POC1B

protein-coding

POC1 centriolar protein B, the group of WD repeat domain containing

Gene summary

POC1 proteins contain an N-terminal WD40 domain and a C-terminal coiled coil domain and are part of centrosomes. They play an important role in basal body and cilia formation. This gene encodes one of the two POC1 proteins found in humans. Mutation in this gene result in autosomal-recessive cone-rod dystrophy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

Previous symbols:

WDR51B

MANE transcript

NM_172240.3

Inheritance

AR, AD

ClinVar variants

P:55U:213B:85

Top phenotype

Cone-rod dystrophy 20

gnomAD constraint

pLI —, LoF o/e 0.61

Max pathogenic AF

—

Genomic locus

chr12:89,419,718-89,526,047

External References & Databases

Ensembl (ENSG00000139323)

Transcript & Mutation Effects

hg38 • Region Span ~106.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cone-rod dystrophy 20DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014427

Submitter: ClinGen

POC1B was first reported in relation to autosomal recessive cone-rod dystrophy in 2014 (Roosing S et al., PMID: 25018096). 6 variants (missense, in-frame indel, splice, frameshift) that have been reported in 13 probands in 4 publications (PMIDs: 34065499, 32244552, 24945461, 25018096 ) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity is unclear. This gene-disease relationship is also supported by experimental evidence (protein interactions) (PMID: 32110738) which confirms that POC1B interacts with FAM161A, which causes retinitis pigmentosa. In summary, there is definitive evidence supporting the relationship between POC1B and autosomal recessive retinopathy. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time.This classification was approved by the ClinGen Retina GCEP on the meeting date February, 6th, 2023. (SOP Version 11).

cone-rod dystrophy 20STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014427

Submitter: Labcorp Genetics (formerly Invitae)

cone-rod dystrophySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0015993

Submitter: Orphanet

cone-rod dystrophy 20DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014427

Submitter: G2P

cone-rod dystrophy 20STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014427

Submitter: PanelApp Australia

ciliopathyMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0005308

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Cone-rod dystrophy 20AR

Manifestation: Ophthalmologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 24945461; 25018096

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to POC1B variants in ClinVar

8 Conditions Cataloged

not providedTotal: 371

not specifiedTotal: 102

Cone-rod dystrophy 20Total: 82

Inborn genetic diseasesTotal: 59

POC1B-related disorderTotal: 31

Retinal dystrophyTotal: 17

Childhood-onset schizophreniaTotal: 1

Cone-rod dystrophyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_172240.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			5 clinvar	67 clinvar	1 clinvar	73
missense	2 clinvar	2 clinvar	203 clinvar	17 clinvar		224
nonsense	7 clinvar	10 clinvar				17
start loss		1 clinvar				1
frameshift	13 clinvar	8 clinvar	1 clinvar			22
splice donor/acceptor (+/-2bp)	4 clinvar	8 clinvar	4 clinvar			16
Total	26	29	213	84	1	353

Highest pathogenic variant AF is 0.00010360375

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 55 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_172240.3	RefSeq	NP_758440.1	12	MANE Select
ENST00000313546.8	Ensembl	ENSP00000323302.3	12	MANE Select
NM_001199777.2	RefSeq	NP_001186706.1	10	Standard
NM_001425771.1	RefSeq	NP_001412700.1	12	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
poc1b	Danio rerio	Structure: retinal cone cell Quality: decreased length abnormal

Gene / Model

Organism

Observed Phenotype

poc1b

Danio rerio

Structure: retinal cone cell

Quality: decreased length

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

retina homeostasis
cell population proliferation
cilium assembly

Molecular Function

protein binding

Cellular Component

spindle pole
centrosome
centriole
ciliary basal body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000313546
Coding exons: 12
Length: 106307
Individuals with no LoFs: 125694
Homozygous LoFs: 0
Heterozygous LoFs: 54
Defined: 125748
p: 0.000215

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0928	254	250	1.02	0.0000122	3107
Missense (PolyPhen)		82	95.44	0.85918		1213
Synonymous	1.21	76	90.7	0.838	0.00000473	906
Loss of Function	1.82	16	26.0	0.614	0.00000140	326

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00080	0.00076	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00021	0.00020	rare
South Asian	0.00026	0.00023	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays an important role in centriole assembly and/or stability and ciliogenesis (PubMed:20008567). Involved in early steps of centriole duplication, as well as in the later steps of centriole length control (PubMed:19109428). Acts in concert with POC1A to ensure centriole integrity and proper mitotic spindle formation. Required for primary cilia formation, ciliary length and also cell proliferation (PubMed:23015594). Required for retinal integrity (PubMed:25044745). {ECO:0000269|PubMed:19109428, ECO:0000269|PubMed:20008567, ECO:0000269|PubMed:23015594, ECO:0000269|PubMed:25044745}.;
Disease: DISEASE: Cone-rod dystrophy 20 (CORD20) [MIM:615973]: A form of cone-rod dystrophy, an inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa, due to cone photoreceptors degenerating at a higher rate than rod photoreceptors. {ECO:0000269|PubMed:24945461, ECO:0000269|PubMed:25018096, ECO:0000269|PubMed:25044745}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.113

Intolerance Scores

RVIS EVS: -0.23
RVIS percentile EVS: 37.32

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.781

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium