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CLCN1 chloride voltage-gated channel 1 [ Homo sapiens (human) ]

Gene ID: 1180, updated on 11-Apr-2024

Summary

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Official Symbol
CLCN1provided by HGNC
Official Full Name
chloride voltage-gated channel 1provided by HGNC
Primary source
HGNC:HGNC:2019
See related
Ensembl:ENSG00000188037 MIM:118425; AllianceGenome:HGNC:2019
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
CLC1
Summary
The CLCN family of voltage-dependent chloride channel genes comprises nine members (CLCN1-7, Ka and Kb) which demonstrate quite diverse functional characteristics while sharing significant sequence homology. The protein encoded by this gene regulates the electric excitability of the skeletal muscle membrane. Mutations in this gene cause two forms of inherited human muscle disorders: recessive generalized myotonia congenita (Becker) and dominant myotonia (Thomsen). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]
Expression
Low expression observed in reference dataset See more
Orthologs
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Genomic context

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See CLCN1 in Genome Data Viewer
Location:
7q34
Exon count:
23
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (143316111..143352083)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (144671527..144707513)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (143013204..143049176)

Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene caspase 2 Neighboring gene RNA, 7SL, cytoplasmic 481, pseudogene Neighboring gene histidine triad nucleotide binding protein 1 pseudogene 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18721 Neighboring gene Sharpr-MPRA regulatory region 4117 Neighboring gene family with sequence similarity 131 member B Neighboring gene FAM131B antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26792 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:143077234-143078134 Neighboring gene FAM131B antisense RNA 2

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. Functional analysis of the F337C mutation in the CLCN1 gene associated with dominant myotonia congenita reveals an alteration of the macroscopic conductance and voltage dependence. Jehasse K, et al. Mol Genet Genomic Med, 2021 Feb. PMID 33507632, Free PMC Article
  2. Association of Three Different Mutations in the CLCN1 Gene Modulating the Phenotype in a Consanguineous Family with Myotonia Congenita. Souza LS, et al. J Mol Neurosci, 2021 Nov. PMID 33464536
  3. Recessive myotonia congenita caused by a homozygous splice site variant in CLCN1 gene: a case report. Sparber P, et al. BMC Med Genet, 2020 Oct 22. PMID 33092578, Free PMC Article
  4. The analysis of myotonia congenita mutations discloses functional clusters of amino acids within the CBS2 domain and the C-terminal peptide of the ClC-1 channel. Altamura C, et al. Hum Mutat, 2018 Sep. PMID 29935101
  5. [Analysis of CLCN1 gene mutations in a family affected with myotonia congenita]. Jing F, et al. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 2018 Jun 10. PMID 29896741

See all (137) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Coexistence of SCN4A and CLCN1 mutations in a family with atypical myotonic features: A clinical and functional study.
    Title: Coexistence of SCN4A and CLCN1 mutations in a family with atypical myotonic features: A clinical and functional study.
  2. Sequence CLCN1 and SCN4A genes in patients with nondystrophic myotonia in Chinese people.
    Title: Sequence CLCN1 and SCN4A genes in patients with nondystrophic myotonia in Chinese people.
  3. Clinical and molecular characterization of five Chinese patients with autosomal recessive osteopetrosis.
    Title: Clinical and molecular characterization of five Chinese patients with autosomal recessive osteopetrosis.
  4. Association of Three Different Mutations in the CLCN1 Gene Modulating the Phenotype in a Consanguineous Family with Myotonia Congenita.
    Title: Association of Three Different Mutations in the CLCN1 Gene Modulating the Phenotype in a Consanguineous Family with Myotonia Congenita.
  5. Functional and Structural Characterization of ClC-1 and Nav1.4 Channels Resulting from CLCN1 and SCN4A Mutations Identified Alone and Coexisting in Myotonic Patients.
    Title: Functional and Structural Characterization of ClC-1 and Na(v)1.4 Channels Resulting from CLCN1 and SCN4A Mutations Identified Alone and Coexisting in Myotonic Patients.
  6. Mutation spectrum and health status in skeletal muscle channelopathies in Japan.
    Title: Mutation spectrum and health status in skeletal muscle channelopathies in Japan.
  7. Non-dystrophic myotonia Chilean cohort with predominance of the SCN4A Gly1306Glu variant.
    Title: Non-dystrophic myotonia Chilean cohort with predominance of the SCN4A Gly1306Glu variant.
  8. Functional analysis of the F337C mutation in the CLCN1 gene associated with dominant myotonia congenita reveals an alteration of the macroscopic conductance and voltage dependence.
    Title: Functional analysis of the F337C mutation in the CLCN1 gene associated with dominant myotonia congenita reveals an alteration of the macroscopic conductance and voltage dependence.
  9. Recessive myotonia congenita caused by a homozygous splice site variant in CLCN1 gene: a case report.
    Title: Recessive myotonia congenita caused by a homozygous splice site variant in CLCN1 gene: a case report.
  10. Twenty-eight different pathogenic variants were found in the CLCN1 gene, of which 21 were known mutations and seven not described. A diagnostic yield of 51% was achieved; of which 88% had pathogenic variants in CLCN1 and 12% in SCN4A.
    Title: Myotonia congenita: mutation spectrum of CLCN1 in Spanish patients.
Submit: New GeneRIF Correction See all GeneRIFs (100)

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)

Genotypes

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC138361, MGC142055

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein homodimerization activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables voltage-gated chloride channel activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables voltage-gated chloride channel activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Process Evidence Code Pubs
involved_in chloride transmembrane transport IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in chloride transport IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in muscle contraction IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in neuronal action potential propagation IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
part_of chloride channel complex 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 IC
Inferred by Curator
more info
 PubMed 
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
  
located_in sarcolemma IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
chloride channel protein 1
Names
chloride channel 1, skeletal muscle
chloride channel protein, skeletal muscle
chloride channel, voltage-sensitive 1
clC-1

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_009815.2 RefSeqGene

    Range
    4986..40958
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000083.3 → NP_000074.3  chloride channel protein 1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the functional protein.
    Source sequence(s)
    AC073342, AC093673
    Consensus CDS
    CCDS5881.1
    UniProtKB/Swiss-Prot
    A4D2H5, P35523, Q2M202
    UniProtKB/TrEMBL
    A0A3B3IU72
    Related
    ENSP00000339867.2, ENST00000343257.7
    Conserved Domains (3) summary
    cd03683
    Location:131 → 592
    ClC_1_like; ClC-1-like chloride channel proteins. This CD includes isoforms ClC-0, ClC-1, ClC-2 and ClC_K. ClC-1 is expressed in skeletal muscle and its mutation leads to both recessively and dominantly-inherited forms of muscle stiffness or myotonia. ClC-K is ...
    cd02205
    Location:610 → 820
    CBS_pair_SF; CBS repeat [structural motif]
    cl15354
    Location:605 → 869
    CBS_pair_SF; Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains superfamily

RNA

  1. NR_046453.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate splice site and lacks an internal exon 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)
    AC073342, AC093673

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_000007.14 Reference GRCh38.p14 Primary Assembly

    Range
    143316111..143352083
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060931.1 Alternate T2T-CHM13v2.0

    Range
    144671527..144707513
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P35523.3 GenPept UniProtKB/Swiss-Prot:P35523

Gene LinkOut

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