CCDC81

Chr 11

coiled-coil domain containing 81

NCBI Gene: 60494ENSG00000149201UniProt: Q6ZN84

The CCDC81 protein localizes to the centrosome, ciliary basal body, and plasma membrane, functioning in cellular structures critical for cell division and cilia formation. Mutations cause autosomal recessive short-rib thoracic dysplasia, a severe skeletal ciliopathy affecting bone and cartilage development. The gene shows tolerance to loss-of-function variants (low constraint), consistent with the recessive inheritance pattern observed in affected patients.

ResearchSummary from RefSeq
DNmechanismLOEUF 1.22
Clinical Summary— CCDC81
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
20 unique Pathogenic / Likely Pathogenic· 106 VUS of 146 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
1.22LOEUF
pLI 0.000
Z-score 0.44
OE 0.92 (0.71–1.22)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.43Z-score
OE missense 0.94 (0.85–1.03)
327 obs / 349.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.92 (0.71–1.22)
0≤0.351.4
Missense OE0.94 (0.85–1.03)
0≤0.61.4
Synonymous OE0.82
0≤1.21.6
LoF obs/exp: 36 / 39.0Missense obs/exp: 327 / 349.4Syn Z: 1.61
DN
0.6840th %ile
GOF
0.6249th %ile
LOF
0.3453th %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

146 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic1
VUS106
Likely Benign7
19
Pathogenic
1
Likely Pathogenic
106
VUS
7
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
19
0
19
Likely Pathogenic
0
0
1
0
1
VUS
0
97
9
0
106
Likely Benign
0
6
0
1
7
Benign
0
0
0
0
0
Total0103291133

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

View in ClinVar →

Protein Context — Lollipop Plot

CCDC81 · 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
Centrosome Protein CCDC81 Promotes Ciliogenesis.
Liu X et al.·Cytoskeleton (Hoboken)
2025
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