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

Gene ID: 1185, updated on 5-Mar-2024

Summary

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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
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Genomic context

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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_000001.11Genomic Context describing neighboring genes Neighboring gene chromosome 1 open reading frame 167 Neighboring gene C1orf167 antisense RNA 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:11847781-11848588 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:11851353-11851865 Neighboring gene methylenetetrahydrofolate reductase Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:11860626-11861224 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:11862804-11863700 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:11863701-11864596 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 272 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 273 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:11865893-11866878 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 178 Neighboring gene NPPA antisense RNA 1 Neighboring gene VISTA enhancer hs2123 Neighboring gene natriuretic peptide A Neighboring gene natriuretic peptide B

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Bibliography

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Related articles in PubMed

  1. Rare Exome Sequence Variants in CLCN6 Reduce Blood Pressure Levels and Hypertension Risk. Yu B, et al. Circ Cardiovasc Genet, 2016 Feb. PMID 26658788, Free PMC Article
  2. Single nucleotide variations in CLCN6 identified in patients with benign partial epilepsies in infancy and/or febrile seizures. Yamamoto T, et al. PLoS One, 2015. PMID 25794116, Free PMC Article
  3. The late endosomal ClC-6 mediates proton/chloride countertransport in heterologous plasma membrane expression. Neagoe I, et al. J Biol Chem, 2010 Jul 9. PMID 20466723, Free PMC Article
  4. Human ClC-6 is a late endosomal glycoprotein that associates with detergent-resistant lipid domains. Ignoul S, et al. PLoS One, 2007 May 30. PMID 17534424, Free PMC Article
  5. A Recurrent Gain-of-Function Mutation in CLCN6, Encoding the ClC-6 Cl(-)/H(+)-Exchanger, Causes Early-Onset Neurodegeneration. Polovitskaya MM, et al. Am J Hum Genet, 2020 Dec 3. PMID 33217309, Free PMC Article

See all (38) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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

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
Genome-wide association study identifies eight loci associated with blood pressure.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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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

Homology

Clone Names

  • KIAA0046

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 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

  1. NG_008766.2 RefSeqGene

    Range
    5002..41941
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. 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

  2. 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

  1. 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

  1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    11806191..11843130
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    11350275..11387211
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. 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.

  2. 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.

  3. 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.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P51797.2 GenPept UniProtKB/Swiss-Prot:P51797

Gene LinkOut

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