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Inheritance

1

Autosomal recessive inheritance HP:0000007

Biallelic POC1B variants, homozygous in consanguineous families and compound heterozygous elsewhere. Reported alleles include missense, in-frame deletion, nonsense, frameshift, canonical, non-canonical and deep-intronic splice variants.

Autosomal recessive inheritance

Show evidence (2 references)

PMID:25018096 SUPPORT Human Clinical

"in three siblings with autosomal-recessive cone dystrophy or cone-rod dystrophy and compound-heterozygous POC1B mutations"

Homozygous and compound heterozygous POC1B variants in two families with autosomal recessive cone or cone-rod dystrophy.

PMID:24945461 SUPPORT Human Clinical

"The disease gene mapped to a less than 2-megabase recessive locus at 12q21.33 with a logarithm of odds score of 3.92. At the locus, we identified a homozygous missense POC1B p.R106P mutation"

Independent linkage to a recessive locus in a consanguineous family, with a homozygous POC1B variant at the locus.

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Pathophysiology

4

Biallelic POC1B Loss-of-Function Variants

Biallelic POC1B variants. Missense and in-frame alleles such as p.Arg106Pro and p.Gln67del lost basal-body localization in overexpressed RPE1 cells and lost the interaction with FAM161A, although p.Arg106Pro localized normally to the centrosome in a separate HEK293T assay, so the localization defect is assay-dependent; nonsense, frameshift and splice alleles, including a deep-intronic variant that activates a pseudoexon, are predicted to remove the protein.

POC1B hgnc:30836

POC1A-POC1B heterodimerization GO:0046982 ↓ DECREASED

Downstream

Photoreceptor Basal Body and Connecting Cilium Defect POC1B normally sits at the basal body adjacent to the photoreceptor connecting cilium and binds FAM161A there; the patient alleles lose both the localization and the interaction.

Sperm Centriole and Flagellum Defect A separate branch of the same lesion in the male germline, reported in one family carrying a homozygous frameshift allele.

Show evidence (5 references)

PMID:39543170 SUPPORT In Vitro

"We demonstrate the importance of an interaction network organised by POC1A-POC1B heterodimers within the centriole lumen, where the WD40 domain of POC1B localises close to the centriole wall, while the POC5-interacting WD40 of POC1A resides in the centriole lumen."

POC1B acts as one half of the POC1A-POC1B heterodimer that organises the inner-scaffold interaction network; this is the molecular activity lost when POC1B is absent or mislocalised.

PMID:39543170 SUPPORT In Vitro

"Disruption of POC1A or POC1B leads to centriole microtubule defects and deletion of both genes causes centriole disintegration."

Loss of POC1B alone is sufficient to damage centriole microtubules.

PMID:25018096 SUPPORT In Vitro

"Upon overexpression of POC1B in human TERT-immortalized retinal pigment epithelium 1 cells, the encoded wild-type protein localized to the basal body of the primary cilium, whereas this localization was lost for p.Arg106Pro and p.Gln67del variant forms of POC1B."

Patient missense and in-frame alleles lose basal-body localization.

+ 2 more references

Photoreceptor Basal Body and Connecting Cilium Defect

POC1B is a centriolar WD40-repeat protein that, together with POC1A, maintains centriole integrity. In photoreceptors it localizes to the basal body and centriole adjacent to the connecting cilium, the specialized primary cilium through which outer-segment proteins are transported. Loss of POC1B function disrupts this sensory cilium; in zebrafish knockdown the connecting cilia are shortened and reduced and the outer segments are shortened.

retinal cone cell CL:0000573 retinal rod cell CL:0000604

cilium assembly GO:0060271 ↓ DECREASED

ciliary basal body GO:0036064 photoreceptor connecting cilium GO:0032391

Animal models

Zebrafish poc1b morphant Zebrafish partially recapitulates Knockdown shortens photoreceptor sensory cilia and outer segments.

Downstream

Progressive Cone-Predominant Photoreceptor Degeneration A defective photoreceptor sensory cilium leads to shortened outer segments and photoreceptor dysfunction.

Show evidence (3 references)

PMID:25044745 SUPPORT In Vitro

"In human and mouse retina, POC1B localized to the basal body and centriole adjacent to the connecting cilium of photoreceptors and in synapses of the outer plexiform layer."

Places POC1B at the photoreceptor basal body. Graded IN_VITRO because the localization comes from immunostaining of human and mouse retinal tissue sections, which is ex vivo, not an in vivo model experiment. The same paper's attribution of a Joubert syndrome phenotype to POC1B was later withdrawn (see notes); this localization finding is independent of that claim.

PMID:23015594 SUPPORT In Vitro

"Hence, Poc1A and Poc1B play redundant, but essential, roles in generation of stable centrioles, but Poc1B may have additional independent functions during cell cycle progression."

Establishes the centriole-integrity function of POC1B that underlies the basal-body defect.

PMID:26188096 SUPPORT Model Organism

"These data suggest that poc1b is required for normal development and ciliogenesis of retinal photoreceptor sensory cilia and other cilia."

Knockdown evidence that POC1B is required for photoreceptor sensory cilium formation.

Progressive Cone-Predominant Photoreceptor Degeneration

Photoreceptor degeneration affecting cones first and most. Most patients have generalized or peripheral cone dystrophy with normal dark-adapted responses; rod responses become subnormal in some patients and a minority progress to frank cone-rod dystrophy. Structurally the outer retina shows loss of the interdigitation zone (cone outer segment tips) and a blurred ellipsoid zone, often with a normal-appearing fundus. Severity ranges from early-childhood onset to a late-onset mild form with relatively preserved cone function.

retinal cone cell CL:0000573

retina UBERON:0000966

Downstream

Cone/cone-rod dystrophy

Undetectable light-adapted electroretinogram

Photoreceptor outer segment loss on macular OCT

Reduced visual acuity

Photophobia

Dyschromatopsia

Central scotoma

Nystagmus

Show evidence (3 references)

PMID:31390656 SUPPORT Human Clinical

"Generalized or peripheral cone dystrophy with normal funduscopic appearance is the representative phenotype of POC1B-associated retinopathy in our cohort."

The cone-predominant pattern across a seven-family cohort.

PMID:33657974 SUPPORT Human Clinical

"Follow-up three years later showed progression to a cone-rod dystrophy."

Documents progression from cone dystrophy to cone-rod dystrophy.

PMID:37227616 SUPPORT Human Clinical

"We reported the case of an older patient with POC1B-associated retinopathy, demonstrating late-onset visual decrease, good visual acuity, and relatively preserved cone system function."

The mild end of the severity range.

Sperm Centriole and Flagellum Defect

In the one family reported with both cone-rod dystrophy and oligoasthenoteratozoospermia, POC1B protein was absent from sperm, and mice knocked in for the same frameshift allele showed abnormal acrosome and flagellum formation.

sperm CL:0000019

sperm flagellum assembly GO:0120316 ↓ DECREASED acrosome assembly GO:0001675 ↓ DECREASED

testis UBERON:0000473

Animal models

Poc1b c.151delG knock-in mouse Mouse recapitulates Male knock-in mice have oligoasthenoteratozoospermia with abnormal acrosome and flagellum formation.

Downstream

Male infertility

Show evidence (1 reference)

PMID:37070736 SUPPORT Model Organism

"Additionally, testicular histology and transmission electron microscopy analysis of the testes and sperm indicated that Poc1b mutation results in abnormal formation of acrosomes and flagella."

Knock-in mice carrying the patient allele show defective acrosome and flagellum formation.

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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

10

Eye 9

Cone/cone-rod dystrophy HP:0000548

Course: PROGRESSIVE

Show evidence (2 references)

PMID:24945461 SUPPORT Human Clinical

"POC1B is a novel gene for a new disease typical of CORD except that patients did not report night blindness. The clinical course was slowly progressive."

Cone-rod dystrophy with a slowly progressive course and without reported night blindness.

PMID:34065499 SUPPORT Human Clinical

"All patients displayed a similar, slowly progressive retinopathy (cone dystrophy or cone-rod dystrophy) with normal funduscopy but disrupted outer retinal layers on optical coherence tomography and variable age of onset."

Cone or cone-rod dystrophy with normal fundus in an independent series.

Undetectable light-adapted electroretinogram VERY_FREQUENT HP:0030465

Show evidence (3 references)

PMID:24945461 SUPPORT Human Clinical

"Cone response was nonrecordable in all patients, whereas rod response was nonrecordable in the eldest patient and subnormal in the others."

Non-recordable cone responses in every affected family member.

PMID:37246743 SUPPORT Human Clinical

"Full-field electroretinography demonstrated undetectable light-adapted responses and normal dark-adapted responses in all patients."

Undetectable light-adapted with preserved dark-adapted responses in two further families.

PMID:31390656 SUPPORT Human Clinical

"The full-field photopic ERGs were reduced or extinguished with normal scotopic responses."

Reduced or extinguished photopic responses across the eight patients of the seven-family cohort; the phenotype is bound to the undetectable form, which is the commonest, and some patients have reduced rather than absent responses.

Photoreceptor outer segment loss on macular OCT VERY_FREQUENT HP:0030610

Show evidence (2 references)

PMID:31390656 SUPPORT Human Clinical

"Optical coherence tomography revealed an absence of the interdigitation zone and blurred ellipsoid zone in the posterior pole, but the foveal structures were preserved in three cases."

Loss of the cone outer segment tip line on OCT.

PMID:24945461 SUPPORT Human Clinical

"In all patients, a disrupted inner segment/outer segment line and the external limiting membrane were noted as a single blurry line at the central fovea, and the cone outer segment tip line was absent."

Absent cone outer segment tip line in every patient of the original family.

Reduced visual acuity HP:0007663

Show evidence (2 references)

PMID:29220607 SUPPORT Human Clinical

"The patient was a 20-year-old Japanese man whose chief complaint was a progressive decrease in his central vision."

Progressive loss of central vision as the presenting symptom.

PMID:37246743 SUPPORT Human Clinical

"Ophthalmic examination showed decreased Snellen visual acuities (range: 20/100-20/300) and color vision bilaterally."

Reduced visual acuity in three affected men.

Photophobia HP:0000613

Show evidence (2 references)

PMID:24945461 SUPPORT Human Clinical

"The clinical phenotype was typical CORD with photophobia, decreased central vision, and dyschromatopsia."

Photophobia reported in the original family.

PMID:34065499 SUPPORT Human Clinical

"Other symptoms were decreased visual acuity and photophobia."

Photophobia in an independent series.

Dyschromatopsia HP:0007641

Show evidence (2 references)

PMID:24945461 SUPPORT Human Clinical

"The clinical phenotype was typical CORD with photophobia, decreased central vision, and dyschromatopsia."

Impaired colour vision in the original family.

PMID:39568138 SUPPORT Human Clinical

"The proband, a 63-years old male, showed severely reduced day vision, a visual acuity of counting fingers (CF), color vision deficiency, high myopia and photophobia."

Colour vision deficiency in a further family.

Central scotoma HP:0000603

Show evidence (2 references)

PMID:39568138 SUPPORT Human Clinical

"Full visual field tests showed bilateral central scotoma, while single visual field tests indicated bilateral generalized depression of the visual field."

Bilateral central scotoma on perimetry.

PMID:25018096 SUPPORT Human Clinical

"relative central scotoma, mild peripheral constriction (13 years)"

Goldmann perimetry row of the clinical table; all four patients in the gene-discovery report had a relative or absolute central scotoma.

Nystagmus HP:0000639

Onset: INFANTILE

Show evidence (3 references)

PMID:25018096 SUPPORT Human Clinical

"in another sibling and in one isolated individual, poor visual acuity and nystagmus were present from early infancy, suggesting a form of ACHM."

Nystagmus from early infancy in two of four affected individuals, which supports the infantile onset recorded here.

PMID:25018096 SUPPORT Human Clinical

"The proband (A-II:1) of family A presented with reduced visual acuity in early infancy and mild nystagmus."

Individual-level report of early-infancy nystagmus.

PMID:34065499 SUPPORT Human Clinical

"All patients showed impaired cone function leading to reduced visual acuity, color vision disturbances, photophobia or nystagmus."

Nystagmus among the cone-dysfunction symptoms in an independent series.

High myopia HP:0011003

Show evidence (2 references)

PMID:39568138 SUPPORT Human Clinical

"The proband, a 63-years old male, showed severely reduced day vision, a visual acuity of counting fingers (CF), color vision deficiency, high myopia and photophobia."

High myopia in a homozygous POC1B patient.

PMID:41293231 SUPPORT Human Clinical

"Cycloplegic refraction showed high myopia (4 diopters and 8 diopters for the right and left eyes, respectively) with mild astigmatism."

High myopia in an affected child of a second family with a homozygous POC1B frameshift.

Genitourinary 1

Male infertility HP:0003251

Show evidence (1 reference)

PMID:37070736 SUPPORT Human Clinical

"Here, whole-exome sequencing was performed to identify a homozygous frameshift variant (c.151delG) in POC1B in the two brothers who had been diagnosed with both CORD and OAT from a consanguineous family."

Two brothers with both cone-rod dystrophy and oligoasthenoteratozoospermia.

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Genetic Associations

1

POC1B (Causal biallelic variant)

Gene: POC1B hgnc:30836

Show evidence (2 references)

PMID:25018096 SUPPORT Human Clinical

"in POC1B, encoding POC1 centriolar protein B, in three siblings with autosomal-recessive cone dystrophy or cone-rod dystrophy"

Identification of POC1B as the causal gene.

PMID:40170356 SUPPORT Human Clinical

"EOSRD and PKD can fully be ascribed to this CEP290 variant, whose effect outshines the "background" non-syndromic POC1B retinopathy and co-segregates with the severe syndromic phenotype. Our novel findings in this family no longer justify POC1B as a JBTS gene."

Withdraws the earlier attribution of Joubert syndrome to POC1B and restricts the POC1B phenotype to non-syndromic retinopathy.

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Medical Actions

1

Low-vision support and photophobia management

Action: supportive care Ontology label: Supportive Care NCIT:C15747

Platform: Device

No disease-modifying treatment exists. Management is supportive: low-vision aids, tinted or filtered lenses for photophobia, and periodic ophthalmological follow-up. Genetic testing is what separates the disorder from incomplete achromatopsia, which it resembles.

Target Phenotypes: Reduced visual acuity HP:0007663 Photophobia HP:0000613

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Prevalence

1

Worldwide

Cases In Literature Ultra Rare

No population estimate exists. POC1B accounted for 7 of 548 families in the Japan Eye Genetics Consortium inherited retinal disease database, which is a diagnostic-yield figure in a referral cohort and not a population rate.

Show evidence (2 references)

PMID:31390656 SUPPORT Human Clinical

"Whole-exome sequencing with targeted analyses identified homozygous or compound heterozygous mutations of the POC1B gene in 7 of 548 families in the JEGC database."

The share of a national retinal-dystrophy cohort explained by POC1B, showing the disorder is rare.

PMID:34065499 SUPPORT Human Clinical

"Mutations in POC1B are a rare cause of inherited retinal degeneration."

States that the disorder is a rare cause of inherited retinal disease.

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Animal Models

2

Zebrafish poc1b morphant

Morpholino knockdown of poc1b produces small eyes, impaired optokinetic responses and shortened photoreceptor outer segments, partially rescued by wild-type but not patient-allele human POC1B mRNA.

Species

Zebrafish

Genotype

poc1b translation-blocking morpholino knockdown

Publication

PMID:25018096

Pathograph links

Photoreceptor Basal Body and Connecting Cilium Defect partially recapitulates fidelity: low Knockdown shortens photoreceptor sensory cilia and outer segments.

Limitations: Transient morpholino knockdown during development rather than a stable germline allele, so it models a developmental ciliary defect and not the slowly progressive adult-onset degeneration seen in patients. The morphants also have ciliopathy features (curved body axis, heart defects) that patients do not show.

Show evidence (2 references)

PMID:25018096 SUPPORT Model Organism

"These ocular phenotypes could partially be rescued by wild-type human POC1B mRNA, but not by c.199_201del and c.317C>G mutant human POC1B mRNAs."

Allele-specific rescue ties the zebrafish phenotype to the patient variants.

+ 1 more reference

Poc1b c.151delG knock-in mouse

CRISPR knock-in of the frameshift allele found in two brothers with cone-rod dystrophy and oligoasthenoteratozoospermia.

Species

Mouse

Genotype

Poc1b c.151delG homozygous knock-in

Publication

PMID:37070736

Pathograph links

Sperm Centriole and Flagellum Defect recapitulates fidelity: moderate Male knock-in mice have oligoasthenoteratozoospermia with abnormal acrosome and flagellum formation.

Limitations: The abstract reports the reproductive phenotype only; a retinal phenotype in these mice is not described there, so the model's relevance to the cone-rod dystrophy is not established from this source.

Show evidence (1 reference)

PMID:37070736 SUPPORT Model Organism

"Notably, poc1bc.151delG/c.151delG KI male mice presented with OAT phenotype."

The knock-in reproduces the human sperm phenotype.

{ }

Source YAML

click to show

name: Cone-rod dystrophy 20
creation_date: "2026-10-08T00:00:00Z"
category: Mendelian
synonyms:
- CORD20
- POC1B cone-rod dystrophy
- POC1B-associated retinopathy
- cone-rod dystrophy caused by mutation in POC1B
- cone-rod dystrophy type 20
description: >-
  Cone-rod dystrophy 20 is a rare autosomal recessive inherited retinal
  dystrophy caused by biallelic variants in POC1B, which encodes POC1
  centriolar protein B, a core centriole protein that localises to the basal
  body of the photoreceptor connecting cilium. The retinal disease is
  cone-predominant: most reported patients have a generalized or peripheral
  cone dystrophy with absent or reduced light-adapted electroretinogram
  responses and normal or near-normal rod responses, and a minority progress to
  cone-rod dystrophy. Onset is usually in childhood to early adulthood with
  reduced central vision, photophobia and impaired colour vision, but some
  patients have poor vision and nystagmus from early infancy, an
  achromatopsia-like presentation that later deteriorates. The course is
  slowly progressive. A distinctive clinical feature is that the
  fundus often looks normal, so diagnosis rests on electroretinography and on
  optical coherence tomography, which shows loss of the interdigitation zone and
  a blurred ellipsoid zone. The cone-dominated, normal-fundus presentation can
  mimic incomplete achromatopsia. One consanguineous family with a homozygous
  frameshift variant additionally had male infertility with
  oligoasthenoteratozoospermia, consistent with the role of centrioles in the
  sperm flagellum.
disease_term:
  preferred_term: cone-rod dystrophy 20
  term:
    id: MONDO:0014427
    label: cone-rod dystrophy 20
parents:
- Cone-rod dystrophy
- Inherited retinal dystrophy
- Ciliopathy
references:
- reference: PMID:25018096
  title: Disruption of the basal body protein POC1B results in autosomal-recessive cone-rod dystrophy.
- reference: PMID:24945461
  title: Novel recessive cone-rod dystrophy caused by POC1B mutation.
- reference: PMID:31390656
  title: "Phenotypical Characteristics of POC1B-Associated Retinopathy in Japanese Cohort: Cone Dystrophy With Normal Funduscopic Appearance."
- reference: PMID:34065499
  title: Clinical Characteristics of POC1B-Associated Retinopathy and Assignment of Pathogenicity to Novel Deep Intronic and Non-Canonical Splice Site Variants.
- reference: PMID:25044745
  title: Mutation of POC1B in a severe syndromic retinal ciliopathy.
- reference: PMID:40170356
  title: Severe Joubert syndrome in family with homozygous POC1B p.Arg106Pro variant is due to a co-inherited deep-intronic mutation in the neighboring CEP290 gene.
- reference: PMID:37070736
  title: Homozygous frameshift variant in POC1B causes male infertility with oligoasthenoteratozoospermia in human and mice.
- reference: PMID:39543170
  title: An interaction network of inner centriole proteins organised by POC1A-POC1B heterodimer crosslinks ensures centriolar integrity.
inheritance:
- name: Autosomal recessive inheritance
  inheritance_term:
    preferred_term: Autosomal recessive inheritance
    term:
      id: HP:0000007
      label: Autosomal recessive inheritance
  description: >-
    Biallelic POC1B variants, homozygous in consanguineous families and
    compound heterozygous elsewhere. Reported alleles include missense,
    in-frame deletion, nonsense, frameshift, canonical, non-canonical and
    deep-intronic splice variants.
  evidence:
  - reference: PMID:25018096
    reference_title: Disruption of the basal body protein POC1B results in autosomal-recessive cone-rod dystrophy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      in three siblings with autosomal-recessive cone dystrophy or cone-rod dystrophy and compound-heterozygous POC1B mutations
    explanation: >-
      Homozygous and compound heterozygous POC1B variants in two families with
      autosomal recessive cone or cone-rod dystrophy.
  - reference: PMID:24945461
    reference_title: Novel recessive cone-rod dystrophy caused by POC1B mutation.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The disease gene mapped to a less than 2-megabase recessive locus at 12q21.33 with a logarithm of odds score of 3.92. At the locus, we identified a homozygous missense POC1B p.R106P mutation
    explanation: >-
      Independent linkage to a recessive locus in a consanguineous family,
      with a homozygous POC1B variant at the locus.
prevalence:
- population: Worldwide
  measure_type: CASES_IN_LITERATURE
  prevalence_class: ULTRA_RARE
  notes: >-
    No population estimate exists. POC1B accounted for 7 of 548 families in the
    Japan Eye Genetics Consortium inherited retinal disease database, which is a
    diagnostic-yield figure in a referral cohort and not a population rate.
  evidence:
  - reference: PMID:31390656
    reference_title: "Phenotypical Characteristics of POC1B-Associated Retinopathy in Japanese Cohort: Cone Dystrophy With Normal Funduscopic Appearance."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Whole-exome sequencing with targeted analyses identified homozygous or compound heterozygous mutations of the POC1B gene in 7 of 548 families in the JEGC database.
    explanation: >-
      The share of a national retinal-dystrophy cohort explained by POC1B,
      showing the disorder is rare.
  - reference: PMID:34065499
    reference_title: Clinical Characteristics of POC1B-Associated Retinopathy and Assignment of Pathogenicity to Novel Deep Intronic and Non-Canonical Splice Site Variants.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Mutations in POC1B are a rare cause of inherited retinal degeneration.
    explanation: >-
      States that the disorder is a rare cause of inherited retinal disease.
pathophysiology:
- name: Biallelic POC1B Loss-of-Function Variants
  biological_scale: MOLECULAR
  description: >-
    Biallelic POC1B variants. Missense and in-frame alleles such as p.Arg106Pro
    and p.Gln67del lost basal-body localization in overexpressed RPE1 cells and
    lost the interaction with FAM161A, although p.Arg106Pro localized normally to
    the centrosome in a separate HEK293T assay, so the localization defect is
    assay-dependent; nonsense, frameshift and splice alleles,
    including a deep-intronic variant that activates a pseudoexon, are
    predicted to remove the protein.
  genes:
  - preferred_term: POC1B
    term:
      id: hgnc:30836
      label: POC1B
  molecular_functions:
  - preferred_term: POC1A-POC1B heterodimerization
    modifier: DECREASED
    term:
      id: GO:0046982
      label: protein heterodimerization activity
  evidence:
  - reference: PMID:39543170
    reference_title: An interaction network of inner centriole proteins organised by POC1A-POC1B heterodimer crosslinks ensures centriolar integrity.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      We demonstrate the importance of an interaction network organised by POC1A-POC1B heterodimers within the centriole lumen, where the WD40 domain of POC1B localises close to the centriole wall, while the POC5-interacting WD40 of POC1A resides in the centriole lumen.
    explanation: >-
      POC1B acts as one half of the POC1A-POC1B heterodimer that organises the
      inner-scaffold interaction network; this is the molecular activity lost
      when POC1B is absent or mislocalised.
  - reference: PMID:39543170
    reference_title: An interaction network of inner centriole proteins organised by POC1A-POC1B heterodimer crosslinks ensures centriolar integrity.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Disruption of POC1A or POC1B leads to centriole microtubule defects and deletion of both genes causes centriole disintegration.
    explanation: >-
      Loss of POC1B alone is sufficient to damage centriole microtubules.
  - reference: PMID:25018096
