype
      hallmarked by early tritanopic color vision defects.
    explanation: >-
      A dominant cone dystrophy that begins with tritan defects is a genetic
      phenocopy of the early OPN1SW phenotype.
    quote_role: PRIMARY_RESULT
animal_models:
- name: Opn1sw Neo/Neo S-opsin-null mouse
  species: Mouse (Mus musculus)
  genotype: Opn1sw(Neo/Neo), neomycin cassette inserted between exons 3 and 4 of Opn1sw
  publication: PMID:21219924
  description: >-
    Mouse lacking S-opsin expression. It is not a model of a human tritan allele:
    it carries no missense or splice variant and is homozygous null, and most
    mouse cones co-express M and S opsin. It is recorded because its cones survive
    without S-opsin, which bears on the mechanism of S-cone loss.
  modeled_mechanisms:
  - target: Progressive S-Cone Degeneration
    relationship: FAILS_TO_RECAPITULATE
    fidelity: LOW
    model_scale: CELLULAR
    description: >-
      Cones lacking S-opsin remain viable for at least 1.5 years, so loss of
      S-opsin alone does not reproduce S-cone death.
    limitations: >-
      A null allele cannot test the proposed dominant-negative toxicity of a
      mutant human S-opsin, and mouse cones that co-express M opsin are not
      equivalent to human S cones, which express S opsin alone.
    divergences:
    - divergence_type: CAUSE_UNREPRESENTED
      materiality: QUALIFYING
      description: >-
        The human lesion is a heterozygous missense or splice allele; the mouse
        has no S-opsin at all, so a toxic mutant protein, the proposed cause of
        S-cone death, is absent.
    - divergence_type: SPECIES_MISMATCH
      materiality: QUALIFYING
      description: >-
        Most mouse cones co-express M and S opsin in dorso-ventral gradients,
        whereas the human S cone expresses only S opsin, so a mouse cone losing
        S-opsin keeps a photopigment and the human S cone would not.
    evidence:
    - reference: PMID:21219924
      reference_title: "A mouse M-opsin monochromat: retinal cone photoreceptors have increased M-opsin expression when S-opsin is knocked out."
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: >-
        cones of the Opn1sw(Neo/Neo) mouse remain viable for at least 1.5 yrs,
        even though many ventral cones do not form outer segments
      explanation: >-
        S-opsin-null cones survive long term.
      quote_role: PRIMARY_RESULT
    - reference: PMID:21219924
      reference_title: "A mouse M-opsin monochromat: retinal cone photoreceptors have increased M-opsin expression when S-opsin is knocked out."
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: >-
        Most C57Bl/6 mouse cones co-express both opsins, but in dorso-ventral
        counter-gradients, with M-opsin dominant in the dorsal retina and S-opsin
        in the ventral retina, and S-opsin 4-fold greater overall.
      explanation: >-
        Documents the opsin co-expression that limits the model.
      quote_role: BACKGROUND

📚

References & Deep Research

Deep Research

1

Deep research results are used as seeds for research; they do not undergo the same validation as the main records and may contain errors. How we use deep research.

Evaluations and curation notes (1)

Create: Tritan_Color_Vision_Deficiency · 2026-10-14T21:25:17Z · View source

Created the autosomal dominant tritan colour vision deficiency entry (MONDO:0008610, blue color blindness; OPN1SW, hgnc:1012) from the curation stub stubs/Blue_Color_Blindness.yaml, which this change deletes. The entry covers the whole inherited tritan series; acquired tritan defects are out of scope, and tritanopia and tritanomaly are not split into subtypes because family data (PMID:3872255) and the rod-intrusion explanation of anomalous tritan matches (PMID:17429491) argue against that subdivision. Content: autosomal dominant inheritance with incomplete penetrance and variable expressivity; two screening-based prevalence records; seven OPN1SW variants (L56P, G79R, T190I, S214P, P264S, R283Q and the intron 3 +5G splice-donor deletion); a seven-node causal chain from the heterozygous OPN1SW variant through two competing branches (misfolded mutant opsin leading to progressive S-cone degeneration, recorded as an emerging dominant-negative hypothesis; and halved S-opsin dosage from the splice allele, recorded as an emerging haploinsufficiency hypothesis) that converge on reduced S-cone signal and loss of the blue-yellow opponent signal; four phenotypes (tritan colour vision defect, tritanopia, HRR tritan plate errors, reduced S-cone ERG), all causally connected; diagnosis (tritan-sensitive colour testing, S-cone ERG, OPN1SW sequencing); three differential diagnoses (dominant optic atrophy, blue cone monochromacy, the 16q12 IRXB-duplication cone dystrophy with early tritanopia); and the S-opsin-null mouse recorded as FAILS_TO_RECAPITULATE for S-cone degeneration. No treatment section: no disease-specific treatment was found. No GeneReviews chapter exists (check-genereviews --online: NO_CHAPTER). Deep research: one OpenScientist report (research/Tritan_Color_Vision_Deficiency-deep-research-openscientist.md). Reference validation 11/11 resolved, 0 off topic; preflight-dr PASS (OPN1SW mentioned 33 times, OMIM 190900 matches). Term validation flagged mislabelled or wrong suggestions that were not used: HP:0000496 (the report's 'Abnormality of color vision' is Abnormality of eye movement), UBERON:0001782 (pigmented layer of retina, not the photoreceptor layer), and CL:0000573 offered for S cones where CL:0003050 S cone cell is the specific term. The report describes the disorder as congenital, stationary and non-degenerative, inferring this from S-opsin-null mouse cone survival; that conflicts with the human adaptive optics study (PMID:17429491, not cited by the report), the T190I family age data and the 2026 review it does cite (PMID:42346125, which says progressive tritanopia), so the entry records a progressive course and the mouse as not recapitulating degeneration. Report citations used: PMID:23022137, 32400513, 42346125, 40769301, 21219924, 25605338, 33891002. Not used: PMID:41317340 (acquired tritan defects in multiple sclerosis, out of scope), PMID:38060327 (cone opsin gene therapy in a blue cone monochromacy model, not a tritan treatment), PMID:30443703 (quality of life in colour vision deficiency generally, not tritan-specific), PMID:15094734 (blue cone monochromacy testing). Most primary evidence came from PubMed searches outside the report (Weitz 1992, Gunther 2006, Baraas 2007, Went and Pronk 1985, Miyake 1985, Shinzato 1986, Pokorny 1981, Padmos 1978, Higgins 1983, Curcio 1991, Deeb 2004). The original P264S paper (PMID:1386496) and six early pedigree papers had no abstract or full text on retrieval and are named in notes rather than cited. Validation: just validate, validate-terms, count-verified-snippets (all snippets verified), check-entity-refs, check-causal-targets, check-duplicate-keys, check-enum-values, check-block-scalar-comments and the whole-KB offline gates passed; validate-disorders run before commit.

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Tritan Color Vision Deficiency (MONDO:0008610): Comprehensive Disease Characteristics Report

openscientist-autonomous 8 citations 2026-10-14T21:02:54.791696

Tritan Color Vision Deficiency (MONDO:0008610): Comprehensive Disease Characteristics Report

Summary

Tritan Color Vision Deficiency (tritan CVD; MONDO:0008610; OMIM 190900) is a rare, congenital, autosomal dominant disorder of the blue-yellow (short-wavelength) axis of color vision. It is caused by heterozygous mutations in OPN1SW, the single autosomal gene on chromosome 7q32.1 that encodes the short-wavelength-sensitive (S) cone opsin (HGNC:1012; UniProt P03999). Because OPN1SW — unlike the tandemly arranged X-linked L/M opsin genes (OPN1LW/OPN1MW) — is a solitary autosomal gene, a single pathogenic allele is sufficient to disrupt S-cone function, giving the disorder its autosomal dominant inheritance pattern and roughly equal sex distribution. Pathogenic missense alleles (L56P, G79R, S214P, P264S, R283Q, T190I) are thought to cause S-opsin misfolding/dysfunction, while splice-disrupting variants act through haploinsufficiency, producing a reduced or absent S-cone signal and selective loss of blue-yellow discrimination.

Clinically, tritan CVD is benign, stationary, and non-degenerative. Affected individuals have normal visual acuity, a normal fundus, and normal protan/deutan (red-green) color discrimination; the defect is confined to the tritan (blue-yellow) vector and is detected by color-vision psychophysics such as the Farnsworth-Munsell 100-hue, D-15, Mollon-Reffin Minimal test, and computerized tests (Cambridge Colour Test, CAD). Congenital tritan is the rarest of the congenital color vision deficiencies, in sharp contrast to acquired tritan defects, which are the most common pattern of acquired color vision loss (seen in glaucoma, diabetic retinopathy, multiple sclerosis, and normal aging owing to the selective vulnerability of the S-cone/short-wavelength pathway). The disorder shows incomplete penetrance and markedly variable expressivity — one allele (T190I) produces an illuminance-dependent phenotype ranging from mild tritanomaly to full tritanopia within a single genotype.

There is no disease-modifying therapy for congenital tritan CVD. Management is entirely supportive (education, occupational counseling, color-filter/assistive aids) together with genetic counseling for autosomal dominant inheritance. Because the condition does not affect survival, acuity, or cause ocular complications, the prognosis is excellent. The principal animal model — the Opn1sw knockout (Opn1sw^Neo/Neo) mouse — confirms that S-opsin-deficient cones remain viable for at least 1.5 years without degeneration, establishing that S-cones are a theoretically rescuable target. AAV-mediated cone-opsin gene augmentation has restored cone structure and function in related blue cone monochromacy models, providing translational proof-of-concept for a future S-opsin gene therapy, although no tritan-specific clinical trials exist.

1. Disease Information

Overview. Tritan Color Vision Deficiency is an inherited abnormality of the blue-yellow axis of color perception caused by dysfunction of the short-wavelength-sensitive (S) cone photoreceptors. The spectrum ranges from tritanomaly (reduced but present S-cone function; anomalous trichromacy on the tritan axis) to tritanopia (complete loss of S-cone function; dichromacy). It is sometimes described as "blue-yellow color blindness."

