CEP135

Chr 4AR

centrosomal protein 135

Also known as: CEP4, KIAA0635, MCPH8

NCBI Gene: 9662ENSG00000174799UniProt: Q66GS9

This gene encodes a centrosomal protein, which acts as a scaffolding protein during early centriole biogenesis, and is also required for centriole-centriole cohesion during interphase. Mutations in this gene are associated with autosomal recessive primary microcephaly-8. [provided by RefSeq, Jun 2012]

Primary Disease Associations & Inheritance

Microcephaly 8, primary, autosomal recessiveMIM #614673
AR
0
Active trials
50
Pathogenic / LP
414
ClinVar variants
8
Pubs (1 yr)
0.1
Missense Z
0.81
LOEUF
Clinical Summary— CEP135
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
50 Pathogenic / Likely Pathogenic· 188 VUS of 414 total submissions
📖
GeneReview available — CEP135
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.81LOEUF
pLI 0.000
Z-score 2.87
OE 0.64 (0.50–0.81)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.08Z-score
OE missense 0.99 (0.92–1.06)
565 obs / 570.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.64 (0.50–0.81)
0≤0.351.4
Missense OE0.99 (0.92–1.06)
0≤0.61.4
Synonymous OE0.93
0≤1.21.6
LoF obs/exp: 46 / 72.4Missense obs/exp: 565 / 570.4Syn Z: 0.80
DN
DN
0.7327th %ile
GOF
0.5857th %ile
LOF
0.3454th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

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.

ClinVar Variant Classifications

414 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic17
VUS188
Likely Benign155
Benign8
Conflicting13
33
Pathogenic
17
Likely Pathogenic
188
VUS
155
Likely Benign
8
Benign
13
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
15
0
18
0
33
Likely Pathogenic
13
0
4
0
17
VUS
0
176
10
2
188
Likely Benign
0
9
58
88
155
Benign
0
3
2
3
8
Conflicting
—13
Total281889293414

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

View in ClinVar →

CEP135 · protein map & ClinVar variants

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

Gene2Phenotype Curations

CEP135-related primary microcephaly and disturbed centrosomal function

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 →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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