POC1A

protein-coding

POC1 centriolar protein A, 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. Mutations in this gene result in short stature, onychodysplasia, facial dysmorphism, and hypotrichosis (SOFT) syndrome. [provided by RefSeq, Sep 2012]

Previous symbols:

WDR51A

MANE transcript

NM_015426.5

Inheritance

ClinVar variants

P:30U:97B:71

Top phenotype

Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis (SOFT syndrome)

gnomAD constraint

pLI —, LoF o/e 0.57

Max pathogenic AF

—

Genomic locus

chr3:52,075,226-52,154,690

External References & Databases

Ensembl (ENSG00000164087)

Transcript & Mutation Effects

hg38 • Region Span ~79.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013894

Submitter: G2P

short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013894

Submitter: Labcorp Genetics (formerly Invitae)

short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013894

Submitter: Orphanet

short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013894

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis (SOFT syndrome)AR

Manifestation: Craniofacial; Dental; Dermatologic; Endocrine; Genitourinary; Musculoskeletal; Neurologic

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: 22840363; 22840364; 22440536

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to POC1A variants in ClinVar

9 Conditions Cataloged

not providedTotal: 166

Inborn genetic diseasesTotal: 60

Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndromeTotal: 33

not specifiedTotal: 22

POC1A-related disorderTotal: 10

POC1A-related syndromeTotal: 2

Ateleiotic dwarfismTotal: 1

MicrocephalyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015426.5. 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			2 clinvar	58 clinvar	1 clinvar	61
missense	3 clinvar	2 clinvar	93 clinvar	10 clinvar	2 clinvar	110
nonsense	1 clinvar	3 clinvar				4
start loss	1 clinvar	1 clinvar				2
frameshift	9 clinvar	2 clinvar	1 clinvar			12
splice donor/acceptor (+/-2bp)	1 clinvar	7 clinvar	1 clinvar			9
Total	15	15	97	68	3	198

Highest pathogenic variant AF is 0.000019827698

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 68 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015426.5	RefSeq	NP_056241.3	11	MANE Select
ENST00000296484.7	Ensembl	ENSP00000296484.2	11	MANE Select
NM_001161580.2	RefSeq	NP_001155052.1	10	Standard
NM_001161581.2	RefSeq	NP_001155053.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

growth plate cartilage chondrocyte development
mitotic spindle organization
spermatogenesis
positive regulation of centrosome duplication
non-motile 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: ENST00000296484
Coding exons: 11
Length: 79438
Individuals with no LoFs: 125721
Homozygous LoFs: 0
Heterozygous LoFs: 27
Defined: 125748
p: 0.000107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.08	201	249	0.808	0.0000149	2654
Missense (PolyPhen)		79	102.02	0.77437		1031
Synonymous	0.673	93	102	0.915	0.00000660	810
Loss of Function	1.80	12	20.9	0.575	0.00000106	228

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00011	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0.00020	0.00020	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays an important role in centriole assembly and/or stability and ciliogenesis. Involved in early steps of centriole duplication, as well as in the later steps of centriole length control. Acts in concert with POC1B to ensure centriole integrity and proper mitotic spindle formation. {ECO:0000269|PubMed:19109428, ECO:0000269|PubMed:23015594}.;
Disease: DISEASE: Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis (SOFT) [MIM:614813]: A syndrome characterized by severely short long bones, peculiar facies associated with paucity of hair, and nail anomalies. Growth retardation is evident on prenatal ultrasound as early as the second trimester of pregnancy, and affected individuals reach a final stature consistent with a height age of 6 years to 8 years. Relative macrocephaly is present during early childhood but head circumference is markedly low by adulthood. Psychomotor development is normal. Facial dysmorphism includes a long, triangular face with prominent nose and small ears, and affected individuals have an unusual high-pitched voice. Clinodactyly, brachydactyly, and hypoplastic distal phalanges and fingernails are present in association with postpubertal sparse and short hair. Typical skeletal findings include short and thick long bones with mild irregular metaphyseal changes, short femoral necks, and hypoplastic pelvis and sacrum. All long bones of the hand are short, with major delay of carpal ossification and cone- shaped epiphyses. Vertebral body ossification is also delayed. {ECO:0000269|PubMed:22840363, ECO:0000269|PubMed:22840364}. Note=The disease is caused by mutations affecting the gene represented in this entry. Cells derived from affected individuals have abnormal mitotic mechanics with multipolar spindles, in addition to clearly impaired ciliogenesis.;

Recessive Scores

pRec: 0.108

Intolerance Scores

RVIS EVS: 0.46
RVIS percentile EVS: 78.59

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): H
Indispensability pred.: N
Indispensability score: 0.283

Gene Damage Prediction

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