CLCA1: Calcium-Activated Chloride Channel Regulator 1
A key regulator of chloride transport, mucus production, and epithelial homeostasis, implicated in asthma, cystic fibrosis, and colorectal cancer.
Gene Information Card
| Symbol | CLCA1 |
|---|---|
| Full Name | Calcium-Activated Chloride Channel Regulator 1 |
| Gene Type | Protein-coding |
| Chromosomal Location | 1p22.3 |
| NCBI Gene ID | 1179 ncbi.nlm.nih.gov/gene/1179 |
| Ensembl ID | ENSG00000116478 |
| UniProt ID | A8K7I4 |
| OMIM ID | 603906 |
| HGNC ID | 2016 |
| Aliases | CACC, CACC1, CLCA, CLCRG1, hCLCA1, CaCC-1 |
Description
CLCA1 (Calcium-Activated Chloride Channel Regulator 1) is a member of the calcium-sensitive chloride conductance protein family. It is primarily expressed in epithelial cells of the respiratory and gastrointestinal tracts, where it regulates chloride ion transport, mucus secretion, and cell adhesion. CLCA1 is involved in the pathogenesis of inflammatory airway diseases, cystic fibrosis, and certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Asthma | CLCA1 upregulation enhances mucus production and airway hyperresponsiveness via calcium-activated chloride channel activity. | PMID: 15128703; ClinVar |
| Cystic Fibrosis | CLCA1 modulates CFTR-dependent chloride secretion and mucus viscosity, contributing to airway obstruction. | PMID: 19213879; NCBI Gene |
| Colorectal Cancer | CLCA1 expression is frequently downregulated in colorectal tumors; loss correlates with poor prognosis and metastasis. | PMID: 15282350; COSMIC |
| Chronic Obstructive Pulmonary Disease (COPD) | Increased CLCA1 expression in airway epithelium promotes mucus hypersecretion and inflammation. | PMID: 19850963; NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Colon | 35.2 | High |
| Lung | 18.7 | Medium |
| Trachea | 22.1 | Medium |
| Small Intestine | 15.4 | Medium |
| Stomach | 8.9 | Low |
| Esophagus | 6.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Caco-2 (Colorectal) | 42.5 | High expression; used in transport studies |
| HT-29 (Colorectal) | 38.1 | High expression; mucus-secreting line |
| A549 (Lung) | 12.3 | Moderate expression; airway epithelial model |
| HBE (Bronchial Epithelial) | 9.8 | Moderate expression; primary-like cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.128G>A (p.Arg43Gln) | Missense | <0.01% | Unknown functional effect; rare population variant |
| c.487C>T (p.Arg163Trp) | Missense | <0.01% | Reported in colorectal cancer; potential loss of function |
| c.1024_1025insA (p.Thr342Asnfs*2) | Frameshift | <0.01% | Predicted loss of function; observed in lung adenocarcinoma |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations (e.g., p.Thr342Asnfs*2) are predicted to truncate the protein, impairing chloride channel regulation and mucus homeostasis.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in CLCA1.
Dominant Negative (DN)
No evidence of dominant-negative effects for CLCA1 mutations.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Calcium signaling pathway (KEGG: hsa04020)
• Chloride channel activity (Reactome: R-HSA-983712)
• Epithelial cell signaling in Helicobacter pylori infection (KEGG: hsa05120)
Protein Summary
The CLCA1 protein is a 914-amino acid transmembrane glycoprotein localized to the apical plasma membrane of epithelial cells. It functions as a regulator of calcium-activated chloride channels (CaCCs), modulating chloride ion conductance and fluid secretion. CLCA1 also mediates cell-cell adhesion via its von Willebrand factor type A (vWA) domain and is involved in mucus production through interaction with mucins. Proteolytic cleavage generates N-terminal and C-terminal fragments that may have distinct roles. Altered expression or function of CLCA1 contributes to airway hypersecretion in asthma and COPD, impaired chloride transport in cystic fibrosis, and tumor suppression in colorectal cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CLCA1 Knockout HEK293 Cell Line | EDJ-KQ4285 | Human | 1179 | Details Get a Quote |
| CLCA1 Knockout HeLa Cell Line | EDJ-KQ52923 | Human | 1179 | Details Get a Quote |
| CLCA1 Knockout A-549 Cell Line | EDJ-KQ61390 | Human | 1179 | Details Get a Quote |
| CLCA1 Knockout HCT 116 Cell Line | EDJ-KQ69885 | Human | 1179 | Details Get a Quote |
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