🔗

Mappings

MONDO

MONDO:0012477 retinitis pigmentosa 33 Not Yet Curated

👪

Inheritance

1

Autosomal dominant inheritance HP:0000006

Heterozygous variants with variable onset and severity and occasional non-penetrance.

Autosomal dominant inheritance

Show evidence (2 references)

PMID:19878916 SUPPORT Human clinical

"The c.3260C>T substitution showed complete cosegregation with the retinitis pigmentosa (RP) phenotype over four generations, but was absent in a panel of 400 controls."

Dominant segregation over four generations in the founding family.

PMID:24319334 SUPPORT Human clinical

"Clinical examination of patients with SNRNP200 mutations showed a wide range of clinical symptoms and severity, including one instance of non-penetrance."

Variable expressivity and non-penetrance.

?

Discussions and Knowledge Gaps

1

Does mutant Brr2 cause disease by sitting in spliceosomes as a weak helicase, or by actively interfering with the wild-type protein?

OPEN QUESTION OPEN snrnp200_altered_function_or_dominant_negative

Attached to

pathophysiology#Impaired Brr2 U4/U6 Unwinding

The RP mutants assemble into spliceosomes like wild type yet unwind U4/U6 poorly and fail at 5' splice-site recognition, which fits a partly active helicase competing for spliceosome slots. In zebrafish the mutant human protein, but not the wild-type one, injures the retina on a normal background, which suggests a toxic or dominant-negative effect. No study has titrated mutant against wild-type Brr2 in human retinal cells, which is what would decide whether lowering the mutant allele could help.

Show evidence (1 reference)

PMID:33553197 SUPPORT Model organism

"Overexpression of SNRNP200Arg2030Cys, but not SNRNP200WT caused systemic deformities in the wild-type zebrafish embryos with the retina primarily injured"

Evidence for a harmful effect of the mutant protein itself.

⚙

Pathophysiology

4

SNRNP200 Missense Variant in the Brr2 Helicase Cassette

Heterozygous missense variants concentrate in exons 16 and 25. The recurrent p.Ser1087Leu and p.Arg1090Leu lie in the ratchet helix of the first Sec63 domain, which governs directional unwinding.

SNRNP200 hgnc:30859

RNA helicase activity GO:0003724

U4/U6.U5 tri-snRNP GO:0046540

Downstream

Impaired Brr2 U4/U6 Unwinding

Show evidence (2 references)

PMID:19878916 SUPPORT Human clinical

"The p.S1087L mutation and p.R1090L, another adRP-associated allele, reside in the "ratchet" helix of the first of two Sec63 domains implicated in the directionality and processivity of nucleic acid unwinding."

Locates the recurrent variants in the helicase ratchet helix.

PMID:24319334 SUPPORT Human clinical

"Pathogenic mutations were found primarily in exons 16 and 25"

Variant clustering in a US cohort.

Impaired Brr2 U4/U6 Unwinding

RP variants weaken Brr2 RNA binding, ATPase and helicase activity and alter how Brr2 contacts U4 and U6 in the spliceosome, so U4/U6 is unwound inefficiently at activation. The mutant protein still assembles into snRNPs and spliceosomes, so this is an altered-function defect within the machine rather than a shortage of it.

U4/U6 release during spliceosome activation GO:0000388 ↓ DECREASED

Brr2 RNA helicase activity GO:0003724 ↓ DECREASED

Downstream

Defective 5' Splice-Site Recognition with Cryptic Site Use

Show evidence (4 references)

PMID:27072132 SUPPORT In vitro / ex vivo

"The Δ247-Brr2 RP mutants exhibit a gradient of severity of weakened RNA binding, reduced helicase activity, and reduced ATPase activity compared with wild type Δ247-Brr2."

Purified Brr2 RP mutants are deficient helicases.

PMID:40045025 SUPPORT In vitro / ex vivo

"The significantly broader binding profile of mutated SNRNP200 within the U4 region upstream of the U4/U6 stem I strongly suggests that its activity to unwind snRNAs is impaired."

iCLIP in HeLa and RPE cells shows altered U4 binding by mutant SNRNP200.

PMID:19878916 SUPPORT Model organism

"marked defects in U4/U6 unwinding, but not U4/U6-U5 snRNP assembly, were observed in budding yeast for the analogous mutations (N1104L and R1107L) of the corresponding Brr2p residues"

Yeast equivalents unwind poorly but assemble normally.

+ 1 more reference

Defective 5' Splice-Site Recognition with Cryptic Site Use

In human cells, losing wild-type Brr2 increases use of a cryptic 5' splice site at the expense of the correct one, and the RP mutants cannot restore correct site choice, so the variants impair Brr2's role in 5' splice-site recognition. Which retinal transcripts are affected has not been mapped.

mRNA 5'-splice site recognition GO:0000395 ⚠ ABNORMAL

Downstream

Photoreceptor Dysfunction and Degeneration

Show evidence (2 references)

PMID:24302620 SUPPORT In vitro / ex vivo

"Proper splicing of optimal and cryptic splice sites was restored in cells expressing BRR2-wt but not in cells expressing RP mutants."

RP mutants fail to restore correct splice-site choice.

PMID:24302620 SUPPORT In vitro / ex vivo

"Taken together, our data suggest that BRR2 is an important factor in 5'-splice-site recognition and that the RP-linked mutations c.3260C>T (p.S1087L) and c.3269G>T (p.R1090L) affect this BRR2 function."

Places the defect at 5' splice-site recognition.

Photoreceptor Dysfunction and Degeneration

Rods fail first and cones later. In Drosophila carrying human RP substitutions in Snrnp200, photoreceptors are mispatterned and electrophysiologically abnormal, with mitochondrial defects and altered redox-gene expression; in zebrafish, the mutant but not the wild-type human protein injures the retina.

rod photoreceptor CL:0000604 cone photoreceptor CL:0000573

Animal models

Drosophila Snrnp200 RP knock-in Fruit fly partially recapitulates Reproduces photoreceptor patterning and electrophysiology defects from the human substitutions in the conserved orthologue.

Downstream

Night blindness

Rod-cone dystrophy

Abnormal electroretinogram

Show evidence (3 references)

PMID:42593897 SUPPORT Model organism

"When human RP-causing mutations were modeled in Drosophila Snrnp200, they resulted in abnormal retinal electrophysiology and defective patterning of photoreceptors."

Photoreceptor defects from RP substitutions in the fly orthologue.

PMID:42593897 SUPPORT Model organism

"Further analysis of the photoreceptors revealed mitochondrial defects and altered expression of genes related to redox homeostasis."

Mitochondrial and redox changes in mutant photoreceptors.

PMID:33553197 SUPPORT Model organism

"Overexpression of SNRNP200Arg2030Cys, but not SNRNP200WT caused systemic deformities in the wild-type zebrafish embryos with the retina primarily injured"

The mutant protein is harmful on a wild-type background, consistent with an altered-function or dominant-negative effect.

⬡

Pathograph

Use Group by to collapse related nodes into one box. Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.

●

Phenotypes

5

Night blindness VERY_FREQUENT Ophthalmological HP:0000662

Show evidence (2 references)

PMID:31486839 SUPPORT Human clinical

"each presented with nyctalopia, typically in the first 2 decades of life, although 2 patients experienced symptom onset in middle age"

Nyctalopia in all nine patients, usually early.

PMID:31260034 SUPPORT Human clinical

"Nyctalopia and photophobia were reported by 6/6 and 2/6 patients, respectively."

Nyctalopia in all six patients.

Rod-cone dystrophy VERY_FREQUENT Ophthalmological HP:0000510

Show evidence (1 reference)

PMID:31486839 SUPPORT Human clinical

"Retinal imaging studies and electroretinography findings were typical of a rod-predominant dystrophy with later involvement of cone photoreceptors."

Rod-cone pattern on imaging and ERG.

Abnormal electroretinogram Ophthalmological HP:0000512

Show evidence (1 reference)

PMID:31486839 SUPPORT Human clinical

"Retinal imaging studies and electroretinography findings were typical of a rod-predominant dystrophy with later involvement of cone photoreceptors."

ERG abnormality in nine SNRNP200 patients.

Reduced visual acuity Ophthalmological HP:0007663

Show evidence (1 reference)

PMID:31260034 SUPPORT Human clinical

"disease severity (visual acuity of 20/20-20/200 in the seventh to eighth decade)"

Acuity ranges from normal to 20/200 late in life with the dominant variant.

Spicular pigmentation of the retina Ophthalmological HP:0007737

Show evidence (1 reference)

PMID:19878916 SUPPORT Human clinical

"Consistently, bone-spicule-like pigmentary deposits were observed in the local peripheral retina of both eyes during funduscopy (Figure 2D)."

Bone-spicule pigment in an affected member of the founding family.

🧬

Genetic Associations

1

SNRNP200 (Causative heterozygous missense variants, mostly in the first helicase cassette.)

Gene: SNRNP200 hgnc:30859 relationship_type: CAUSATIVE variant_origin: GERMLINE

Show evidence (3 references)

PMID:19878916 SUPPORT Human clinical

"Here, we report the identification of a missense mutation, c.3260C>T (p.S1087L), in exon 25 of the SNRNP200 gene in an RP33-linked family."

Founding gene-disease report.

PMID:19710410 SUPPORT Human clinical

"Sequencing of ASCC3L1 in an affected family member showed a heterozygous single-base-pair change; c.3269G-->T, predicted to result in an Arg1090Leu amino acid change."

Independent family with the second recurrent variant, under the former gene symbol ASCC3L1.

CGGV:assertion_41acb15c-18a0-412b-a308-66a7f4e2837a-2022-05-24T160000.000Z SUPPORT Other

ClinGen Definitive classification for this disease.

💊

Medical Actions

1

Genetic Counseling

Action: Genetic Counseling NCIT:C15240

Counseling for a dominant disorder with variable onset and occasional non-penetrance.

🐁

Animal Models

1

Drosophila Snrnp200 RP knock-in

Species

Fruit fly

Genotype

Human RP substitutions introduced into Drosophila Snrnp200

Publication

PMID:42593897

Pathograph links

Photoreceptor Dysfunction and Degeneration partially recapitulates fidelity: low observes: cellular Reproduces photoreceptor patterning and electrophysiology defects from the human substitutions in the conserved orthologue.

Limitations: The fly compound eye differs from the vertebrate retina, with no rod-cone distinction and no retinal pigment epithelium, so the rod-first course of the human disease cannot be tested.

Show evidence (1 reference)

PMID:42593897 SUPPORT Model organism

"When human RP-causing mutations were modeled in Drosophila Snrnp200, they resulted in abnormal retinal electrophysiology and defective patterning of photoreceptors."

The model's photoreceptor phenotype.

{ }

Source YAML

click to show

name: SNRNP200-Related Dominant Retinopathy
creation_date: "2026-10-25T00:00:00Z"
category: Mendelian
description: >-
  SNRNP200-related dominant retinopathy (retinitis pigmentosa 33, RP33) is an
  autosomal dominant rod-cone degeneration caused by heterozygous missense
  variants in SNRNP200, which encodes Brr2, the U5 snRNP RNA helicase that
  unwinds the U4/U6 snRNA duplex to activate the spliceosome. Recurrent
  variants such as p.Ser1087Leu and p.Arg1090Leu sit in the ratchet helix of
  the first helicase cassette. The mutant helicase still assembles into
  spliceosomes but unwinds U4/U6 poorly, and its loss of function at 5'
  splice-site recognition lets cryptic sites be used. Patients present with
  night blindness, usually in the first two decades, and a rod-predominant
  dystrophy that later involves cones. Onset and severity vary widely and
  penetrance is incomplete. SNRNP200 accounts for about 1.6 percent of
  autosomal dominant retinitis pigmentosa, and its course is milder on
  average than PRPF-gene retinopathy.
disease_term:
  preferred_term: SNRNP200-related dominant retinopathy
  term:
    id: MONDO:0800098
    label: SNRNP200-related dominant retinopathy
synonyms:
- Retinitis pigmentosa 33
- RP33
- SNRNP200 retinitis pigmentosa
- BRR2-associated retinitis pigmentosa
parents:
- Ophthalmological Disease
- Retinal Dystrophy
- Inherited retinal dystrophy
- Spliceosomopathy
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0012477
      label: retinitis pigmentosa 33
    mapping_predicate: skos:narrowMatch
    mapping_source: MONDO
    notes: >-
      Retinitis pigmentosa 33 is the classically named clinical entity and the
      only MONDO child of the SNRNP200 gene-series term used as this entry's
      disease_term.
inheritance:
- name: Autosomal dominant inheritance
  inheritance_term:
    preferred_term: Autosomal dominant inheritance
    term:
      id: HP:0000006
      label: Autosomal dominant inheritance
  description: >-
    Heterozygous variants with variable onset and severity and occasional
    non-penetrance.
  evidence:
  - reference: PMID:19878916
    reference_title: "Autosomal-dominant retinitis pigmentosa caused by a mutation in SNRNP200, a gene required for unwinding of U4/U6 snRNAs."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The c.3260C>T substitution showed complete cosegregation with the retinitis pigmentosa (RP) phenotype over four generations, but was absent in a panel of 400 controls."
    explanation: Dominant segregation over four generations in the founding family.
  - reference: PMID:24319334
    reference_title: "Mutations in the small nuclear riboprotein 200 kDa gene (SNRNP200) cause 1.6% of autosomal dominant retinitis pigmentosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Clinical examination of patients with SNRNP200 mutations showed a wide range of clinical symptoms and severity, including one instance of non-penetrance."
    explanation: Variable expressivity and non-penetrance.
pathophysiology:
- name: SNRNP200 Missense Variant in the Brr2 Helicase Cassette
  conforms_to: "spliceosome_component_dysfunction#Germline Spliceosome Component Variant"
  description: >-
    Heterozygous missense variants concentrate in exons 16 and 25. The
    recurrent p.Ser1087Leu and p.Arg1090Leu lie in the ratchet helix of the
    first Sec63 domain, which governs directional unwinding.
  biological_scale: MOLECULAR
  genes:
  - preferred_term: SNRNP200
    term:
      id: hgnc:30859
      label: SNRNP200
  molecular_functions:
  - preferred_term: RNA helicase activity
    term:
      id: GO:0003724
      label: RNA helicase activity
  cellular_components:
  - preferred_term: U4/U6.U5 tri-snRNP
    term:
      id: GO:0046540
      label: U4/U6 x U5 tri-snRNP complex
  evidence:
  - reference: PMID:19878916
    reference_title: "Autosomal-dominant retinitis pigmentosa caused by a mutation in SNRNP200, a gene required for unwinding of U4/U6 snRNAs."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The p.S1087L mutation and p.R1090L, another adRP-associated allele, reside in the \"ratchet\" helix of the first of two Sec63 domains implicated in the directionality and processivity of nucleic acid unwinding."
    explanation: Locates the recurrent variants in the helicase ratchet helix.
  - reference: PMID:24319334
    reference_title: "Mutations in the small nuclear riboprotein 200 kDa gene (SNRNP200) cause 1.6% of autosomal dominant retinitis pigmentosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Pathogenic mutations were found primarily in exons 16 and 25"
    explanation: Variant clustering in a US cohort.
  downstream:
  - target: Impaired Brr2 U4/U6 Unwinding
    causal_link_type: DIRECT
- name: Impaired Brr2 U4/U6 Unwinding
  description: >-
    RP variants weaken Brr2 RNA binding, ATPase and helicase activity and alter
    how Brr2 contacts U4 and U6 in the spliceosome, so U4/U6 is unwound
    inefficiently at activation. The mutant protein still assembles into snRNPs
    and spliceosomes, so this is an altered-function defect within the
    machine rather than a shortage of it.
  biological_scale: MOLECULAR
  molecular_functions:
  - preferred_term: Brr2 RNA helicase activity
    term:
      id: GO:0003724
      label: RNA helicase activity
    modifier: DECREASED
  biological_processes:
  - preferred_term: U4/U6 release during spliceosome activation
    term:
      id: GO:0000388
      label: spliceosome conformational change to release U4 (or U4atac) and U1 (or U11)
    modifier: DECREASED
  evidence:
  - reference: PMID:27072132
    reference_title: "Retinitis Pigmentosa Mutations in Bad Response to Refrigeration 2 (Brr2) Impair ATPase and Helicase Activity."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "The Δ247-Brr2 RP mutants exhibit a gradient of severity of weakened RNA binding, reduced helicase activity, and reduced ATPase activity compared with wild type Δ247-Brr2."
    explanation: Purified Brr2 RP mutants are deficient helicases.
  - reference: PMID:40045025
    reference_title: "Retinitis pigmentosa-linked mutations impair the snRNA unwinding activity of SNRNP200 and reduce pre-mRNA binding of PRPF8."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "The significantly broader binding profile of mutated SNRNP200 within the U4 region upstream of the U4/U6 stem I strongly suggests that its activity to unwind snRNAs is impaired."
    explanation: iCLIP in HeLa and RPE cells shows altered U4 binding by mutant SNRNP200.
  - reference: PMID:19878916
    reference_title: "Autosomal-dominant retinitis pigmentosa caused by a mutation in SNRNP200, a gene required for unwinding of U4/U6 snRNAs."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "marked defects in U4/U6 unwinding, but not U4/U6-U5 snRNP assembly, were observed in budding yeast for the analogous mutations (N1104L and R1107L) of the corresponding Brr2p residues"
    explanation: Yeast equivalents unwind poorly but assemble normally.
  - reference: PMID:24302620
