CEP63

Chr 3AR

centrosomal protein 63

Also known as: SCKL6

NCBI Gene: 80254 ENSG00000182923 UniProt: Q96MT8 OMIM: 614724

CEP63 encodes a centrosomal protein that is required for normal spindle assembly and centriole duplication, and plays a role in DNA damage response. Mutations cause Seckel syndrome 6, characterized by primordial dwarfism and microcephaly, with autosomal recessive inheritance. The gene shows low constraint to loss-of-function variants (pLI near zero), which is consistent with the recessive inheritance pattern observed clinically.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein with six coiled-coil domains. The protein is localized to the centrosome, a non-membraneous organelle that functions as the major microtubule-organizing center in animal cells. Several alternatively spliced transcript variants have been found, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.261 OMIM phenotype

Clinical Summary— CEP63

⚡

Population Constraint (gnomAD)

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

📋

ClinVar Variants

46 unique Pathogenic / Likely Pathogenic· 254 VUS of 535 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.26LOEUF

pLI 0.000

Z-score 0.22

OE 0.96 (0.74–1.26)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.10Z-score

OE missense 1.01 (0.93–1.11)

366 obs / 360.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.96 (0.74–1.26)

0≤0.351.4

Missense OE?1.01 (0.93–1.11)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 38 / 39.5Missense obs/exp: 366 / 360.7Syn Z: 0.72

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongCEP63-related Seckel syndromeLOFAR

This gene — mechanism propensity

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

0.6550th %ile

GOF

0.5661th %ile

LOF

0.4331th %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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

535 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27

Likely Pathogenic19

VUS254

Likely Benign128

Benign69

Conflicting12

Pathogenic

Likely Pathogenic

254

VUS

128

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	26	0	1	0	27
Likely Pathogenic	18	1	0	0	19
VUS	10	234	6	4	254
Likely Benign	0	15	49	64	128
Benign	0	6	53	10	69
Conflicting	—				12
Total	54	256	109	78	509

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

View in ClinVar →

18 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap CEP63 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →