CEP85

Chr 1

centrosomal protein 85

Also known as: CCDC21

NCBI Gene: 64793ENSG00000130695UniProt: Q6P2H3OMIM: 618898

The encoded protein regulates centriole duplication through direct interaction with STIL and acts as a negative regulator of NEK2 to maintain centrosome integrity during interphase. Mutations cause nephronophthisis, a ciliopathy characterized by chronic kidney disease that can progress to end-stage renal failure, with autosomal recessive inheritance. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be pathogenic.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.53
Clinical Summary— CEP85
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.
📋
ClinVar Variants
5 unique Pathogenic / Likely Pathogenic· 108 VUS of 137 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.53LOEUF
pLI 0.000
Z-score 3.94
OE 0.34 (0.22–0.53)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.22Z-score
OE missense 0.97 (0.89–1.05)
404 obs / 416.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.34 (0.22–0.53)
0≤0.351.4
Missense OE0.97 (0.89–1.05)
0≤0.61.4
Synonymous OE0.91
0≤1.21.6
LoF obs/exp: 14 / 41.3Missense obs/exp: 404 / 416.9Syn Z: 0.89
DN
0.6550th %ile
GOF
0.6052th %ile
LOF
0.3843th %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

137 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
VUS108
Likely Benign6
Benign5
5
Pathogenic
108
VUS
6
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
0
0
0
VUS
0
103
5
0
108
Likely Benign
0
6
0
0
6
Benign
0
2
1
2
5
Total0111112124

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

View in ClinVar →

Protein Context — Lollipop Plot

CEP85 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
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 1 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