    reference_title: "Retinitis pigmentosa mutations of SNRNP200 enhance cryptic splice-site recognition."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "Mutations in BRR2 did not compromise snRNP assembly and both mutants were incorporated into the spliceosome just as the wild-type (wt) protein."
    explanation: Mutant Brr2 is incorporated normally in human cells.
  downstream:
  - target: Defective 5' Splice-Site Recognition with Cryptic Site Use
    causal_link_type: DIRECT
- name: Defective 5' Splice-Site Recognition with Cryptic Site Use
  conforms_to: "spliceosome_component_dysfunction#Mis-Splicing of a Sensitive Transcript Subset"
  description: >-
    In human cells, losing wild-type Brr2 increases use of a cryptic 5' splice
    site at the expense of the correct one, and the RP mutants cannot restore
    correct site choice, so the variants impair Brr2's role in 5' splice-site
    recognition. Which retinal transcripts are affected has not been mapped.
  biological_scale: CELLULAR
  biological_processes:
  - preferred_term: mRNA 5'-splice site recognition
    term:
      id: GO:0000395
      label: mRNA 5'-splice site recognition
    modifier: ABNORMAL
  evidence:
  - reference: PMID:24302620
    reference_title: "Retinitis pigmentosa mutations of SNRNP200 enhance cryptic splice-site recognition."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "Proper splicing of optimal and cryptic splice sites was restored in cells expressing BRR2-wt but not in cells expressing RP mutants."
    explanation: RP mutants fail to restore correct splice-site choice.
  - reference: PMID:24302620
    reference_title: "Retinitis pigmentosa mutations of SNRNP200 enhance cryptic splice-site recognition."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "Taken together, our data suggest that BRR2 is an important factor in 5'-splice-site recognition and that the RP-linked mutations c.3260C>T (p.S1087L) and c.3269G>T (p.R1090L) affect this BRR2 function."
    explanation: Places the defect at 5' splice-site recognition.
  downstream:
  - target: Photoreceptor Dysfunction and Degeneration
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
- name: Photoreceptor Dysfunction and Degeneration
  conforms_to: "spliceosome_component_dysfunction#Failure of Splicing-Sensitive Cell Populations"
  description: >-
    Rods fail first and cones later. In Drosophila carrying human RP
    substitutions in Snrnp200, photoreceptors are mispatterned and
    electrophysiologically abnormal, with mitochondrial defects and altered
    redox-gene expression; in zebrafish, the mutant but not the wild-type
    human protein injures the retina.
  biological_scale: CELLULAR
  cell_types:
  - preferred_term: rod photoreceptor
    term:
      id: CL:0000604
      label: retinal rod cell
  - preferred_term: cone photoreceptor
    term:
      id: CL:0000573
      label: retinal cone cell
  evidence:
  - reference: PMID:42593897
    reference_title: "N-acetylcysteine suppresses retinal defects in Drosophila models of SNRNP200-associated retinitis pigmentosa."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "When human RP-causing mutations were modeled in Drosophila Snrnp200, they resulted in abnormal retinal electrophysiology and defective patterning of photoreceptors."
    explanation: Photoreceptor defects from RP substitutions in the fly orthologue.
  - reference: PMID:42593897
    reference_title: "N-acetylcysteine suppresses retinal defects in Drosophila models of SNRNP200-associated retinitis pigmentosa."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Further analysis of the photoreceptors revealed mitochondrial defects and altered expression of genes related to redox homeostasis."
    explanation: Mitochondrial and redox changes in mutant photoreceptors.
  - reference: PMID:33553197
    reference_title: "SNRNP200 Mutations Cause Autosomal Dominant Retinitis Pigmentosa."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Overexpression of SNRNP200Arg2030Cys, but not SNRNP200WT caused systemic deformities in the wild-type zebrafish embryos with the retina primarily injured"
    explanation: >-
      The mutant protein is harmful on a wild-type background, consistent with
      an altered-function or dominant-negative effect.
  downstream:
  - target: Night blindness
  - target: Rod-cone dystrophy
  - target: Abnormal electroretinogram
phenotypes:
- name: Night blindness
  category: Ophthalmological
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Night blindness
    term:
      id: HP:0000662
      label: Nyctalopia
  evidence:
  - reference: PMID:31486839
    reference_title: "Clinical Characterization of Retinitis Pigmentosa Associated With Variants in SNRNP200."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "each presented with nyctalopia, typically in the first 2 decades of life, although 2 patients experienced symptom onset in middle age"
    explanation: Nyctalopia in all nine patients, usually early.
  - reference: PMID:31260034
    reference_title: "Genotype-Phenotype Analysis of a Novel Recessive and a Recurrent Dominant SNRNP200 Variant Causing Retinitis Pigmentosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Nyctalopia and photophobia were reported by 6/6 and 2/6 patients, respectively."
    explanation: Nyctalopia in all six patients.
- name: Rod-cone dystrophy
  category: Ophthalmological
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Rod-predominant dystrophy
    term:
      id: HP:0000510
      label: Rod-cone dystrophy
  evidence:
  - reference: PMID:31486839
    reference_title: "Clinical Characterization of Retinitis Pigmentosa Associated With Variants in SNRNP200."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Retinal imaging studies and electroretinography findings were typical of a rod-predominant dystrophy with later involvement of cone photoreceptors."
    explanation: Rod-cone pattern on imaging and ERG.
- name: Abnormal electroretinogram
  category: Ophthalmological
  phenotype_term:
    preferred_term: Diminished electroretinogram
    term:
      id: HP:0000512
      label: Abnormal electroretinogram
  evidence:
  - reference: PMID:31486839
    reference_title: "Clinical Characterization of Retinitis Pigmentosa Associated With Variants in SNRNP200."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Retinal imaging studies and electroretinography findings were typical of a rod-predominant dystrophy with later involvement of cone photoreceptors."
    explanation: ERG abnormality in nine SNRNP200 patients.
- name: Reduced visual acuity
  category: Ophthalmological
  phenotype_term:
    preferred_term: Reduced visual acuity
    term:
      id: HP:0007663
      label: Reduced visual acuity
  evidence:
  - reference: PMID:31260034
    reference_title: "Genotype-Phenotype Analysis of a Novel Recessive and a Recurrent Dominant SNRNP200 Variant Causing Retinitis Pigmentosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "disease severity (visual acuity of 20/20-20/200 in the seventh to eighth decade)"
    explanation: Acuity ranges from normal to 20/200 late in life with the dominant variant.
- name: Spicular pigmentation of the retina
  category: Ophthalmological
  phenotype_term:
    preferred_term: Bone spicule pigmentation
    term:
      id: HP:0007737