Key identifiers.

Resource	Identifier
MONDO	MONDO:0008610
OMIM	190900 (Tritanopia / Colorblindness, tritan)
Gene (HGNC)	OPN1SW, HGNC:1012
UniProt	P03999 (OPN1SW / Blue-sensitive opsin)
MeSH	Color Vision Defects / Tritanopia
ICD-10	H53.59 (Other color vision deficiencies)

Synonyms / alternative names: Tritanopia, Tritanomaly, Blue-yellow color blindness, Tritan defect, Colorblindness (tritan), S-cone color vision deficiency.

Information source type: Information is derived predominantly from aggregated disease-level resources (OMIM, Orphanet, HPO) and from small clinical pedigree / psychophysical case studies rather than from large EHR-based individual-patient cohorts. Because the congenital form is rare and benign, it is under-ascertained in the general population; much of the molecular evidence derives from a handful of families and from model organisms.

2. Etiology

Disease causal factors. Congenital tritan CVD is a Mendelian genetic disorder caused by heterozygous mutations in the OPN1SW gene (chromosome 7q32.1), which encodes the S-cone opsin. There is no infectious or environmental cause for the congenital form. (See Finding F001.)

Genetic risk factors. The causal variants are pathogenic alleles of OPN1SW. At least six recognized pathogenic missense substitutions are associated with tritan deficiency:

Variant	Note
L56P	Classic tritan allele
G79R	Classic tritan allele; also observed co-segregating in a PDE6C achromatopsia family
S214P	Classic tritan allele
P264S	Classic tritan allele
R283Q	Classic tritan allele
T190I	Illuminance-dependent phenotype (mild tritan → tritanope)

In addition, splice-disrupting OPN1SW variants cause tritan deficiency via haploinsufficiency (Finding F002). Because OPN1SW is a single autosomal gene (not part of a head-to-tail tandem array like the X-linked L/M opsins), a single mutant allele is sufficient to produce the phenotype — hence autosomal dominant inheritance.

Environmental / acquired risk factors. The congenital disorder has no environmental trigger. However, acquired tritan defects (phenotypically similar blue-yellow loss) are common and are driven by preferential short-wavelength-pathway vulnerability in glaucoma, primary angle closure, diabetic retinopathy, macular telangiectasia type II, multiple sclerosis, HIV retinopathy, and normal aging (Finding F003). These are distinct in etiology from the Mendelian OPN1SW disorder but important for differential diagnosis.

Protective factors. No genetic or environmental protective factors are established for congenital tritan CVD. (Information not available.)

Gene-environment interactions. For the T190I allele, retinal illuminance (an environmental/testing variable) interacts with genotype to determine severity: the same genotype behaves as mild tritanomaly at higher illuminance but as full tritanopia at low illuminance (Finding F002). This is the clearest documented gene-environment (gene × light-level) interaction for this disorder.

3. Phenotypes

The defining phenotype is selective impairment of blue-yellow (tritan-axis) color discrimination with sparing of all other visual functions (Finding F005).

Phenotype	Type	Onset	Severity	Progression	Frequency	HPO term
Tritan (blue-yellow) discrimination loss	Clinical sign / lab abnormality	Congenital	Mild (tritanomaly) → severe (tritanopia); variable	Stationary	Defining feature (100%)	HP:0000552 (Tritanomaly)
Abnormal color vision	Clinical sign	Congenital	Variable	Stationary	100%	HP:0000551 / HP:0000496
Normal visual acuity	(Preserved)	—	—	—	Typical	—
Normal fundus	(Preserved)	—	—	—	Typical	—

Phenotype characteristics. Onset is congenital; severity is variable (mild tritanomaly to complete tritanopia), including within a single family and even illuminance-dependent for the T190I allele; progression is stable/stationary (non-degenerative). Red-green (protan/deutan) discrimination, visual acuity, and the retinal fundus are normal, which distinguishes tritan CVD from the progressive cone dystrophies that can begin with tritan-like defects.

Quality of life impact. Congenital tritan is typically mild and many individuals are undiagnosed. Color vision deficiency broadly causes documented difficulties in daily activities, education, career choice, and emotional well-being (Finding F005), but the tritan subtype is generally less disabling than red-green defects for everyday red-green-coded tasks. Impact is best characterized at the level of "color vision deficiency" generally rather than tritan-specifically.

Suggested HPO terms: HP:0000552 (Tritanomaly), HP:0000551 (Abnormality of color vision), HP:0000496 (Abnormality of color vision), and HP:0000496/HP:0000551 for abnormal color vision generally.

4. Genetic / Molecular Information

Causal gene. OPN1SW (opsin 1, short-wave-sensitive), chromosome 7q32.1; HGNC:1012; UniProt P03999; OMIM gene/phenotype 190900. Encodes the S-cone opsin, a G-protein-coupled receptor (GPCR) of the visual-pigment family that, with 11-cis-retinal as chromophore, forms the short-wavelength-sensitive photopigment of S-cones (Finding F001).

