CLCA4
Chr 1chloride channel accessory 4
Also known as: CaCC, CaCC2
The protein encoded by CLCA4 mediates calcium-activated chloride conductance and belongs to a family of calcium-sensitive chloride conductance proteins. This gene is extremely intolerant to loss-of-function variants (pLI near 1), but mutations causing human disease have not been established. CLCA4 maps to chromosome 1p31-p22 along with other family members and shows tissue-specific expression patterns.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
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
152 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 | 11 | 0 | 11 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 117 | 3 | 0 | 120 |
Likely Benign | 1 | 11 | 0 | 3 | 15 |
Benign | 0 | 1 | 0 | 1 | 2 |
Conflicting | — | 1 | |||
| Total | 1 | 129 | 16 | 4 | 151 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CLCA4 · 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