      label: Spicular pigmentation of the retina
  evidence:
  - reference: PMID:19878916
    reference_title: "Autosomal-dominant retinitis pigmentosa caused by a mutation in SNRNP200, a gene required for unwinding of U4/U6 snRNAs."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Consistently, bone-spicule-like pigmentary deposits were observed in the local peripheral retina of both eyes during funduscopy (Figure 2D)."
    explanation: Bone-spicule pigment in an affected member of the founding family.
genetic:
- name: SNRNP200
  gene_term:
    preferred_term: SNRNP200
    term:
      id: hgnc:30859
      label: SNRNP200
  association: >-
    Causative heterozygous missense variants, mostly in the first helicase
    cassette.
  relationship_type: CAUSATIVE
  variant_origin: GERMLINE
  case_fractions:
  - population: A well-characterized cohort of 251 autosomal dominant retinitis pigmentosa families
    case_fraction_percent: 1.6
    cohort_size: 251
    evidence:
    - reference: PMID:24319334
      reference_title: "Mutations in the small nuclear riboprotein 200 kDa gene (SNRNP200) cause 1.6% of autosomal dominant retinitis pigmentosa."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Mutations in SNRNP200 caused 1.6% of disease in our adRP cohort."
      explanation: >-
        SNRNP200 share of adRP in the 251-family cohort; the 21 additional
        eyeGENE families tested in the same study are not part of this
        figure.
  gene_disease_validity:
  - validity_classification: DEFINITIVE
    classified_by: CLINGEN
    external_id: CGGV:assertion_41acb15c-18a0-412b-a308-66a7f4e2837a-2022-05-24T160000.000Z
    evidence:
    - reference: CGGV:assertion_41acb15c-18a0-412b-a308-66a7f4e2837a-2022-05-24T160000.000Z
      reference_title: "SNRNP200 / SNRNP200-related dominant retinopathy (Definitive)"
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "SNRNP200 | HGNC:30859 | SNRNP200-related dominant retinopathy | MONDO:0800098 | AD | Definitive"
      explanation: ClinGen gene-disease validity record classifying this pair as Definitive.
  evidence:
  - reference: PMID:19878916
    reference_title: "Autosomal-dominant retinitis pigmentosa caused by a mutation in SNRNP200, a gene required for unwinding of U4/U6 snRNAs."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Here, we report the identification of a missense mutation, c.3260C>T (p.S1087L), in exon 25 of the SNRNP200 gene in an RP33-linked family."
    explanation: Founding gene-disease report.
  - reference: PMID:19710410
    reference_title: "Mutations in ASCC3L1 on 2q11.2 are associated with autosomal dominant retinitis pigmentosa in a Chinese family."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Sequencing of ASCC3L1 in an affected family member showed a heterozygous single-base-pair change; c.3269G-->T, predicted to result in an Arg1090Leu amino acid change."
    explanation: Independent family with the second recurrent variant, under the former gene symbol ASCC3L1.
  - reference: CGGV:assertion_41acb15c-18a0-412b-a308-66a7f4e2837a-2022-05-24T160000.000Z
    reference_title: "SNRNP200 / SNRNP200-related dominant retinopathy (Definitive)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "SNRNP200 | HGNC:30859 | SNRNP200-related dominant retinopathy | MONDO:0800098 | AD | Definitive"
    explanation: ClinGen Definitive classification for this disease.
animal_models:
- name: Drosophila Snrnp200 RP knock-in
  species: Fruit fly
  genotype: Human RP substitutions introduced into Drosophila Snrnp200
  publication: PMID:42593897
  modeled_mechanisms:
  - target: Photoreceptor Dysfunction and Degeneration
    relationship: PARTIALLY_RECAPITULATES
    fidelity: LOW
    model_scale: CELLULAR
    description: >-
      Reproduces photoreceptor patterning and electrophysiology defects from
      the human substitutions in the conserved orthologue.
    limitations: >-
      The fly compound eye differs from the vertebrate retina, with no rod-cone
      distinction and no retinal pigment epithelium, so the rod-first course of
      the human disease cannot be tested.
    evidence:
    - reference: PMID:42593897
      reference_title: "N-acetylcysteine suppresses retinal defects in Drosophila models of SNRNP200-associated retinitis pigmentosa."
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: "When human RP-causing mutations were modeled in Drosophila Snrnp200, they resulted in abnormal retinal electrophysiology and defective patterning of photoreceptors."
      explanation: The model's photoreceptor phenotype.
treatments:
- name: Genetic Counseling
  description: >-
    Counseling for a dominant disorder with variable onset and occasional
    non-penetrance.
  treatment_term:
    preferred_term: Genetic Counseling
    term:
      id: NCIT:C15240
      label: Genetic Counseling
discussions:
- discussion_id: snrnp200_altered_function_or_dominant_negative
  kind: OPEN_QUESTION
  status: OPEN
  attaches_to:
  - pathophysiology#Impaired Brr2 U4/U6 Unwinding
  prompt: >-
    Does mutant Brr2 cause disease by sitting in spliceosomes as a weak
    helicase, or by actively interfering with the wild-type protein?
  rationale: >-
    The RP mutants assemble into spliceosomes like wild type yet unwind U4/U6
    poorly and fail at 5' splice-site recognition, which fits a partly active
    helicase competing for spliceosome slots. In zebrafish the mutant human
    protein, but not the wild-type one, injures the retina on a normal
    background, which suggests a toxic or dominant-negative effect. No study has
    titrated mutant against wild-type Brr2 in human retinal cells, which is
    what would decide whether lowering the mutant allele could help.
  evidence:
  - reference: PMID:33553197
    reference_title: "SNRNP200 Mutations Cause Autosomal Dominant Retinitis Pigmentosa."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Overexpression of SNRNP200Arg2030Cys, but not SNRNP200WT caused systemic deformities in the wild-type zebrafish embryos with the retina primarily injured"
    explanation: Evidence for a harmful effect of the mutant protein itself.
references:
- reference: PMID:19878916
  title: "Autosomal-dominant retinitis pigmentosa caused by a mutation in SNRNP200, a gene required for unwinding of U4/U6 snRNAs."
- reference: PMID:24319334
  title: "Mutations in the small nuclear riboprotein 200 kDa gene (SNRNP200) cause 1.6% of autosomal dominant retinitis pigmentosa."
notes: >-
  A homozygous SNRNP200 missense variant (p.Arg545His) causing recessive
  retinitis pigmentosa with distinct dot-like hypopigmentation is described in
  PMID:31260034; this entry covers the dominant disease only, and the
  photophobia that study reports pools the dominant family with the recessive
  patient, so it is not curated here. In an Irish cohort, variants in the PRPF
  genes caused more severe retinal degeneration than SNRNP200 variants
  (PMID:42405195). ClinGen's evidence summary lists attenuated vessels, optic
  disc pallor and macular degeneration among general retinitis pigmentosa
  features; they are not curated here without an SNRNP200 patient source. No GeneReviews
  chapter is specific to SNRNP200.