Pathogenic variants. - Affected gene: OPN1SW (HGNC:1012). - Variant classification: The classic missense alleles (L56P, G79R, S214P, P264S, R283Q, T190I) are pathogenic/likely pathogenic for autosomal dominant tritan deficiency per co-segregation and functional data. - Variant type/class: Predominantly missense substitutions; also splice-site variants acting through haploinsufficiency. - Functional consequences: Missense variants are inferred to cause S-opsin misfolding / loss of function (dominant through reduced functional S-opsin), while splice variants cause haploinsufficiency (Finding F002). The T190I allele produces a dosage/light-dependent partial loss of function. - Allele frequency: These are rare variants; precise gnomAD frequencies are not well established for the congenital tritan alleles (Information limited). - Somatic vs germline: Germline.

Modifier genes. No formal modifier genes are established. Co-occurrence of an OPN1SW G79R allele was proposed to modify the phenotype (complete vs incomplete achromatopsia) in a family also segregating a recessive PDE6C mutation, suggesting OPN1SW status can modulate cone phenotype in trans with other cone-gene lesions (a modifier-like effect; PMID:25605338).

Epigenetic information. No disease-specific epigenetic changes are documented for tritan CVD. Cone opsin expression is transcriptionally controlled by nuclear receptors TRβ2 (THRB), RXRγ, RORβ, RORα, and the homeobox factor CRX (Finding F004), but these are developmental regulators, not established epigenetic disease mechanisms.

Chromosomal abnormalities. None for the single-gene OPN1SW disorder. Of note, a distinct autosomal dominant cone dystrophy with early tritanopic color defect maps to a 16q12 duplication affecting the IRXB/IRX5-IRX6 cluster (PMID:33891002) — this is a separate progressive disease, not OPN1SW tritan CVD.

5. Environmental Information

Environmental factors: None cause the congenital disorder. Acquired tritan-type defects arise secondarily to toxic, metabolic, and degenerative retinal/optic-nerve insults (see §2 and §3).
Lifestyle factors: Not applicable to congenital tritan CVD.
Infectious agents: Not applicable to the congenital genetic disorder. (HIV retinopathy can produce acquired cone dysfunction with downregulation of OPN1SW and other cone transcripts, but this is a secondary, acquired phenomenon, not congenital tritan CVD.)

6. Mechanism / Pathophysiology

Ordered causal chain

A heterozygous OPN1SW mutation (missense, e.g., L56P/G79R/S214P/P264S/R283Q/T190I, or a splice-site variant) is inherited in autosomal dominant fashion → leads to an abnormal or reduced-quantity S-cone opsin protein.
Missense branch: The amino-acid substitution leads to misfolding / impaired function of the S-opsin GPCR (inferred from GPCR structural biology; direct structural proof for each tritan allele is limited) → results in reduced functional short-wavelength photopigment in S-cones. Splice branch: The splice-disrupting variant leads to loss of one functional allele's product (haploinsufficiency) → results in reduced S-opsin quantity (Finding F002).
Reduced/abnormal S-opsin results in a diminished or absent S-cone photoreceptor light response (phototransduction signal) along the short-wavelength pathway.
Loss of the S-cone signal leads to impaired coding of the blue-yellow (koniocellular/S-cone-opponent) chromatic channel downstream.
This results in the clinical manifestation: selective loss of blue-yellow (tritan-axis) color discrimination, with preserved acuity, red-green discrimination, and normal fundus (Finding F005).
Because S-cones (unlike rods) remain viable without their opsin (demonstrated in the Opn1sw^Neo/Neo mouse, Finding F004), the phenotype is stationary and non-degenerative — the chain does not progress to photoreceptor death or vision loss.

For the T190I allele, step 2 is partial and illuminance-modulated: at higher retinal illuminance enough functional S-opsin signal remains for mild tritanomaly, whereas at low illuminance the signal falls below threshold and the phenotype becomes full tritanopia (Finding F002).

Mechanistic detail by category

Molecular pathways: Visual phototransduction (GPCR/opsin → transducin → cGMP phosphodiesterase → CNG channel) specifically in the S-cone. The primary lesion is at the receptor (opsin) step. GO: phototransduction (GO:0007602), detection of light stimulus involved in visual perception (GO:0050908).
Cellular processes: Reduced S-cone light response; notably no apoptosis/degeneration (cones survive). GO: visual perception (GO:0007601), photoreceptor cell maintenance.
Protein dysfunction: S-opsin misfolding / loss of function (missense) or reduced quantity (haploinsufficiency). GO: photoreceptor outer segment (GO:0001750).
Metabolic changes: None established; the chromophore is 11-cis-retinal (CHEBI:16066).
Immune involvement: None.
Tissue damage mechanisms: None in the congenital disorder (benign, stationary).
Biochemical abnormalities: Defective short-wavelength photopigment function.
Molecular profiling: In the mouse model, elimination of S-opsin mRNA relieves translational competition, increasing M-opsin expression in affected cones — a compensatory shift (Finding F004).

Cell type involved: S-cone photoreceptor (CL:0000573, retinal cone cell / short-wavelength-sensitive cone). Biological process GO terms: GO:0007602 (phototransduction), GO:0007601 (visual perception), GO:0050908 (detection of light stimulus in visual perception).

7. Anatomical Structures Affected

Organ level (primary): Eye — specifically the retina (UBERON:0000966). Body system: visual/nervous system. No secondary organ involvement.
Tissue/cell level: Neural retina (UBERON:0003902); specific target cell population = S-cone photoreceptors (CL:0000573, cone retinal photoreceptor cell). Rods, L-cones, and M-cones are spared.
Subcellular level: The photoreceptor outer segment (GO:0001750), where opsin-based phototransduction occurs; the S-opsin is a membrane protein of the outer-segment disc membranes. In the mouse model, many S-opsin-null ventral cones fail to form outer segments (Finding F004).
Localization: Bilateral and symmetric (both eyes equally, as expected for a germline opsin gene defect). UBERON:0000966 (retina), UBERON:0001782 (retinal photoreceptor layer).
Lateralization: Bilateral, symmetric.

8. Temporal Development

Onset: Congenital (present from birth), though frequently detected only when color vision is formally tested in later childhood or adulthood. Onset pattern: non-progressive/congenital.
Progression: Stationary — stable and non-progressive over life. No disease stages. This is supported both clinically and by the animal model, in which S-opsin-null cones survive ≥1.5 years without degeneration (Finding F004).
Disease course: Chronic lifelong but benign and unchanging.
Remission patterns: Not applicable (stable congenital trait; no remission, no worsening).
Critical periods: Not applicable; because cones remain viable long-term, any hypothetical gene-replacement window would be broad (a favorable feature for future therapy).

9. Inheritance and Population

Epidemiology. Congenital tritan CVD is the rarest congenital color vision deficiency (Finding F003). A 2025 systematic review/meta-analysis (1,703,619 participants; 56 studies; 21 countries) estimated the global prevalence of all congenital CVD at 2.59% (95% CI 2.20–3.03%), overwhelmingly red-green (deutan/protan); tritan is the smallest subtype. Classic textbook estimates place tritan prevalence on the order of ~1 in 10,000 or lower, but precise congenital tritan prevalence figures are uncertain owing to under-ascertainment.

Inheritance. Autosomal dominant (OPN1SW is a single autosomal gene on 7q32.1), with: - Penetrance: Incomplete. - Expressivity: Variable — ranging from mild tritanomaly to tritanopia, even illuminance-dependent for T190I (Finding F002). - Genetic anticipation: Not applicable (not a repeat-expansion disorder). - Germline mosaicism / founder effects / consanguinity: Not established as relevant; as an autosomal dominant single-gene trait, consanguinity is not a driver. - Carrier frequency: Not well defined (rare alleles).

Population demographics. - Sex ratio: Approximately 1:1 (autosomal), in contrast to the strong male predominance of X-linked red-green CVD. - Affected populations / geographic distribution: No strong ethnic or geographic enrichment is established for congenital tritan CVD. (Information limited.)

10. Diagnostics

Clinical/psychophysical color-vision tests (primary diagnostic modality). Diagnosis rests on demonstrating a selective tritan-axis defect (Finding F005):

Test	Role in tritan diagnosis
Farnsworth-Munsell 100-hue	Blue-yellow confusion axis errors
Farnsworth D-15 / Lanthony D-15	Tritan confusion axis crossings
Hardy-Rand-Rittler (HRR) plates	Includes tritan plates
Mollon-Reffin Minimal test	Sensitive color-discrimination test for tritan axis
Cambridge Colour Test (CCT)	Computerized; quantifies tritan vector threshold
Colour Assessment and Diagnosis (CAD)	Quantifies tritan vector; high sensitivity/specificity
Anomaloscope (Moreland equation)	Tritan/blue-green matching

Electrophysiology: S-cone-specific ERG can demonstrate selective S-cone dysfunction; standard full-field ERG and acuity are otherwise normal, helping distinguish stationary tritan CVD from cone dystrophies.

Genetic testing: Single-gene OPN1SW sequencing (including splice-site analysis) confirms the molecular diagnosis; WES/WGS or inherited-retinal-disease gene panels including OPN1SW are appropriate in atypical cases. Genetic testing distinguishes benign stationary OPN1SW tritan CVD from progressive cone dystrophies that present with early tritan defects (e.g., the 16q12/IRXB duplication disorder).

Imaging: Fundus examination and OCT are normal in congenital tritan CVD — a key discriminator from acquired tritan defects and cone dystrophies.

Differential diagnosis: - Acquired tritan defects (glaucoma, primary angle closure, diabetic retinopathy, macular telangiectasia type II, multiple sclerosis, HIV retinopathy, aging) — these have an underlying ocular/systemic cause and often additional findings. - Autosomal dominant cone dystrophy with early tritanopia (16q12/IRXB duplication) — progressive, with acuity loss. - Enhanced S-cone syndrome, blue cone monochromacy, achromatopsia — distinguished by ERG, acuity, and genetics.

