POC1A

Chr 3

POC1 centriolar protein A

Also known as: PIX2, SOFT, WDR51A

NCBI Gene: 25886 ENSG00000164087 UniProt: Q8NBT0

The POC1A protein is essential for centriole assembly and stability, and plays a critical role in ciliogenesis and proper mitotic spindle formation. Biallelic mutations cause short stature, onychodysplasia, facial dysmorphism, and hypotrichosis (SOFT) syndrome, inherited in an autosomal recessive pattern. This gene is highly constrained against loss-of-function variants, reflecting its essential cellular functions.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.93

Clinical Summary— POC1A

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

31 unique Pathogenic / Likely Pathogenic· 88 VUS of 245 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.93LOEUF

pLI 0.000

Z-score 1.80

OE 0.57 (0.37–0.93)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.08Z-score

OE missense 0.81 (0.72–0.91)

201 obs / 248.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.57 (0.37–0.93)

0≤0.351.4

Missense OE?0.81 (0.72–0.91)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 12 / 20.9Missense obs/exp: 201 / 248.9Syn Z: 0.67

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongPOC1A-related short stature, onychodysplasia, facial dysmorphism, and hypotrichosis (SOFT syndrome)LOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.77top 25%

GOF

0.6345th %ile

LOF

0.3649th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

245 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18

Likely Pathogenic13

VUS88

Likely Benign95

Benign15

Conflicting9

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	12	3	3	0	18
Likely Pathogenic	9	4	0	0	13
VUS	2	84	1	1	88
Likely Benign	0	4	39	52	95
Benign	0	2	9	4	15
Conflicting	—				9
Total	23	97	52	57	238

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

9 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap POC1A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →