CLCN6 chloride voltage-gated channel 6 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CLCN6provided by HGNC
Official Full Name: chloride voltage-gated channel 6provided by HGNC
Primary source: HGNC:HGNC:2024
See related: Ensembl:ENSG00000011021 MIM:602726; AllianceGenome:HGNC:2024
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: CLC-6; CONRIBA
Summary: This gene encodes a member of the voltage-dependent chloride channel protein family. Members of this family can function as either chloride channels or antiporters. This protein is primarily localized to late endosomes and functions as a chloride/proton antiporter. Alternate splicing results in both coding and non-coding variants. Additional alternately spliced variants have been described but their full-length structure is unknown. [provided by RefSeq, Mar 2012]
Expression: Ubiquitous expression in brain (RPKM 13.0), testis (RPKM 10.2) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1p36.22

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (11806191..11843130)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (11350275..11387211)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (11866248..11903187)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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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?

Molecular basis of ClC-6 function and its impairment in human disease.
Title: Molecular basis of ClC-6 function and its impairment in human disease.
Exploring dementia and neuronal ceroid lipofuscinosis genes in 100 FTD-like patients from 6 towns and rural villages on the Adriatic Sea cost of Apulia.
Title: Exploring dementia and neuronal ceroid lipofuscinosis genes in 100 FTD-like patients from 6 towns and rural villages on the Adriatic Sea cost of Apulia.
A Recurrent Gain-of-Function Mutation in CLCN6, Encoding the ClC-6 Cl(-)/H(+)-Exchanger, Causes Early-Onset Neurodegeneration.
Title: A Recurrent Gain-of-Function Mutation in CLCN6, Encoding the ClC-6 Cl(-)/H(+)-Exchanger, Causes Early-Onset Neurodegeneration.
These findings implicate the effect of rare coding variants in CLCN6 in Blood Pressure variation and offer new insights into Blood Pressure regulation.
Title: Rare Exome Sequence Variants in CLCN6 Reduce Blood Pressure Levels and Hypertension Risk.
A non-synonymous single nucleotide variation (SNV) was identified in the voltage-sensitive chloride channel 6 gene.
Title: Single nucleotide variations in CLCN6 identified in patients with benign partial epilepsies in infancy and/or febrile seizures.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
late endosomal ClC-6 mediates proton/chloride countertransport in heterologous plasma membrane expression
Title: The late endosomal ClC-6 mediates proton/chloride countertransport in heterologous plasma membrane expression.
Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
Title: Identification of type 2 diabetes-associated combination of SNPs using support vector machine.
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
differential sorting of endogenous (late endosomal) versus overexpressed (early and recycling endosomal) ClC-6 is reminiscent of that of other late endosomal/lysosomal membrane proteins
Title: Human ClC-6 is a late endosomal glycoprotein that associates with detergent-resistant lipid domains.

Submit: New GeneRIF Correction See all GeneRIFs (11)

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

Associated conditions

Description	Tests
Neurodegeneration, childhood-onset, with hypotonia, respiratory insufficiency, and brain imaging abnormalities MedGen: C5543020 OMIM: 619173 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genome-wide association analysis and fine mapping of NT-proBNP level provide novel insight into the role of the MTHFR-CLCN6-NPPA-NPPB gene cluster. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies eight loci associated with blood pressure. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G30984 (e-PCR)
- UniSTS:67591

CLCN6_3953 (e-PCR)
- UniSTS:462106

MARC_15621-15622:1017176151:1 (e-PCR)
- UniSTS:267844

SHGC-74236 (e-PCR)
- UniSTS:66376

RH44595 (e-PCR)
- UniSTS:59007

SHGC-35004 (e-PCR)
- UniSTS:20616

AL033967 (e-PCR)
- UniSTS:93379

RH70928 (e-PCR)
- UniSTS:53728

G34853 (e-PCR)
- UniSTS:81386

RH25282 (e-PCR)
- UniSTS:87037

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables antiporter activity	TAS Traceable Author Statement more info
enables chloride transmembrane transporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables voltage-gated chloride channel activity	IDA Inferred from Direct Assay more info	PubMed
enables voltage-gated chloride channel activity	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in cell volume homeostasis	NAS Non-traceable Author Statement more info	PubMed
involved_in chloride transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in chloride transport	IDA Inferred from Direct Assay more info	PubMed
involved_in chloride transport	NAS Non-traceable Author Statement more info	PubMed
involved_in monoatomic ion transmembrane transport	TAS Traceable Author Statement more info
involved_in response to mechanical stimulus	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in endosome membrane	TAS Traceable Author Statement more info
is_active_in intracellular membrane-bounded organelle	IBA Inferred from Biological aspect of Ancestor more info
located_in late endosome membrane	IEA Inferred from Electronic Annotation more info
located_in lysosomal membrane	HDA more info	PubMed
located_in membrane	NAS Non-traceable Author Statement more info	PubMed

General protein information

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Preferred Names: H(+)/Cl(-) exchange transporter 6

Names: chloride channel, voltage-sensitive 6; chloride transport protein 6

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.

Genomic

NG_008766.2 RefSeqGene

Range

5002..41941

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001256959.2 → NP_001243888.2 H(+)/Cl(-) exchange transporter 6 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an in-frame exon in the coding region, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.

Source sequence(s)

AL021155, AL953897

Consensus CDS

CCDS57972.1

Related

ENSP00000308367.7, ENST00000312413.10

Conserved Domains (2) summary

cd03685
Location:40 → 566

ClC_6_like; ClC-6-like chloride channel proteins. This CD includes ClC-6, ClC-7 and ClC-B, C, D in plants. Proteins in this family are ubiquitous in eukarotes and their functions are unclear. They are expressed in intracellular organelles membranes. This family ...

cd04591
Location:578 → 834

CBS_pair_voltage-gated_CLC_euk_bac; Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the voltage gated CLC (chloride channel) in eukaryotes and bacteria
NM_001286.5 → NP_001277.2 H(+)/Cl(-) exchange transporter 6 isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) is the longest transcript and encodes the longer isoform (1). This isoform is also known as CLC-6a.

Source sequence(s)

AL021155, AL953897

Consensus CDS

CCDS138.1

UniProtKB/Swiss-Prot

A8K1T4, B4DGT7, F8W9R3, O60818, O60819, O60820, O60821, P51797, P78520, P78521, Q17R81, Q5SNW2, Q5SNW3, Q5SNX1, Q5SNX2, Q5SNX3, Q99427, Q99428, Q99429

Related

ENSP00000234488.9, ENST00000346436.11

Conserved Domains (2) summary

cd03685
Location:49 → 588

ClC_6_like; ClC-6-like chloride channel proteins. This CD includes ClC-6, ClC-7 and ClC-B, C, D in plants. Proteins in this family are ubiquitous in eukarotes and their functions are unclear. They are expressed in intracellular organelles membranes. This family ...

cd04591
Location:600 → 856

CBS_pair_voltage-gated_CLC_euk_bac; Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the voltage gated CLC (chloride channel) in eukaryotes and bacteria

RNA

NR_046428.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate splice site, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AL021155, AL953897

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

11806191..11843130

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060925.1 Alternate T2T-CHM13v2.0

Range

11350275..11387211

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GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_021735.2: Suppressed sequence

Description

NM_021735.2: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
NM_021736.2: Suppressed sequence

Description

NM_021736.2: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
NM_021737.2: Suppressed sequence

Description

NM_021737.2: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.