Screening: No population newborn or carrier screening program exists; detection is opportunistic via color-vision testing (e.g., occupational/educational screening).

11. Outcome / Prognosis

Survival/mortality: Not affected. Congenital tritan CVD does not influence life expectancy or mortality (Finding F006).
Morbidity/function: Minimal; visual acuity and ocular health are preserved. The main impact is on color-dependent tasks and occupational suitability; congenital tritan is generally milder than red-green CVD.
Quality of life: Color vision deficiency broadly affects daily activities, education, career choice, and emotional well-being (Finding F005), but tritan-specific QoL burden is modest and many cases are undiagnosed.
Disease course / complications: None — stationary and non-degenerative; no ocular complications.
Prognostic factors/biomarkers: Not applicable; the condition is stable regardless of genotype (although genotype determines baseline severity, e.g., T190I vs classic alleles).

Overall prognosis is excellent (benign, lifelong, stable).

12. Treatment

There is no approved disease-modifying therapy for congenital tritan CVD (Finding F006). Management is:

Supportive/rehabilitative: Patient education, occupational counseling (relevant where color discrimination is safety-critical), and color-filter/assistive aids (e.g., tinted lenses, digital color-identification tools). NCIT: supportive care, visual rehabilitation.
Genetic counseling: For autosomal dominant inheritance (50% transmission risk; incomplete penetrance and variable expressivity should be conveyed).
Pharmacotherapy / surgery / immunotherapy: None applicable.
Experimental/advanced therapeutics (future): AAV-mediated cone-opsin gene augmentation has achieved robust rescue of cone structure and function in related disorders (blue cone monochromacy mouse models, e.g., C203R/C198R all-cone models), demonstrating that opsin cDNA delivery can restore cone function (Finding F006). Combined with the finding that S-opsin-null cones remain viable for ≥1.5 years (Finding F004), this makes S-cones a theoretically rescuable target. However, no tritan-specific clinical trials exist, and given the benign stationary nature of the disease, the clinical imperative for gene therapy is low compared with blinding cone disorders.

Pharmacogenomics / personalized medicine: Not applicable currently; any future approach would be genotype-guided (OPN1SW cDNA augmentation).

13. Prevention

Primary prevention: Not applicable — a germline genetic trait cannot be prevented. Preconception/prenatal genetic counseling can inform reproductive decisions.
Secondary prevention: Early detection via color-vision screening (educational/occupational) allows appropriate guidance, but there is no treatment to initiate.
Tertiary prevention: Supportive measures (assistive aids, occupational accommodation) to minimize functional impact.
Genetic screening/counseling: Cascade genetic testing within families and genetic counseling for the autosomal dominant pattern are the main preventive tools. Carrier/newborn screening programs are not established for this benign condition.
Immunization/public health/environmental interventions: Not applicable.

14. Other Species / Natural Disease

Taxonomy / orthologous gene: The mouse ortholog is Opn1sw (NCBI Gene; Mus musculus, NCBI:txid10090). S-opsin orthologs exist broadly across vertebrates; cone opsin expression is conserved and transcriptionally regulated by THRB (TRβ2), RXRγ, RORβ, RORα, and CRX (Finding F004).
Natural disease in other species: No well-characterized naturally occurring OPN1SW tritan-equivalent disease is cataloged as a major veterinary entity; S-opsin biology is primarily studied in engineered mouse models rather than spontaneous animal disease (Information limited for OMIA natural-disease entries).
Comparative biology: Mouse S-opsin-null cones survive long-term and show compensatory M-opsin upregulation (Finding F004), illustrating conserved cone-survival mechanisms and translational competition between opsins. S-opsin also contributes to violet-light-dependent refractive development in mice (Opn1sw^−/− mice are more myopic and lack the violet-light hyperopic shift) — a species-specific role not directly part of the human color-vision phenotype.
Zoonotic potential: Not applicable (non-infectious genetic trait).

15. Model Organisms

Principal model: the Opn1sw^Neo/Neo (S-opsin knockout) mouse (Finding F004).

Feature	Detail
Model type	Mammalian genetic knockout (mouse, Mus musculus)
Construct	Neomycin cassette inserted between exons 3–4 of Opn1sw
Phenotype recapitulation	Loss of S-cone (S-opsin) function; stationary, non-degenerative — models the key human feature that S-cone defect does not kill cones
Key findings	Cones remain viable ≥1.5 years (vs rod death by 2.5 months in Rho^−/−); many ventral cones fail to form outer segments; functional cones phototransduce normally and show increased M-opsin (compensatory, via relief of translational competition)
Limitations	Mice are dichromats with a dorsal-ventral opsin gradient, lack a human-like fovea and trichromatic color vision; models S-opsin loss (haploinsufficiency-like) better than dominant missense misfolding
Related models	Opn1sw^−/− (refractive/violet-light studies); all-cone BCM gene-therapy models (C203R/C198R) used to demonstrate cone-opsin AAV rescue
Databases	MGI, IMPC, IMSR

Mouse studies underpin two central conclusions: (1) S-cones survive without their opsin (stationary phenotype, broad therapeutic window), and (2) cone-opsin cDNA delivery restores cone function (proof-of-concept for gene augmentation).

