CCDC3
Chr 10coiled-coil domain containing 3
The CCDC3 protein negatively regulates TNF-induced inflammatory responses in endothelial cells by inhibiting NF-kappaB activation and positively regulates lipid accumulation in adipose cells. Currently, no established human diseases have been definitively linked to CCDC3 mutations in the medical literature. The gene shows low constraint to loss-of-function variation (pLI = 0.005, LOEUF = 1.09), suggesting it may tolerate heterozygous loss-of-function variants.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
101 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 20 | 0 | 20 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 56 | 8 | 0 | 64 |
Likely Benign | 0 | 3 | 1 | 0 | 4 |
Benign | 1 | 0 | 1 | 0 | 2 |
| Total | 1 | 59 | 31 | 0 | 91 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CCDC3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools