CLCA2 chloride channel accessory 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CLCA2provided by HGNC
Official Full Name: chloride channel accessory 2provided by HGNC
Primary source: HGNC:HGNC:2016
See related: Ensembl:ENSG00000137975 MIM:604003; AllianceGenome:HGNC:2016
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CACC; CACC3; CLCRG2; CaCC-3
Summary: 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]
Expression: Biased expression in esophagus (RPKM 67.2), skin (RPKM 43.6) and 1 other tissue See more
Orthologs: mouse all
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Genomic context

Location:: 1p22.3

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (86424171..86456553)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (86264193..86296574)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (86889854..86922236)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Transport of CLCA2 to the nucleus by extracellular vesicles controls keratinocyte survival and migration.
Title: Transport of CLCA2 to the nucleus by extracellular vesicles controls keratinocyte survival and migration.
TP63 truncating mutation causes increased cell apoptosis and premature ovarian insufficiency by enhanced transcriptional activation of CLCA2.
Title: TP63 truncating mutation causes increased cell apoptosis and premature ovarian insufficiency by enhanced transcriptional activation of CLCA2.
CLCA2 overexpression suppresses epithelial-to-mesenchymal transition in cervical cancer cells through inactivation of ERK/JNK/p38-MAPK signaling pathways.
Title: CLCA2 overexpression suppresses epithelial-to-mesenchymal transition in cervical cancer cells through inactivation of ERK/JNK/p38-MAPK signaling pathways.
Decreased expression of CLCA2 and the correlating with immune infiltrates in patients with cervical squamous cell carcinoma: A bioinformatics analysis.
Title: Decreased expression of CLCA2 and the correlating with immune infiltrates in patients with cervical squamous cell carcinoma: A bioinformatics analysis.
Genome-wide meta-analysis identified novel variant associated with hallux valgus in Caucasians.
Title: Genome-wide meta-analysis identified novel variant associated with hallux valgus in Caucasians.
CLCA2 was identified as a potential prognostic marker for triple negative breast cancer in African American women.
Title: CLCA2 expression is associated with survival among African American women with triple negative breast cancer.
CLCA2 knockdown promoted keratinocyte apoptosis induced by hyperosmotic stress through impairment of cell-cell adhesion.
Title: Humidity-regulated CLCA2 protects the epidermis from hyperosmotic stress.
A novel heterozygous missense mutation c.G1725T of the CLCA2 gene may be associated with heart block disease.
Title: A newly identified missense mutation in CLCA2 is associated with autosomal dominant cardiac conduction block.
CLCA2 suppress NPC proliferation, migration, invasion and epithelial-mesenchymal transition through inhibiting FAK/ERK signaling.
Title: Along with its favorable prognostic role, CLCA2 inhibits growth and metastasis of nasopharyngeal carcinoma cells via inhibition of FAK/ERK signaling.
identified a new molecular mechanism to explain PCa and MeS link based on CLCA2 repression by CTBP1 and miR-196b-5p molecules that might act as key factors in the progression onset of this disease
Title: CLCA2 epigenetic regulation by CTBP1, HDACs, ZEB1, EP300 and miR-196b-5p impacts prostate cancer cell adhesion and EMT in metabolic syndrome disease.

Submit: New GeneRIF Correction See all GeneRIFs (24)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 from both CCR5- and CXCR4-tropic HIV-1 strains opens calcium-activated potassium (K(Ca)), chloride, and calcium-permeant nonselective cation channels in macrophages; these signals are mediated by CCR5 and CXCR4	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH119026 (e-PCR)
- UniSTS:138255

G59429 (e-PCR)
- UniSTS:136740

G54627 (e-PCR)
- UniSTS:117828

SHGC-156130 (e-PCR)
- UniSTS:182119

SHGC-75095 (e-PCR)
- UniSTS:72101

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables chloride channel activity	TAS Traceable Author Statement more info	PubMed
enables intracellularly calcium-gated chloride channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables metalloendopeptidase activity	TAS Traceable Author Statement more info

Process	Evidence Code	Pubs
involved_in cell adhesion	IEA Inferred from Electronic Annotation more info
involved_in chloride transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in monoatomic ion transmembrane transport	TAS Traceable Author Statement more info
involved_in proteolysis	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in anchoring junction	IEA Inferred from Electronic Annotation more info
located_in basal plasma membrane	IEA Inferred from Electronic Annotation more info
located_in cell junction	IDA Inferred from Direct Assay more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in extracellular region	IEA Inferred from Electronic Annotation more info
located_in nuclear membrane	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: calcium-activated chloride channel regulator 2

Names: CLCA family member 2, chloride channel regulator; calcium-activated chloride channel protein 3; chloride channel, calcium activated, family member 2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_006536.7 → NP_006527.1 calcium-activated chloride channel regulator 2 preproprotein

See identical proteins and their annotated locations for NP_006527.1

Status: REVIEWED

Source sequence(s)

BC041096, DC417810

Consensus CDS

CCDS708.1

UniProtKB/Swiss-Prot

A8K2T3, Q9UQC9, Q9Y6N2

Related

ENSP00000359596.4, ENST00000370565.5

Conserved Domains (1) summary

cl26751
Location:33 → 896

CLCA; Calcium-activated chloride channel

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000001.11 Reference GRCh38.p14 Primary Assembly

Range

86424171..86456553

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011542448.4 → XP_011540750.1 calcium-activated chloride channel regulator 2 isoform X1

Conserved Domains (3) summary

cd00198
Location:312 → 466

vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...

pfam08434
Location:33 → 571

CLCA; Calcium-activated chloride channel

cl01053
Location:77 → 119

SGNH_hydrolase; SGNH_hydrolase, or GDSL_hydrolase, is a diverse family of lipases and esterases. The tertiary fold of the enzyme is substantially different from that of the alpha/beta hydrolase family and unique among all known hydrolases; its active site closely ...