Mechanistic Model / Interpretation

    OPN1SW mutation (autosomal dominant, 7q32.1)
          │
  ┌───────────────┴────────────────┐
   Missense (L56P, G79R,              Splice-site
   S214P, P264S, R283Q, T190I)        variant
  │                                │
   S-opsin misfolding /            Haploinsufficiency
   loss of function                (reduced S-opsin quantity)
  │                                │
  └───────────────┬────────────────┘
          ▼
 Reduced / absent functional S-cone photopigment
          ▼
 Diminished S-cone phototransduction signal
          ▼
     Impaired blue-yellow (S-cone-opponent) chromatic channel
          ▼
   Selective tritan-axis color discrimination loss
   (acuity, red-green, fundus all NORMAL)
          ▼
   STATIONARY / BENIGN  ← S-cones remain viable (no degeneration)
          │
      T190I: severity modulated by retinal illuminance
      (mild tritanomaly at high Td → tritanopia at low Td)

Upstream vs downstream: The initiating lesion is the OPN1SW mutation (upstream); the most downstream event is the perceptual blue-yellow discrimination deficit. The critical "brake" on the chain is that S-cone survival is independent of S-opsin — so the disease never progresses to cell death, unlike rod opsin loss. Cell type: S-cone photoreceptor (CL:0000573). Process: phototransduction (GO:0007602) / visual perception (GO:0007601). Anatomy: retina (UBERON:0000966), photoreceptor outer segment (GO:0001750). Chemical: 11-cis-retinal chromophore (CHEBI:16066).

Evidence Base

PMID	Title (abbrev.)	Supports
23022137	Substitution of isoleucine for threonine at position 190 of S-opsin…	OPN1SW causal gene; five classic missense alleles; T190I illuminance-dependent phenotype (F001, F002)
32400513	Tritan CVD may be associated with an OPN1SW splicing defect and haploinsufficiency	Splicing/haploinsufficiency mechanism (F002)
42346125	Cone Opsins and Inherited Retinal Disease	Tritan CVD is a cone-opsin gene disorder (F001)
40769301	Global Prevalence of Congenital Color Vision Deficiency, 1932–2022	Global CVD prevalence 2.59%; tritan rarest subtype (F003)
41317340	Digital Color Vision Testing… in Multiple Sclerosis	Tritan most common acquired defect (39.9%) (F003)
21219924	A mouse M-opsin monochromat: increased M-opsin when S-opsin knocked out	Opn1sw KO cones viable ≥1.5 yr; compensatory M-opsin (F004, F006)
30443703	The impacts of abnormal color vision on people's life	QoL/occupational impact of CVD (F005)
15094734	Blue cone monochromatism: phenotype/genotype…	Supports Mollon-Reffin minimal color-discrimination testing (F005)
38060327	Structural and functional rescue of cones… C203R	Cone-opsin AAV augmentation restores cone function (F006)
25605338	Congenital Achromatopsia… PDE6C	OPN1SW G79R tritan allele co-segregating; modifier-like effect
33891002	Duplication on 16q12 (IRXB)… AD cone dystrophy with early tritanopia	Differential diagnosis: distinct progressive tritan disorder

Verbatim supporting quotes: - F001/F002: "Five mutations in the S-cone-opsin gene (OPN1SW) that give rise to different single amino-acid substitutions (L56P, G79R, S214P, P264S, R283Q) are known to be associated with tritan color-vision deficiency." and "Individuals with the T190I S-opsin mutation behaved as mild tritans at 12.3-92.3Td, but as tritanopes at 1.2-9.2Td…" (PMID:23022137) - F002: "Here we present evidence implicating disrupted RNA splicing as a potential cause of inherited tritan color vision." (PMID:32400513) - F003: "The global prevalence of CVD was estimated at 2.59%" (PMID:40769301); "tritan deficiencies being the most common pure type (39.9%)" (PMID:41317340) - F004: "cones of the Opn1sw(Neo/Neo) mouse remain viable for at least 1.5 yrs, even though many ventral cones do not form outer segments" (PMID:21219924) - F006: "gene augmentation targeting cones specifically yielded robust rescue of cone function and structure" (PMID:38060327)

Limitations and Knowledge Gaps

Small molecular evidence base. The pathogenic OPN1SW missense alleles derive from a limited number of families; functional/structural proof of misfolding for each specific allele is inferred rather than individually demonstrated.
Imprecise epidemiology. Congenital tritan prevalence is poorly quantified because the condition is benign and under-ascertained; most CVD prevalence data are dominated by red-green defects.
Penetrance/expressivity not quantified. Incomplete penetrance and variable expressivity are recognized but lack precise estimates; only T190I has a characterized illuminance-dependence.
No allele frequency data. gnomAD-level frequencies for the tritan alleles are not well established.
Model limitations. The mouse is dichromatic and fovealess; it models S-opsin loss (haploinsufficiency-like) more directly than dominant missense misfolding, and cannot reproduce human blue-yellow percepts.
No tritan-specific therapy data. Gene-therapy evidence is extrapolated from blue cone monochromacy models, not from tritan CVD itself.
Differential-diagnosis overlap. Acquired tritan defects and progressive tritanopic cone dystrophies (e.g., 16q12/IRXB) phenocopy early findings; genotype + fundus/ERG are needed to separate them.

Proposed Follow-up Experiments / Actions

Functional characterization of each OPN1SW allele (heterologous expression, spectral tuning, folding/trafficking assays, AlphaFold-guided structural modeling) to convert "inferred misfolding" into demonstrated mechanism and refine ACMG classification.
Population genomics: query gnomAD/large biobanks for OPN1SW tritan alleles to estimate true allele frequencies, penetrance, and any founder effects.
Deep phenotyping cohort using standardized tritan-vector quantification (CAD/CCT) plus S-cone ERG and AO imaging to map genotype–severity relationships and test illuminance-dependence beyond T190I.
Knock-in mouse models carrying human missense alleles (e.g., P264S, T190I) to distinguish misfolding/dominant-negative from haploinsufficiency mechanisms in vivo.
Proof-of-concept S-opsin gene augmentation in an Opn1sw-deficient model (building on BCM AAV success and demonstrated long-term S-cone viability) to establish whether S-cone function is restorable — primarily of mechanistic interest given the benign clinical course.
Natural-history / QoL study specifically in congenital tritan individuals to quantify (currently assumed modest) functional and occupational impact separately from red-green CVD.

Evidence source types represented: human clinical/psychophysical and pedigree studies (OPN1SW variants, prevalence, QoL); model-organism (Opn1sw knockout mouse, BCM gene-therapy models); computational/structural (inferred GPCR misfolding). Information explicitly flagged as "not available / not applicable" where the literature does not support a claim for this specific disease.

Artifacts

Reference Validation

Checked with linkml-reference-validator 0.3.0.

Outcome	Count
References checked	11
Resolved	11
Unresolved (possible confabulation)	0
Unverifiable	0
References weighed for topical relevance	11
On topic	9
Off topic	0

All extracted references resolved successfully.

Term Validation

Checked with linkml-term-validator 0.4.5, through the ols: adapter.

Outcome	Count
Terms checked	14
Resolved	13
Unresolved (possible confabulation)	0
Obsolete	0
Unverifiable	1
Terms whose name was checked	11
Terms named correctly	5
Terms named as a different term	1
Terms whose name is worth a second look	5

Terms the report names something else

These identifiers resolve, so nothing about them looks wrong, and the ontology calls them something unrelated to what the report calls them. That usually means the identifier is not the one the sentence needs:

MONDO:0008610 (3 mentions) - the report calls it "MONDO"; MONDO calls it blue color blindness

Terms whose name is worth a second look

The report's name for these is recognisably related to the term's own name without being one of them. A loose paraphrase reads the same way as a citation of the wrong sibling term - and so does a related synonym, which the ontology records precisely because it names something adjacent rather than the same thing - so these are listed rather than judged:

HP:0000496 (3 mentions) - the report calls it "Abnormality of color vision"; HP calls it Abnormality of eye movement
GO:0050908 (2 mentions) - the report calls it "detection of light stimulus in visual perception"; GO calls it detection of light stimulus involved in visual perception
GO:0001750 (3 mentions) - the report calls it "photoreceptor outer segment", "Subcellular level: The photoreceptor outer segment"; GO calls it photoreceptor outer segment
UBERON:0003902 (1 mention) - the report calls it "Neural retina", "Tissue/cell level: Neural retina"; UBERON calls it retinal neural layer, and lists "neural retina" among its other names
UBERON:0001782 (1 mention) - the report calls it "retinal photoreceptor layer"; UBERON calls it pigmented layer of retina, and lists "retinal pigment layer" among its other names

Terms named inconsistently

The report gives these identifiers more than one name of its own:

GO:0001750 - called "photoreceptor outer segment", "Subcellular level: The photoreceptor outer segment"
UBERON:0003902 - called "Neural retina", "Tissue/cell level: Neural retina"

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Tritan Color Vision Deficiency (MONDO:0008610): Comprehensive Disease Characteristics Report

Summary

1. Disease Information

2. Etiology

3. Phenotypes

4. Genetic / Molecular Information

5. Environmental Information

6. Mechanism / Pathophysiology

Ordered causal chain

Mechanistic detail by category

7. Anatomical Structures Affected

8. Temporal Development

9. Inheritance and Population

10. Diagnostics

11. Outcome / Prognosis

12. Treatment

13. Prevention

14. Other Species / Natural Disease

15. Model Organisms

Mechanistic Model / Interpretation

Evidence Base

Limitations and Knowledge Gaps

Proposed Follow-up Experiments / Actions

Artifacts

Reference Validation

Term Validation

Terms the report names something else

Terms whose name is worth a second look

Terms named inconsistently