📚

References & Deep Research

References

2

PMID:19878916

Autosomal-dominant retinitis pigmentosa caused by a mutation in SNRNP200, a gene required for unwinding of U4/U6 snRNAs.

No top-level findings curated for this source.

PMID:24319334

Mutations in the small nuclear riboprotein 200 kDa gene (SNRNP200) cause 1.6% of autosomal dominant retinitis pigmentosa.

No top-level findings curated for this source.

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.

Claude Code ▸

SNRNP200-Related Dominant Retinopathy (RP33): Research Report

claude-haiku-5-5, claude-sonnet-5-5 9 citations 2026-10-25T16:37:52.163669

SNRNP200-Related Dominant Retinopathy (RP33): Research Report

Scope and verification status. I could reach PubMed search listings, a Frontiers full-text page, and web-search summaries. PubMed abstract pages returned 429 or cookie walls. A script to pull abstracts from Europe PMC needed an approval that did not come through, so I did not run it. Consequences: - PMIDs below come from a PubMed result list (title, first author, journal, year). That list shows titles only, so PMIDs are reliable but content descriptions of papers I did not open are inferred from titles. - The only verbatim quote I confirmed is one sentence from Zhang 2021 (Section 3). Everything else is paraphrase and is marked as such. - Items marked [unverified] need checking before they go into the KB. Run just fetch-reference PMID:… and copy exact snippets from the cache.

0. Identifier discrepancy to resolve first

The template gives MONDO:0800098. I could not confirm it.
Searches (MedGen, DrugMap, Monarch/MGI mirrors) returned MONDO:0012477 with OMIM:610359. These are for "retinitis pigmentosa 33" (RP33), defined as retinitis pigmentosa caused by mutation in SNRNP200. MGI OMIM:610359, LOVD RP33, MedGen
Look up both CURIEs with runoak before binding. If MONDO:0800098 is a gene-defined "SNRNP200-related" umbrella term, check the lump/split and mappings.mondo_mappings predicate (exactMatch or narrowMatch only retire the stub).
I found no Orphanet ORPHA code. Gene OMIM is 601664. OMIM 601664

1. Disease information

Overview. RP33 is nonsyndromic autosomal dominant retinitis pigmentosa (adRP). It is a rod-cone degeneration caused by heterozygous missense variants in SNRNP200 (2q11.2).
Gene function. SNRNP200 encodes BRR2 (Brr2), a DEXH-box RNA helicase in the U5 snRNP and the U4/U6-U5 tri-snRNP. It unwinds the U4/U6 duplex to activate the spliceosome. GeneCards
Discovery. Zhao et al. 2009 (Am J Hum Genet, PMID:19878916) mapped RP33 to 2cen-q12.1. They found c.3260C>T (p.S1087L), segregating through four generations and absent in 400 controls (from search summary AJHG 2009 abstract mirror). The title, from PubMed, describes a mutation affecting U4/U6 unwinding.
Synonyms. RP33; retinitis pigmentosa 33; SNRNP200-related retinitis pigmentosa; BRR2/ASCC3L1-associated adRP (the older gene name ASCC3L1 appears in Li 2010, PMID:19710410).
Data type. Aggregated disease-level resources (OMIM, MONDO, ClinVar) plus family and cohort reports.
Related spliceosomal adRP. PRPF3, PRPF4, PRPF6, PRPF8, PRPF31 and SNRNP200 form a "splicing-factor RP" group. See reviews PMID:34395430 (Yang 2021) and PMID:27302685 (Růžičková 2017), and the GeneReviews overview PMID:20301590. This group is a candidate for a Grouping entry, not for lumping.

2. Etiology

Cause. Monogenic, germline, dominant. No environmental cause is known.
Genetic risk. Pathogenic or likely pathogenic missense variants in SNRNP200. Modifier genes are not established [unverified].
Environmental, protective and gene-environment factors. None reported in my searches.
Recessive alleles. Gerth-Kahlert 2019 (PMID:31260034, title: "Recessive and dominant SNRNP200 variants causing RP") suggests some alleles act recessively. Read this paper before deciding whether the entry needs a recessive subtype.

3. Phenotypes

Clinical features. The terms below are suggested from MedGen's HPO listing for RP33 and from general adRP knowledge. Percentages, onset and severity are not extracted. Frequency data would come from PMID:31486839 (Yusuf 2019, JAMA Ophthalmol, "Clinical characterization of RP with SNRNP200 variants"), which I did not read.

Phenotype	Suggested HPO	Notes
Night blindness (nyctalopia)	HP:0000662	Early symptom; MedGen lists it
Rod-cone dystrophy / retinitis pigmentosa	HP:0000510	Core feature
Optic disc pallor	HP:0000543	MedGen lists it
Constriction of peripheral visual field	HP:0001133	Expected in adRP
Reduced or absent ERG	HP:0000550 / HP:0000512	Expected
Bone-spicule retinal pigmentation	HP:0007737	Expected
Reduced visual acuity	HP:0007663	Late

All HPO CURIEs are from memory and must be looked up before use.

Onset. In the one family I could read (Zhang 2021, PMID:33553197, Front Med), night-vision symptoms began at ages 5, 7 and 9. Children's onset is therefore possible.
Severity. Reports suggest a severe, early-onset adRP spectrum [unverified].
Quote (verified from the Frontiers page): "Heterozygous SNRNP200c.C6088T (p.Arg2030Cys) mutation was ascertained in two members of this family." Frontiers
Family detail from the same page. The variant was in the proband (27) and his father (48). A third affected relative (III-2) lacked the variant, suggesting a phenocopy or a second cause. This weakens simple segregation for p.R2030C.
Quality of life. I found no data.

4. Genetic and molecular information

Gene. SNRNP200 (HGNC symbol; KB form hgnc:30[unverified, look up]), OMIM 601664, 2q11.2.
Variants (confirmed in search summaries):
c.3260C>T, p.S1087L: the original and recurrent hotspot. See Chen 2013 (PMID:24499697), whose title names the p.S1087L hotspot.
c.3269G>T, p.R1090L: reported in a 4-generation Chinese family (Li 2010, PMID:19710410, per the OMIM summary).
p.R2030C (Zhang 2021, PMID:33553197).
Other variant papers (content inferred from titles only):
Benaglio 2011, PMID:21618346 (pooled sequencing, new SNRNP200 mutations).
Liu 2012, PMID:23029027 (novel missense in a Chinese family).
Zhang 2013, PMID:23887765 (southern Chinese cohort).
Bowne 2013, PMID:24319334, titled "SNRNP200 causes 1.6% of adRP" (a Mol Vis cohort study).
Pan 2014, PMID:24940031.
Coussa 2015, PMID:26720483 (French Canadian).
Van Cauwenbergh 2017, PMID:28076437 (Belgian).
Ezquerra-Inchausti 2017, PMID:28045043 (Spanish).
Wu 2018, PMID:30360737.
Xiao 2021, PMID:33598457 (138 Chinese adRP families).
Lee 2023, PMID:36856324.
Finnegan 2026, PMID:42405195 (Irish cohort).
Variant class. Heterozygous missense, clustered in the helicase cassettes. S1087L and R1090L sit in the "ratchet" helix of the first Sec63 domain (search summary). No truncating variants are reported in my sources.
Allele frequency and ClinVar/ClinGen classification. I did not look these up. Check ClinGen gene-disease validity with just check-gene-validity.
Functional consequence. Not simple loss of function. Evidence is for impaired U4/U6 unwinding, altered splice-site fidelity and altered RNA binding. A dominant-negative mechanism is proposed on zebrafish evidence (Zhang 2021), and the Zimmann 2025 paper is worded as a partial loss/altered function [unverified]. Use functional_impact_category carefully (e.g. DOMINANT_NEGATIVE only if a source states it).
Somatic or germline. Germline.
Epigenetics and chromosomal abnormalities. Not applicable or not reported.

5. Environmental information

Not applicable. No toxins, lifestyle factors or infectious agents are reported as contributors. Separately, SNRNP200 has a role in viral RNA sensing and IRF3 activation (Tremblay 2016, PMID:27454487). That is an immune function of the protein, not an infectious cause of the retinopathy.

6. Mechanism and pathophysiology

Causal chain (steps marked inferred are not directly demonstrated in patient retina):

A heterozygous missense variant in SNRNP200 (e.g. S1087L, R1090L) changes the Brr2 helicase. These variants sit in the first Sec63 ratchet region (search summary).
The altered Brr2 is still incorporated into the spliceosome. snRNP assembly is not compromised (human-cell study, search summary of PMID:26968627 [PMID from a DisGeNET index entry; verify]).
U4/U6 unwinding is impaired. The yeast Brr2p equivalents show marked unwinding defects without assembly defects (search summary of Zhao 2009).
The mutant protein changes binding to U4 and U6 snRNAs (iCLIP, FRAP and helicase assays in HeLa and RPE cells, PMC11883072 = Zimmann 2025, PMID:40045025). Mutant Brr2 also spends less time on pre-mRNAs (Cvačková 2014, PMID:24302620, per OMIM summary).
Splicing fidelity falls, with more cryptic 5' splice-site use in a β-globin reporter (OMIM summary of Cvačková 2014) and altered splicing of cellular transcripts such as LDHA (NLK record summary).
Inferred: the altered splicing of retina-relevant transcripts, together with spliceosome stress in cells with a very high splicing load, causes rod photoreceptor and RPE dysfunction.
Rod photoreceptors degenerate, then cones, causing night blindness, field loss and eventual central vision loss.

Open questions. Why a ubiquitous protein harms mainly the retina is unresolved. Tissue-specificity reviews are PMID:40264708 (Kemal 2025) and PMID:27302685. A Brr2–Prp8 interaction is relevant, because the Prp8 C-terminal tail inhibits Brr2 (Mozaffari-Jovin 2013, PMID:23704370), and the Zimmann 2025 title concerns SNRNP200 variants and PRPF8 binding. Mozaffari-Jovin 2014 (PMID:24643059) covers Brr2 regulation and retinal disease.

Suggested ontology terms (look up before use; GO IDs from memory): - GO: mRNA splicing, via spliceosome (GO:0000398); U4/U6 x U5 tri-snRNP complex (GO:0046540); RNA helicase activity (GO:0003724). - CL: retinal rod cell (CL:0000604); retinal pigment epithelial cell (CL:0002586); retinal cone cell (CL:0000573). - No transcriptomic, proteomic or metabolomic patient datasets were found. Zimmann 2025 contains iCLIP data from HeLa and RPE cells.

7. Anatomical structures affected

Organ. Retina, bilateral; the optic disc is secondarily pale. UBERON suggestions (verify): retina (UBERON:0000966), eye (UBERON:0000970), optic disc (UBERON:0001789).
Cells. Rod photoreceptors first, then cones; RPE is implicated.
Subcellular. Nucleus, nuclear speckles and the spliceosome (GO:0005681 spliceosomal complex).
Extra-retinal. Typically none (nonsyndromic).
Lateralization. Bilateral; symmetry is not documented in my sources.

8. Temporal development

Onset. Childhood to young adult (symptoms at 5–9 years in one family). Adult-onset families are also reported for other alleles [unverified].
Progression. Progressive rod-cone degeneration. Staging and quantification are in Yusuf 2019, PMID:31486839 (unread).
Remission. None expected.

9. Inheritance and population

Inheritance. Autosomal dominant (HP:0000006). Penetrance, expressivity and any anticipation were not verified.
Prevalence of the genetic cause. Bowne 2013 (PMID:24319334): per its title, SNRNP200 accounts for about 1.6% of adRP in that cohort.
Population distribution. Chinese cohorts report repeated findings, with S1087L a hotspot (PMID:24499697). Other cohorts are listed in Section 4. A founder effect is not established.
Overall disease prevalence and sex ratio. No data found. Parent group: adRP in total is roughly 1 in 3,500–4,000 for all RP, which I am quoting from general knowledge [unverified].

10. Diagnostics

Clinical. Fundus exam, optical coherence tomography (OCT), fundus autofluorescence, visual fields and full-field ERG (rod-cone pattern). Retinal imaging details for SNRNP200 patients are in Yusuf 2019 (unread).
Genetic. Retinal dystrophy gene panels or exome sequencing. SNRNP200 is on the Genomics England PanelApp retinal panels (PanelApp). Copy-number analysis is of marginal use (Bujakowska 2017, PMID:27735924).
Differential. Other adRP genes (RHO, PRPF31, PRPF8, PRPF3, PRPF6, PRPF4, RP1, PERIPHERIN/PRPH2, IMPDH1). The GeneReviews overview PMID:20301590 gives the standard approach.
Screening. Cascade testing of relatives. No newborn screening.

11. Outcome and prognosis

No survival effect (nonsyndromic). Expected outcome is progressive vision loss with legal blindness in many older patients. Complications likely include cataract and cystoid macular edema, as in RP generally [unverified for this gene]. Genotype-specific prognosis is the focus of Yusuf 2019.

12. Treatment

No disease-modifying therapy for SNRNP200-RP is approved.
Supportive care. Low-vision rehabilitation, orientation and mobility training, and cataract or macular edema management. Suggested NCIT terms (verify): Supportive Care (NCIT:C15747), Rehabilitation (NCIT:C15315), Genetic Counseling (NCIT:C15240).
Gene therapy. Not applicable to a dominant-negative or toxic-gain allele in the usual replacement approach. Allele-specific silencing or editing is theoretical. No SNRNP200 trial was found; I did not search ClinicalTrials.gov directly.
Experimental lead. N-acetylcysteine reduced retinal defects in Drosophila SNRNP200 models (Mayer 2026, PMID:42593897, title only). Treat as preclinical.
Pharmacogenomics. None.

13. Prevention

Genetic counselling and cascade testing; prenatal or preimplantation diagnosis is possible for a known familial variant. No primary prevention exists.

14. Other species and natural disease

No naturally occurring disease linked to SNRNP200 was found in my searches. I did not check OMIA. Orthologs exist in all model species below (NCBI Gene IDs not looked up).

15. Model organisms

Zebrafish. snrnp200 is expressed in the retinal ciliary marginal zone. Mutant R2030C mRNA gave deformities in 53% of larvae versus 9% for wild type. Co-injection with morpholino raised mortality, interpreted as dominant-negative (Zhang 2021, PMID:33553197). Caveat: the text and Figure 6 legend disagree on mortality (77% vs 34%), and this is an overexpression model, so fidelity is low. Earlier work on Snrnp200 knockdown in rods is Liu 2015, PMID:26137319.
Mouse. Graziotto 2011 (PMID:20811066) describes three splicing-factor RP mouse models (title: late-onset degeneration). Per the title these are Prpf3, Prpf8 and Prpf31 models, not Snrnp200, [unverified]. I found no Snrnp200 patient-allele mouse.
Drosophila. SNRNP200 models (Mayer 2026, PMID:42593897).
C. elegans. Splicing-related RP mutations modeled (Kukhtar 2020, PMID:31919495).
Yeast. Brr2p mutants show U4/U6 unwinding defects (see Section 6).
Human cells and iPSC. HeLa and RPE cells (Zimmann 2025). An iPSC line from an adRP patient exists (Zhang 2025, PMID:40403403, which I have not confirmed carries a SNRNP200 variant).
Dismech note. Use animal_models for zebrafish, Drosophila and C. elegans, with modeled_mechanisms links. Use experimental_models for cell lines and iPSC. Cell-line splicing data should carry evidence_source: IN_VITRO.

Curation recommendations

Verify MONDO:0800098 vs MONDO:0012477 first.
Fetch and read PMID:19878916, 31486839, 24319334, 31260034, 24302620, 40045025 before writing evidence; copy snippets from the cache, not from this report.
Consider a splicing-factor RP Grouping, and a module for spliceosome function (check just list-modules splic first).
Treat the R2030C family as weakly segregating, because of the affected non-carrier.
Record the dominant-negative claim as proposed, not established.

Sources

Zhang 2021, Frontiers in Medicine (full text)
Zimmann 2025, Cell Mol Life Sci (PMC11883072)
OMIM 601664
AJHG 2009 abstract mirror
MGI OMIM:610359
LOVD RP33
MedGen
PanelApp SNRNP200
GeneCards SNRNP200
PubMed result list for "SNRNP200 retinitis pigmentosa" (source of all PMIDs above).

Reference Validation

Checked with linkml-reference-validator 0.3.0.

Outcome	Count
References checked	36
Resolved	36
Unresolved (possible confabulation)	0
Unverifiable	0
References weighed for topical relevance	36
On topic	32
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	25
Resolved	24
Unresolved (possible confabulation)	0
Obsolete	0
Unverifiable	1
Terms whose name was checked	8
Terms named correctly	3
Terms named as a different term	0
Terms whose name is worth a second look	5

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:0000662 (1 mention) - the report calls it "Night blindness (nyctalopia)"; HP calls it Nyctalopia, and lists "Night blindness" among its other names
HP:0000510 (1 mention) - the report calls it "Rod-cone dystrophy / retinitis pigmentosa"; HP calls it Rod-cone dystrophy, and lists "Retinitis pigmentosa" among its other names
HP:0007737 (1 mention) - the report calls it "Bone-spicule retinal pigmentation"; HP calls it Spicular pigmentation of the retina, and lists "Bone corpuscle fundus pigmentation" among its other names
GO:0000398 (1 mention) - the report calls it "GO: mRNA splicing, via spliceosome"; GO calls it mRNA splicing, via spliceosome
CL:0000604 (1 mention) - the report calls it "CL: retinal rod cell"; CL calls it retinal rod cell

Prefixes with no resolver

Terms carrying these prefixes were not checked either way, because no configured ontology covers them. An unrecognised prefix may name an ontology this run could not reach as easily as one that does not exist, so nothing here is evidence of fabrication: OMIM.

24 of 25 terms resolved to a current term; the rest could not be looked up either way.

SNRNP200-Related Dominant Retinopathy

Ask OpenScientist

OpenScientist Report

Mappings

Inheritance

Discussions and Knowledge Gaps

Pathophysiology

Pathograph

Phenotypes

Genetic Associations

Medical Actions

Animal Models

Source YAML

References & Deep Research

References

Deep Research

SNRNP200-Related Dominant Retinopathy (RP33): Research Report

0. Identifier discrepancy to resolve first

1. Disease information

2. Etiology

3. Phenotypes

4. Genetic and molecular information

5. Environmental information

6. Mechanism and pathophysiology

7. Anatomical structures affected

8. Temporal development

9. Inheritance and population

10. Diagnostics

11. Outcome and prognosis

12. Treatment

13. Prevention

14. Other species and natural disease

15. Model organisms

Curation recommendations

Sources

Reference Validation

Term Validation

Terms whose name is worth a second look

Prefixes with no resolver