    reference_title: Disruption of the basal body protein POC1B results in autosomal-recessive cone-rod dystrophy.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Upon overexpression of POC1B in human TERT-immortalized retinal pigment epithelium 1 cells, the encoded wild-type protein localized to the basal body of the primary cilium, whereas this localization was lost for p.Arg106Pro and p.Gln67del variant forms of POC1B.
    explanation: >-
      Patient missense and in-frame alleles lose basal-body localization.
  - reference: PMID:25044745
    reference_title: Mutation of POC1B in a severe syndromic retinal ciliopathy.
    supports: REFUTE
    evidence_source: IN_VITRO
    snippet: >-
      In HEK293T cells transfected with a plasmid containing the p.Arg106Pro mutation, the protein localized normally at the centrosome
    explanation: >-
      Contradicts the localization part of the claim for p.Arg106Pro in a
      different cell system; the FAM161A-binding defect is not addressed here.
  - reference: PMID:34065499
    reference_title: Clinical Characteristics of POC1B-Associated Retinopathy and Assignment of Pathogenicity to Novel Deep Intronic and Non-Canonical Splice Site Variants.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Splicing analysis revealed that the non-canonical splice site variant c.561-3T>C leads to exon skipping while the novel deep intronic variant c.1033-327T>A causes pseudoexon activation.
    explanation: >-
      Splice-assay demonstration that intronic patient alleles disrupt the
      POC1B transcript.
  downstream:
  - target: Photoreceptor Basal Body and Connecting Cilium Defect
    description: >-
      POC1B normally sits at the basal body adjacent to the photoreceptor
      connecting cilium and binds FAM161A there; the patient alleles lose both
      the localization and the interaction.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:25018096
      reference_title: Disruption of the basal body protein POC1B results in autosomal-recessive cone-rod dystrophy.
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: >-
        This was confirmed in coimmunoprecipitation and colocalization assays, which both showed loss of FAM161A interaction with p.Arg106Pro and p.Gln67del variant forms of POC1B.
      explanation: >-
        Patient alleles lose the interaction with FAM161A, a ciliopathy protein
        at the base of the photoreceptor connecting cilium.
  - target: Sperm Centriole and Flagellum Defect
    description: >-
      A separate branch of the same lesion in the male germline, reported in
      one family carrying a homozygous frameshift allele.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:37070736
      reference_title: Homozygous frameshift variant in POC1B causes male infertility with oligoasthenoteratozoospermia in human and mice.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Transcript and protein analyses of biological samples from the two patients carrying the variant showed that POC1B protein is lost in sperm cells.
      explanation: >-
        The frameshift allele removes POC1B from patient sperm.
- name: Photoreceptor Basal Body and Connecting Cilium Defect
  biological_scale: CELLULAR
  description: >-
    POC1B is a centriolar WD40-repeat protein that, together with POC1A,
    maintains centriole integrity. In photoreceptors it localizes to the basal
    body and centriole adjacent to the connecting cilium, the specialized
    primary cilium through which outer-segment proteins are transported. Loss of
    POC1B function disrupts this sensory cilium; in zebrafish knockdown the
    connecting cilia are shortened and reduced and the outer segments are
    shortened.
  cellular_components:
  - preferred_term: ciliary basal body
    term:
      id: GO:0036064
      label: ciliary basal body
  - preferred_term: photoreceptor connecting cilium
    term:
      id: GO:0032391
      label: photoreceptor connecting cilium
  biological_processes:
  - preferred_term: cilium assembly
    modifier: DECREASED
    term:
      id: GO:0060271
      label: cilium assembly
  cell_types:
  - preferred_term: retinal cone cell
    term:
      id: CL:0000573
      label: retinal cone cell
  - preferred_term: retinal rod cell
    term:
      id: CL:0000604
      label: retinal rod cell
  evidence:
  - reference: PMID:25044745
    reference_title: Mutation of POC1B in a severe syndromic retinal ciliopathy.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      In human and mouse retina, POC1B localized to the basal body and centriole adjacent to the connecting cilium of photoreceptors and in synapses of the outer plexiform layer.
    explanation: >-
      Places POC1B at the photoreceptor basal body. Graded IN_VITRO because the
      localization comes from immunostaining of human and mouse retinal tissue
      sections, which is ex vivo, not an in vivo model experiment. The same paper's
      attribution of a Joubert syndrome phenotype to POC1B was later withdrawn
      (see notes); this localization finding is independent of that claim.
  - reference: PMID:23015594
    reference_title: Poc1A and Poc1B act together in human cells to ensure centriole integrity.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Hence, Poc1A and Poc1B play redundant, but essential, roles in generation of stable centrioles, but Poc1B may have additional independent functions during cell cycle progression.
    explanation: >-
      Establishes the centriole-integrity function of POC1B that underlies the
      basal-body defect.
  - reference: PMID:26188096
    reference_title: Knockdown of poc1b causes abnormal photoreceptor sensory cilium and vision impairment in zebrafish.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      These data suggest that poc1b is required for normal development and ciliogenesis of retinal photoreceptor sensory cilia and other cilia.
    explanation: >-
      Knockdown evidence that POC1B is required for photoreceptor sensory cilium
      formation.
  downstream:
  - target: Progressive Cone-Predominant Photoreceptor Degeneration
    description: >-
      A defective photoreceptor sensory cilium leads to shortened outer
      segments and photoreceptor dysfunction.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:25018096
      reference_title: Disruption of the basal body protein POC1B results in autosomal-recessive cone-rod dystrophy.
      supports: SUPPORT
      directness: INDIRECT
      evidence_source: MODEL_ORGANISM
      snippet: >-
        Morpholino-oligonucleotide-induced knockdown of poc1b translation in zebrafish resulted in a dose-dependent small-eye phenotype, impaired optokinetic responses, and decreased length of photoreceptor outer segments.
      explanation: >-
        Loss of poc1b in zebrafish shortens photoreceptor outer segments and
        impairs visual responses; indirect because it is a morpholino
        knockdown in a non-human model.
    - reference: PMID:25018096
      reference_title: Disruption of the basal body protein POC1B results in autosomal-recessive cone-rod dystrophy.
      supports: SUPPORT
      quote_role: PRIMARY_RESULT
      evidence_source: OTHER
      snippet: >-
        Altogether, this study demonstrates that POC1B mutations result in a defect of the photoreceptor sensory cilium and thus affect cone and rod photoreceptors.
      explanation: >-
        The authors' synthesis of the human genetic, cell and zebrafish data
        linking the ciliary defect to photoreceptor disease.
- name: Progressive Cone-Predominant Photoreceptor Degeneration
  biological_scale: TISSUE
  description: >-
    Photoreceptor degeneration affecting cones first and most. Most patients
    have generalized or peripheral cone dystrophy with normal dark-adapted
    responses; rod responses become subnormal in some patients and a minority
    progress to frank cone-rod dystrophy. Structurally the outer retina shows
    loss of the interdigitation zone (cone outer segment tips) and a blurred
