CLCA1

Chr 1

chloride channel accessory 1

Also known as: CACC, CACC1, CLCRG1, CaCC-1, GOB5, hCLCA1, hCaCC-1

NCBI Gene: 1179ENSG00000016490UniProt: A8K7I4

This protein is a calcium-activated chloride channel that regulates mucus production and secretion by goblet cells in the intestine and respiratory tract. CLCA1 is extremely intolerant to loss-of-function variants (pLI near 1.0), but no definitive Mendelian disease associations have been established in humans to date. The gene is primarily studied in the context of respiratory conditions like asthma and cystic fibrosis, but causative mutations for pediatric neurogenetic disorders have not been reported.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
19
Pubs (1 yr)
13
P/LP submissions
0%
P/LP missense
0.72
LOEUF
DN
Mechanism· predicted
Clinical Summary— CLCA1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
13 unique Pathogenic / Likely Pathogenic· 101 VUS of 134 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
0.72LOEUF
pLI 0.000
Z-score 2.99
OE 0.50 (0.35–0.72)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.71Z-score
OE missense 0.91 (0.84–0.98)
449 obs / 493.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.50 (0.35–0.72)
0≤0.351.4
Missense OE0.91 (0.84–0.98)
0≤0.61.4
Synonymous OE1.05
0≤1.21.6
LoF obs/exp: 21 / 41.9Missense obs/exp: 449 / 493.1Syn Z: -0.55
DN
0.7034th %ile
GOF
0.5268th %ile
LOF
0.2289th %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

134 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic2
VUS101
Likely Benign11
Benign5
11
Pathogenic
2
Likely Pathogenic
101
VUS
11
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
11
0
11
Likely Pathogenic
0
0
2
0
2
VUS
0
99
2
0
101
Likely Benign
0
11
0
0
11
Benign
0
4
1
0
5
Total0114160130

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

View in ClinVar →

Protein Context — Lollipop Plot

CLCA1 · protein map & ClinVar variants

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

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 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Integrative subtyping by bile acid metabolism identifies CLCA1/UGT2A3/ZG16 as markers of immune dysfunction and poor prognosis in colorectal cancer.
Feng L et al.·Front Oncol
2025Open Access
Quantitative proteomic and glycoproteomic analysis identifies CLCA1, FBN1, and FGB as potential biomarkers for ulcerative colitis.
Wang X et al.·RSC Adv
2025Open Access
Establishment of two pathomic-based machine learning models to predict CLCA1 expression in colon adenocarcinoma.
Yao C et al.·PLoS One
2025Open AccessFunctional
Long-Term PM2.5 Exposure and Upregulation of CLCA1 Expression in Nasal Epithelium from Youth with Asthma.
Rosser FJ et al.·Ann Am Thorac Soc
2025
Clca1 deficiency exacerbates colitis susceptibility via impairment of mucus barrier integrity and gut microbiota homeostasis.
Liu Z et al.·Microbiol Res
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