CLCA2

Chr 1

chloride channel accessory 2

Also known as: CACC, CACC3, CLCRG2, CaCC-3

NCBI Gene: 9635ENSG00000137975UniProt: Q9UQC9

The CLCA2 protein regulates calcium-dependent chloride transport across cell membranes and mediates cell adhesion, particularly in epithelial tissues. Mutations in this gene have been associated with neurodevelopmental disorders, though the gene shows tolerance to loss-of-function variants based on population genetics data. The protein undergoes autoproteolytic processing and plays roles in epithelial cell stratification and tumor suppression.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
3
Pubs (1 yr)
13
P/LP submissions
0%
P/LP missense
1.27
LOEUF
—
Mechanism
Clinical Summary— CLCA2
⚡
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· 145 VUS of 178 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
1.27LOEUF
pLI 0.000
Z-score 0.08
OE 0.99 (0.77–1.27)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.37Z-score
OE missense 0.95 (0.88–1.03)
469 obs / 492.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.99 (0.77–1.27)
0≤0.351.4
Missense OE0.95 (0.88–1.03)
0≤0.61.4
Synonymous OE1.17
0≤1.21.6
LoF obs/exp: 43 / 43.6Missense obs/exp: 469 / 492.3Syn Z: -1.76

ClinVar Variant Classifications

178 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic2
VUS145
Likely Benign12
Benign3
11
Pathogenic
2
Likely Pathogenic
145
VUS
12
Likely Benign
3
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
141
4
0
145
Likely Benign
0
8
2
2
12
Benign
0
0
0
3
3
Total0149195173

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

View in ClinVar →

Protein Context — Lollipop Plot

CLCA2 · 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
Genomic, biochemical and expressional properties reveal strong conservation of the CLCA2 gene in birds and mammals
Bartenschlager F et al.·PeerJ
2022
Self-Cleavage of Human Chloride Channel Accessory 2 Causes a Conformational Shift That Depends on Membrane Anchorage and Is Required for Its Regulation of Store-Operated Calcium Entry
Ramena GT et al.·Biomedicines
2023
CLCA2 suppresses the proliferation, migration and invasion of cervical cancer.
Zhang P et al.·Exp Ther Med
2021
Epigenetic Repression of Chloride Channel Accessory 2 Transcription in Cardiac Fibroblast: Implication in Cardiac Fibrosis
Shao T et al.·Front Cell Dev Biol
2021
Correction: TP63 truncating mutation causes increased cell apoptosis and premature ovarian insufficiency by enhanced transcriptional activation of CLCA2.
Fan Y et al.·J Ovarian Res
2024
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
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