    ellipsoid zone, often with a normal-appearing fundus. Severity ranges from
    early-childhood onset to a late-onset mild form with relatively preserved
    cone function.
  cell_types:
  - preferred_term: retinal cone cell
    term:
      id: CL:0000573
      label: retinal cone cell
  locations:
  - preferred_term: retina
    term:
      id: UBERON:0000966
      label: retina
  evidence:
  - reference: PMID:31390656
    reference_title: "Phenotypical Characteristics of POC1B-Associated Retinopathy in Japanese Cohort: Cone Dystrophy With Normal Funduscopic Appearance."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Generalized or peripheral cone dystrophy with normal funduscopic appearance is the representative phenotype of POC1B-associated retinopathy in our cohort.
    explanation: >-
      The cone-predominant pattern across a seven-family cohort.
  - reference: PMID:33657974
    reference_title: A homozygous POC1B variant causes recessive cone-rod dystrophy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Follow-up three years later showed progression to a cone-rod dystrophy.
    explanation: >-
      Documents progression from cone dystrophy to cone-rod dystrophy.
  - reference: PMID:37227616
    reference_title: A mild form of POC1B-associated retinal dystrophy with relatively preserved cone system function.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We reported the case of an older patient with POC1B-associated retinopathy, demonstrating late-onset visual decrease, good visual acuity, and relatively preserved cone system function.
    explanation: >-
      The mild end of the severity range.
  downstream:
  - target: Cone/cone-rod dystrophy
    causal_link_type: DIRECT
  - target: Undetectable light-adapted electroretinogram
    causal_link_type: DIRECT
  - target: Photoreceptor outer segment loss on macular OCT
    causal_link_type: DIRECT
  - target: Reduced visual acuity
    causal_link_type: DIRECT
  - target: Photophobia
    causal_link_type: DIRECT
  - target: Dyschromatopsia
    causal_link_type: DIRECT
  - target: Central scotoma
    causal_link_type: DIRECT
  - target: Nystagmus
    causal_link_type: DIRECT
- name: Sperm Centriole and Flagellum Defect
  biological_scale: CELLULAR
  description: >-
    In the one family reported with both cone-rod dystrophy and
    oligoasthenoteratozoospermia, POC1B protein was absent from sperm, and mice
    knocked in for the same frameshift allele showed abnormal acrosome and
    flagellum formation.
  cell_types:
  - preferred_term: sperm
    term:
      id: CL:0000019
      label: sperm
  biological_processes:
  - preferred_term: sperm flagellum assembly
    modifier: DECREASED
    term:
      id: GO:0120316
      label: sperm flagellum assembly
  - preferred_term: acrosome assembly
    modifier: DECREASED
    term:
      id: GO:0001675
      label: acrosome assembly
  locations:
  - preferred_term: testis
    term:
      id: UBERON:0000473
      label: testis
  evidence:
  - reference: PMID:37070736
    reference_title: Homozygous frameshift variant in POC1B causes male infertility with oligoasthenoteratozoospermia in human and mice.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      Additionally, testicular histology and transmission electron microscopy analysis of the testes and sperm indicated that Poc1b mutation results in abnormal formation of acrosomes and flagella.
    explanation: >-
      Knock-in mice carrying the patient allele show defective acrosome and
      flagellum formation.
  downstream:
  - target: Male infertility
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:37070736
      reference_title: Homozygous frameshift variant in POC1B causes male infertility with oligoasthenoteratozoospermia in human and mice.
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: >-
        Notably, poc1bc.151delG/c.151delG KI male mice presented with OAT phenotype.
      explanation: >-
        The patient allele reproduces oligoasthenoteratozoospermia in mice.
phenotypes:
- name: Cone/cone-rod dystrophy
  category: Ophthalmologic
  diagnostic: true
  description: >-
    Cone dystrophy or cone-rod dystrophy, usually with onset in childhood to
    early adulthood and a slowly progressive course. Night blindness was not
    reported in the original consanguineous family.
  phenotype_term:
    preferred_term: Cone/cone-rod dystrophy
    term:
      id: HP:0000548
      label: Cone/cone-rod dystrophy
    clinical_course: PROGRESSIVE
  evidence:
  - reference: PMID:24945461
    reference_title: Novel recessive cone-rod dystrophy caused by POC1B mutation.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      POC1B is a novel gene for a new disease typical of CORD except that patients did not report night blindness. The clinical course was slowly progressive.
    explanation: >-
      Cone-rod dystrophy with a slowly progressive course and without
      reported night blindness.
  - reference: PMID:34065499
    reference_title: Clinical Characteristics of POC1B-Associated Retinopathy and Assignment of Pathogenicity to Novel Deep Intronic and Non-Canonical Splice Site Variants.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      All patients displayed a similar, slowly progressive retinopathy (cone dystrophy or cone-rod dystrophy) with normal funduscopy but disrupted outer retinal layers on optical coherence tomography and variable age of onset.
    explanation: >-
      Cone or cone-rod dystrophy with normal fundus in an independent series.
- name: Undetectable light-adapted electroretinogram
  category: Ophthalmologic
  diagnostic: true
  description: >-
    Full-field photopic responses are reduced to non-recordable while scotopic
    responses are normal or subnormal, the electrophysiological signature of a
    cone-predominant dystrophy.
  phenotype_term:
    preferred_term: Undetectable light-adapted electroretinogram
    term:
      id: HP:0030465
      label: Undetectable light-adapted electroretinogram
  frequency: VERY_FREQUENT
  evidence:
  - reference: PMID:24945461
    reference_title: Novel recessive cone-rod dystrophy caused by POC1B mutation.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Cone response was nonrecordable in all patients, whereas rod response was nonrecordable in the eldest patient and subnormal in the others.
    explanation: >-
      Non-recordable cone responses in every affected family member.
  - reference: PMID:37246743
    reference_title: Phenotypic and genotypic features of POC1B-associated cone dystrophy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Full-field electroretinography demonstrated undetectable light-adapted responses and normal dark-adapted responses in all patients.
    explanation: >-
      Undetectable light-adapted with preserved dark-adapted responses in two
      further families.
  - reference: PMID:31390656
    reference_title: "Phenotypical Characteristics of POC1B-Associated Retinopathy in Japanese Cohort: Cone Dystrophy With Normal Funduscopic Appearance."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The full-field photopic ERGs were reduced or extinguished with normal scotopic responses.
    explanation: >-
      Reduced or extinguished photopic responses across the eight patients of
      the seven-family cohort; the phenotype is bound to the undetectable form,
      which is the commonest, and some patients have reduced rather than absent
      responses.
- name: Photoreceptor outer segment loss on macular OCT
  category: Ophthalmologic
  description: >-
    Optical coherence tomography shows absence of the interdigitation zone
    (cone outer segment tip line) and a blurred ellipsoid zone, often with a
    normal fundus on ophthalmoscopy.
  phenotype_term:
    preferred_term: Photoreceptor outer segment loss on macular OCT
    term:
      id: HP:0030610
      label: Photoreceptor outer segment loss on macular OCT
  frequency: VERY_FREQUENT
  evidence:
  - reference: PMID:31390656
    reference_title: "Phenotypical Characteristics of POC1B-Associated Retinopathy in Japanese Cohort: Cone Dystrophy With Normal Funduscopic Appearance."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Optical coherence tomography revealed an absence of the interdigitation zone and blurred ellipsoid zone in the posterior pole, but the foveal structures were preserved in three cases.
    explanation: >-
      Loss of the cone outer segment tip line on OCT.
  - reference: PMID:24945461
    reference_title: Novel recessive cone-rod dystrophy caused by POC1B mutation.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In all patients, a disrupted inner segment/outer segment line and the external limiting membrane were noted as a single blurry line at the central fovea, and the cone outer segment tip line was absent.
    explanation: >-
      Absent cone outer segment tip line in every patient of the original
      family.
- name: Reduced visual acuity
  category: Ophthalmologic
  description: >-
    Decreased central vision, the usual presenting complaint.
  phenotype_term:
    preferred_term: Reduced visual acuity
    term:
      id: HP:0007663
      label: Reduced visual acuity
  evidence:
  - reference: PMID:29220607
    reference_title: Case of cone dystrophy with normal fundus appearance associated with biallelic POC1B variants.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The patient was a 20-year-old Japanese man whose chief complaint was a progressive decrease in his central vision.
    explanation: >-
      Progressive loss of central vision as the presenting symptom.
  - reference: PMID:37246743
    reference_title: Phenotypic and genotypic features of POC1B-associated cone dystrophy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Ophthalmic examination showed decreased Snellen visual acuities (range: 20/100-20/300) and color vision bilaterally.
    explanation: >-
      Reduced visual acuity in three affected men.
- name: Photophobia
  category: Ophthalmologic
  phenotype_term:
    preferred_term: Photophobia
    term:
      id: HP:0000613
      label: Photophobia
  evidence:
  - reference: PMID:24945461
    reference_title: Novel recessive cone-rod dystrophy caused by POC1B mutation.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The clinical phenotype was typical CORD with photophobia, decreased central vision, and dyschromatopsia.
    explanation: >-
      Photophobia reported in the original family.
  - reference: PMID:34065499
    reference_title: Clinical Characteristics of POC1B-Associated Retinopathy and Assignment of Pathogenicity to Novel Deep Intronic and Non-Canonical Splice Site Variants.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Other symptoms were decreased visual acuity and photophobia.
    explanation: >-
      Photophobia in an independent series.
- name: Dyschromatopsia
  category: Ophthalmologic
  phenotype_term:
    preferred_term: Dyschromatopsia
    term:
      id: HP:0007641
      label: Dyschromatopsia
  evidence:
  - reference: PMID:24945461
    reference_title: Novel recessive cone-rod dystrophy caused by POC1B mutation.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The clinical phenotype was typical CORD with photophobia, decreased central vision, and dyschromatopsia.
    explanation: >-
      Impaired colour vision in the original family.
  - reference: PMID:39568138
    reference_title: A novel homozygous missense variant in POC1B causes cone dystrophy in a consanguineous Pakistani family.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The proband, a 63-years old male, showed severely reduced day vision, a visual acuity of counting fingers (CF), color vision deficiency, high myopia and photophobia.
    explanation: >-
      Colour vision deficiency in a further family.
- name: Central scotoma
  category: Ophthalmologic
  phenotype_term:
    preferred_term: Central scotoma
    term:
      id: HP:0000603
      label: Central scotoma
  evidence:
  - reference: PMID:39568138
    reference_title: A novel homozygous missense variant in POC1B causes cone dystrophy in a consanguineous Pakistani family.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Full visual field tests showed bilateral central scotoma, while single visual field tests indicated bilateral generalized depression of the visual field.
    explanation: >-
      Bilateral central scotoma on perimetry.
  - reference: PMID:25018096
    reference_title: Disruption of the basal body protein POC1B results in autosomal-recessive cone-rod dystrophy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      relative central scotoma, mild peripheral constriction (13 years)
    explanation: >-
      Goldmann perimetry row of the clinical table; all four patients in the
      gene-discovery report had a relative or absolute central scotoma.
- name: Nystagmus
  category: Ophthalmologic
  description: >-
    Nystagmus, sometimes present from early infancy together with poor visual
    acuity, giving an achromatopsia-like presentation; it was present in two of
    the four patients in the gene-discovery report.
  phenotype_term:
    preferred_term: Nystagmus
    term:
      id: HP:0000639
      label: Nystagmus
    onset:
      onset_category: INFANTILE
  evidence:
  - reference: PMID:25018096
    reference_title: Disruption of the basal body protein POC1B results in autosomal-recessive cone-rod dystrophy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      in another sibling and in one isolated individual, poor visual acuity and nystagmus were present from early infancy, suggesting a form of ACHM.
    explanation: >-
      Nystagmus from early infancy in two of four affected individuals, which
      supports the infantile onset recorded here.
  - reference: PMID:25018096
    reference_title: Disruption of the basal body protein POC1B results in autosomal-recessive cone-rod dystrophy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The proband (A-II:1) of family A presented with reduced visual acuity in early infancy and mild nystagmus.
    explanation: >-
      Individual-level report of early-infancy nystagmus.
  - reference: PMID:34065499
    reference_title: Clinical Characteristics of POC1B-Associated Retinopathy and Assignment of Pathogenicity to Novel Deep Intronic and Non-Canonical Splice Site Variants.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      All patients showed impaired cone function leading to reduced visual acuity, color vision disturbances, photophobia or nystagmus.
    explanation: >-
      Nystagmus among the cone-dysfunction symptoms in an independent series.
- name: High myopia
  category: Ophthalmologic
  description: >-
    High myopia was reported in the Pakistani proband (PMID:39568138) and in
    one affected child of a Saudi sibship (PMID:41293231), where an affected
    adult in the same report also had myopia. Myopia is common in the general
    population and no study has tested whether it is part of the POC1B
    phenotype, so it is recorded without a frequency and is not wired to a
    mechanism.
  phenotype_term:
    preferred_term: High myopia
    term:
      id: HP:0011003
      label: High myopia
  evidence:
  - reference: PMID:39568138
    reference_title: A novel homozygous missense variant in POC1B causes cone dystrophy in a consanguineous Pakistani family.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The proband, a 63-years old male, showed severely reduced day vision, a visual acuity of counting fingers (CF), color vision deficiency, high myopia and photophobia.
    explanation: >-
      High myopia in a homozygous POC1B patient.
  - reference: PMID:41293231
    reference_title: "POC1B-associated cone-rod dystrophy with bilateral optic disc swelling: A novel clinical observation."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Cycloplegic refraction showed high myopia (4 diopters and 8 diopters for the right and left eyes, respectively) with mild astigmatism.
    explanation: >-
      High myopia in an affected child of a second family with a homozygous
      POC1B frameshift.
- name: Male infertility
  category: Reproductive
  description: >-
    Oligoasthenoteratozoospermia with male infertility, reported together with
    cone-rod dystrophy in two brothers homozygous for a POC1B frameshift
    variant. Whether it accompanies other POC1B genotypes is not known.
  phenotype_term:
    preferred_term: Male infertility
    term:
      id: HP:0003251
      label: Male infertility
  evidence:
  - reference: PMID:37070736
    reference_title: Homozygous frameshift variant in POC1B causes male infertility with oligoasthenoteratozoospermia in human and mice.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Here, whole-exome sequencing was performed to identify a homozygous frameshift variant (c.151delG) in POC1B in the two brothers who had been diagnosed with both CORD and OAT from a consanguineous family.
    explanation: >-
      Two brothers with both cone-rod dystrophy and
      oligoasthenoteratozoospermia.
genetic:
- name: POC1B
  association: Causal biallelic variant
  gene_term:
    preferred_term: POC1B
    term:
      id: hgnc:30836
      label: POC1B
  notes: >-
    The recurrent p.Arg106Pro allele was also reported homozygous in a family
    with Joubert syndrome, early-onset severe retinal dystrophy and polycystic
    kidney disease, which led to POC1B being proposed as a Joubert syndrome
    gene. Long-read genome sequencing later found a homozygous deep-intronic
    CEP290 variant, 1.28 Mb away and co-inherited in cis, that fully explains
    the syndromic features, and the authors withdrew the Joubert attribution.
    The syndromic presentation is therefore not part of this disease. No ClinGen
    gene-disease validity record was found for POC1B.
  evidence:
  - reference: PMID:25018096
    reference_title: Disruption of the basal body protein POC1B results in autosomal-recessive cone-rod dystrophy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      in POC1B, encoding POC1 centriolar protein B, in three siblings with autosomal-recessive cone dystrophy or cone-rod dystrophy
    explanation: >-
      Identification of POC1B as the causal gene.
  - reference: PMID:40170356
    reference_title: Severe Joubert syndrome in family with homozygous POC1B p.Arg106Pro variant is due to a co-inherited deep-intronic mutation in the neighboring CEP290 gene.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      EOSRD and PKD can fully be ascribed to this CEP290 variant, whose effect outshines the "background" non-syndromic POC1B retinopathy and co-segregates with the severe syndromic phenotype. Our novel findings in this family no longer justify POC1B as a JBTS gene.
    explanation: >-
      Withdraws the earlier attribution of Joubert syndrome to POC1B and
      restricts the POC1B phenotype to non-syndromic retinopathy.
environmental: []
treatments:
- name: Low-vision support and photophobia management
  description: >-
    No disease-modifying treatment exists. Management is supportive: low-vision
    aids, tinted or filtered lenses for photophobia, and periodic
    ophthalmological follow-up. Genetic testing is what separates the disorder
    from incomplete achromatopsia, which it resembles.
  therapeutic_modality: DEVICE
  treatment_term:
    preferred_term: supportive care
    term:
      id: NCIT:C15747
      label: Supportive Care
  target_phenotypes:
  - preferred_term: Reduced visual acuity
    term:
      id: HP:0007663
      label: Reduced visual acuity
  - preferred_term: Photophobia
    term:
      id: HP:0000613
      label: Photophobia
animal_models:
- name: Zebrafish poc1b morphant
  species: Zebrafish
  genotype: poc1b translation-blocking morpholino knockdown
  publication: PMID:25018096
  description: >-
    Morpholino knockdown of poc1b produces small eyes, impaired optokinetic
    responses and shortened photoreceptor outer segments, partially rescued by
    wild-type but not patient-allele human POC1B mRNA.
  modeled_mechanisms:
  - target: Photoreceptor Basal Body and Connecting Cilium Defect
    relationship: PARTIALLY_RECAPITULATES
    fidelity: LOW
    description: >-
      Knockdown shortens photoreceptor sensory cilia and outer segments.
    limitations: >-
      Transient morpholino knockdown during development rather than a stable
      germline allele, so it models a developmental ciliary defect and not the
      slowly progressive adult-onset degeneration seen in patients. The
      morphants also have ciliopathy features (curved body axis, heart defects)
      that patients do not show.
    evidence:
    - reference: PMID:25018096
      reference_title: Disruption of the basal body protein POC1B results in autosomal-recessive cone-rod dystrophy.
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: >-
        These ocular phenotypes could partially be rescued by wild-type human POC1B mRNA, but not by c.199_201del and c.317C>G mutant human POC1B mRNAs.
      explanation: >-
        Allele-specific rescue ties the zebrafish phenotype to the patient
        variants.
    - reference: PMID:26188096
      reference_title: Knockdown of poc1b causes abnormal photoreceptor sensory cilium and vision impairment in zebrafish.
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: >-
        In addition, ciliopathy-associated developmental defects, such as small eyes, curved body axis, heart defects, and shortened cilia in Kupffer's vesicle, were observed as well.
      explanation: >-
        Documents the broader developmental ciliopathy features of the
        morphants, which are the main limitation of the model.
- name: Poc1b c.151delG knock-in mouse
  species: Mouse
  genotype: Poc1b c.151delG homozygous knock-in
  publication: PMID:37070736
  description: >-
    CRISPR knock-in of the frameshift allele found in two brothers with
    cone-rod dystrophy and oligoasthenoteratozoospermia.
  modeled_mechanisms:
  - target: Sperm Centriole and Flagellum Defect
    relationship: RECAPITULATES
    fidelity: MODERATE
    description: >-
      Male knock-in mice have oligoasthenoteratozoospermia with abnormal
      acrosome and flagellum formation.
    limitations: >-
      The abstract reports the reproductive phenotype only; a retinal phenotype
      in these mice is not described there, so the model's relevance to the
      cone-rod dystrophy is not established from this source.
    evidence:
    - reference: PMID:37070736
      reference_title: Homozygous frameshift variant in POC1B causes male infertility with oligoasthenoteratozoospermia in human and mice.
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: >-
        Notably, poc1bc.151delG/c.151delG KI male mice presented with OAT phenotype.
      explanation: >-
        The knock-in reproduces the human sperm phenotype.
datasets: []
notes: >-
  Two features recur in the literature and are easy to miss. First, the fundus
  is normal or nearly normal in most reported patients, and the disease has
  been initially diagnosed as incomplete achromatopsia; electroretinography and
  OCT are needed to recognise it. Second, rod function is often normal, so many
  patients are described as having cone dystrophy rather than cone-rod
  dystrophy; MONDO and OMIM name the disease cone-rod dystrophy 20 after the
  first reported families, and the entry covers the whole cone-predominant
  spectrum. Bilateral optic disc swelling with normal lumbar-puncture opening
  pressure has been reported in two siblings of one family (PMID:41293231);
  it is not recorded as a phenotype here because it rests on a single family
  and no HPO term distinguishes non-papilledema disc swelling. No GeneReviews
  chapter covers this disease.

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References & Deep Research