CLCA4 chloride channel accessory 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CLCA4provided by HGNC
Official Full Name: chloride channel accessory 4provided by HGNC
Primary source: HGNC:HGNC:2018
See related: Ensembl:ENSG00000016602 MIM:616857; AllianceGenome:HGNC:2018
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; CaCC2
Summary: The protein encoded by this gene belongs to the calcium sensitive chloride conductance protein family. To date, all members of this gene family map to the same site on chromosome 1p31-p22 and share high degrees of homology in size, sequence and predicted structure, but differ significantly in their tissue distributions. Alternative splicing results in multiple transcript variants, only one of which is thought to be protein coding. [provided by RefSeq, Dec 2008]
Expression: Biased expression in colon (RPKM 204.3), esophagus (RPKM 195.4) and 1 other tissue See more
Orthologs: all
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Genomic context

Location:: 1p22.3

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (86547078..86580754)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (86387119..86420795)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (87012761..87046437)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Modulation of TMEM16B channel activity by the calcium-activated chloride channel regulator 4 (CLCA4) in human cells.
Title: Modulation of TMEM16B channel activity by the calcium-activated chloride channel regulator 4 (CLCA4) in human cells.
Frameshift Mutations and Loss of Expression of CLCA4 Gene are Frequent in Colorectal Cancers With Microsatellite Instability.
Title: Frameshift Mutations and Loss of Expression of CLCA4 Gene are Frequent in Colorectal Cancers With Microsatellite Instability.
CLCA4 and MS4A12 as the significant gene biomarkers of primary colorectal cancer.
Title: CLCA4 and MS4A12 as the significant gene biomarkers of primary colorectal cancer.
CLCA4 inhibits migration and invasion by suppressing EMT via PI3K/ATK signaling and predicts favorable prognosis of CRC which may help to distinguish potential risk of lymph node metastasis in CRC.
Title: Calcium-Activated Chloride Channel A4 (CLCA4) Plays Inhibitory Roles in Invasion and Migration Through Suppressing Epithelial-Mesenchymal Transition via PI3K/AKT Signaling in Colorectal Cancer.
CLCA4 contributes to migration and invasion by suppressing epithelial-mesenchymal transition via PI3K/ATK signaling and predicts favourable prognosis for hepatocellular carcinoma.
Title: CLCA4 inhibits cell proliferation and invasion of hepatocellular carcinoma by suppressing epithelial-mesenchymal transition via PI3K/AKT signaling.
Six SNPs, c.390C>T (rs190628533), c.1474A>G (rs2231599), c.2105C>G (rs757773924), c.2371A>T) (rs759981524), c.956G>A (rs763334876), and c.895T>C (rs79822589) were identified in the study group of cases in Non-Obstructive Azoospermia but not in control subjects. The allele and genotype frequencies of the six SNPs were not significantly different between the study group and the controls.
Title: Chloride Channel Accessory 4 (CLCA4) Gene Polymorphisms and Non-Obstructive Azoospermia: A Case-Control Study.
CLCA4 and CLCA2 play complementary but distinct roles in epithelial differentiation
Title: Loss of CLCA4 promotes epithelial-to-mesenchymal transition in breast cancer cells.
CLCA4 modulates the capability to express residual chloride secretion in colonic tissue.
Title: CLCA4 variants determine the manifestation of the cystic fibrosis basic defect in the intestine.
CLCA1 and CLCA4 may have roles as modulators of the gastrointestinal basic defect in cystic fibrosis
Title: The CLCA gene locus as a modulator of the gastrointestinal basic defect in cystic fibrosis.

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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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Replication interactions

Interaction	Pubs
Knockdown of chloride channel accessory 4 (CLCA4) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells	PubMed

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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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 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 apical plasma membrane	IEA Inferred from Electronic Annotation more info
located_in extracellular region	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor 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 4

Names: caCC-2; calcium-activated chloride channel family member 4; calcium-activated chloride channel protein 2; chloride channel regulator 4; chloride channel, calcium activated, family member 4; hCLCA4; hCaCC-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_012128.4 → NP_036260.2 calcium-activated chloride channel regulator 4 precursor

See identical proteins and their annotated locations for NP_036260.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript.

Source sequence(s)

AY358470, DA761219

Consensus CDS

CCDS41355.1

UniProtKB/Swiss-Prot

A8MQC9, B7Z1Q5, Q14CN2, Q6UX81, Q9UNF7

Related

ENSP00000359594.3, ENST00000370563.3

Conserved Domains (2) summary

cd00198
Location:305 → 459

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:24 → 909

CLCA; Calcium-activated chloride channel

RNA

NR_024602.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate exon in the 5' coding region, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AK307785, CB851641, DA668017

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

86547078..86580754

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011541015.3 → XP_011539317.1 calcium-activated chloride channel regulator 4 isoform X1

Conserved Domains (2) summary

cd00198
Location:254 → 408

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:2 → 858

CLCA; Calcium-activated chloride channel