CEP63

Chr 3AR

centrosomal protein 63

Also known as: SCKL6

NCBI Gene: 80254ENSG00000182923UniProt: Q96MT8

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]

Primary Disease Associations & Inheritance

?Seckel syndrome 6MIM #614728
AR
0
Active trials
46
Pathogenic / LP
475
ClinVar variants
2
Pubs (1 yr)
-0.1
Missense Z
1.26
LOEUF
Clinical Summary— CEP63
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
46 Pathogenic / Likely Pathogenic· 237 VUS of 475 total submissions
Some data sources returned errors (1)

pubtator: TimeoutError: The operation was aborted due to timeout

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 OE0.96 (0.74–1.26)
0≤0.351.4
Missense OE1.01 (0.93–1.11)
0≤0.61.4
Synonymous OE0.92
0≤1.21.6
LoF obs/exp: 38 / 39.5Missense obs/exp: 366 / 360.7Syn Z: 0.72
DNLOF
DN
0.6550th %ile
GOF
0.5661th %ile
LOF
0.4331th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
LOF48% of P/LP variants are LoF

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

475 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic17
VUS237
Likely Benign124
Benign62
Conflicting6
29
Pathogenic
17
Likely Pathogenic
237
VUS
124
Likely Benign
62
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
0
20
0
29
Likely Pathogenic
13
1
3
0
17
VUS
4
220
10
3
237
Likely Benign
0
14
49
61
124
Benign
0
3
51
8
62
Conflicting
—6
Total2623813372475

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

View in ClinVar →

CEP63 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

CEP63-related Seckel syndrome

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients