CLCA2 Gene

HGNC Family	Chloride channel accessory (CLCA)
Name	chloride channel accessory 2
Description	This gene encodes a member of the calcium-activated chloride channel regulator (CLCR) family of proteins. Members of this family regulate the transport of chloride across the plasma membrane. The encoded protein is autoproteolytically processed to generate N- and C- terminal fragments. Expression of this gene is upregulated by the tumor suppressor protein p53 in response to DNA damage. In breast cancer, expression of this gene is downregulated and the encoded protein may inhibit migration and invasion while promoting mesenchymal-to-epithelial transition in cancer cell lines. [provided by RefSeq, Sep 2016]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CLCA2 is a multifunctional protein expressed predominantly in differentiated epithelial cells where it plays a central role in maintaining epithelial integrity and suppressing tumor progression. A number of studies have demonstrated that CLCA2 is a p53‐ and p63‐inducible gene whose up‐regulation leads to growth arrest, senescence, and apoptosis, thereby acting as a bona fide tumor suppressor."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Functionally, CLCA2 enforces the epithelial phenotype by promoting cell–cell adhesion, in part through its colocalization with adhesion molecules such as integrin β4, and by modulating chloride currents that can influence intracellular pH. The maintenance of these parameters is critical for the suppression of epithelial-to-mesenchymal transition (EMT), a process that, when dysregulated, contributes to increased migration, invasion, and metastasis in several carcinomas."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "5"}, {"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, reduced expression of CLCA2 is correlated with a more mesenchymal, migratory phenotype and poorer clinical outcomes in cancers such as breast and cervical carcinoma, underscoring its importance in tumor suppression. Through its ability to suppress focal adhesion kinase (FAK) signaling and to reinforce epithelial differentiation, CLCA2 not only limits cell migration and invasion but also acts as an essential component of a p53-dependent stress response."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, the collective evidence indicates that CLCA2 functions as a guardian of epithelial homeostasis by promoting differentiation and cell adhesion while inhibiting oncogenic processes such as EMT and metastatic dissemination."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}, {"type": "fg_f", "ref": "6"}, {"type": "fg_f", "ref": "8"}, {"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "V Walia, Y Yu, D Cao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of breast epithelial marker hCLCA2 promotes epithelial-to-mesenchymal transition and indicates higher risk of metastasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2011.392"}], "href": "https://doi.org/10.1038/onc.2011.392"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21909135"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21909135"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Vijay Walia, Ming Ding, Sumit Kumar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "hCLCA2 Is a p53-Inducible Inhibitor of Breast Cancer Cell Proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-08-4101"}], "href": "https://doi.org/10.1158/0008-5472.CAN-08-4101"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19654313"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19654313"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yasushi Sasaki, Ryota Koyama, Reo Maruyama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CLCA2, a target of the p53 family, negatively regulates cancer cell migration and invasion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Biol Ther (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/cbt.22280"}], "href": "https://doi.org/10.4161/cbt.22280"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22990203"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22990203"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Grace Ramena, Yufang Yin, Yang Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CLCA2 Interactor EVA1 Is Required for Mammary Epithelial Cell Differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0147489"}], "href": "https://doi.org/10.1371/journal.pone.0147489"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26930581"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26930581"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yang Yu, Vijay Walia, Randolph C Elble "}, {"type": "b", "children": [{"type": "t", "text": "Loss of CLCA4 promotes epithelial-to-mesenchymal transition in breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0083943"}], "href": "https://doi.org/10.1371/journal.pone.0083943"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24386311"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24386311"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Che J Connon, Satoshi Kawasaki, Kenta Yamasaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The quantification of hCLCA2 and colocalisation with integrin beta4 in stratified human epithelia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Histochem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.acthis.2004.08.003"}], "href": "https://doi.org/10.1016/j.acthis.2004.08.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15707651"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15707651"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Xin Yang, Jin-Long Cao, Feng-Na Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Decreased expression of CLCA2 and the correlating with immune infiltrates in patients with cervical squamous cell carcinoma: A bioinformatics analysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Taiwan J Obstet Gynecol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.tjog.2021.03.016"}], "href": "https://doi.org/10.1016/j.tjog.2021.03.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33966732"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33966732"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Katherine Hughes, Maximilian Blanck, Sara Pensa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Stat3 modulates chloride channel accessory protein expression in normal and neoplastic mammary tissue."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cddis.2016.302"}], "href": "https://doi.org/10.1038/cddis.2016.302"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27711075"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27711075"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "L Hämäläinen, G Bart, P Takabe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The calcium-activated chloride channel-associated protein rCLCA2 is expressed throughout rat epidermis, facilitates apoptosis and is downmodulated by UVB."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Histochem Cell Biol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00418-021-01962-5"}], "href": "https://doi.org/10.1007/s00418-021-01962-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33486586"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33486586"}]}]}]}
Synonyms	CACC3, CLCRG2, CACC-3
Proteins	CLCA2_HUMAN
NCBI Gene ID	9635
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CLCA2 has 5,379 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 112 datasets.

Click the + buttons to view associations for CLCA2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CLCA2 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by CLCA2 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of CLCA2 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of CLCA2 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of CLCA2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of CLCA2 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CLCA2 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CLCA2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of CLCA2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CLCA2 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of CLCA2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CLCA2 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CLCA2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CLCA2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of CLCA2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CLCA2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CLCA2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CLCA2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CLCA2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with CLCA2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of CLCA2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CLCA2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with CLCA2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with CLCA2 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CLCA2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CLCA2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with CLCA2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with CLCA2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CLCA2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at CLCA2 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CLCA2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CLCA2 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing CLCA2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with CLCA2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with CLCA2 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of CLCA2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with CLCA2 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing CLCA2 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of CLCA2 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of CLCA2 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Kinase Perturbations	kinase perturbations changing expression of CLCA2 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.