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

    Gene ID: 1180, updated on 10-Dec-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
    mouse all
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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_2024_08 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (143316111..143352083)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (144671527..144707513)
    RS_2024_09 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. Clinical and molecular diagnosis of a Costa Rican family with autosomal recessive myotonia congenita (Becker disease) carrying a new mutation in the CLCN1 gene. Morales F, et al. Rev Biol Trop, 2008 Mar. PMID 18624224
    2. Functional complementation of truncated human skeletal-muscle chloride channel (hClC-1) using carboxyl tail fragments. Wu W, et al. Biochem J, 2006 Apr 1. PMID 16321142, Free PMC Article
    3. Roles of K149, G352, and H401 in the channel functions of ClC-0: testing the predictions from theoretical calculations. Zhang XD, et al. J Gen Physiol, 2006 Apr. PMID 16567465, Free PMC Article
    4. Activity-induced weakness in recessive myotonia congenita with a novel (696+1G>A) mutation. McKay OM, et al. Clin Neurophysiol, 2006 Sep. PMID 16854622
    5. Functional characterization of CLCN1 mutations in Taiwanese patients with myotonia congenita via heterologous expression. Lin MJ, et al. Biochem Biophys Res Commun, 2006 Dec 29. PMID 17097617

    See all (139) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Clinical and genetic characteristics of myotonia congenita in Chinese population.
      Title: Clinical and genetic characteristics of myotonia congenita in Chinese population.
    2. [A pedigree of myotonia congenita with a novel mutation p.F343C of the CLCN1 gene].
      Title: [A pedigree of myotonia congenita with a novel mutation p.F343C of the CLCN1 gene].
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    8. Mutation spectrum and health status in skeletal muscle channelopathies in Japan.
      Title: Mutation spectrum and health status in skeletal muscle channelopathies in Japan.
    9. 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.
    10. 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.
    Submit: New GeneRIF Correction See all GeneRIFs (102)

    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)

    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
    located_in T-tubule IEA
    Inferred from Electronic Annotation
    more info
    		  
    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
    		  

    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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    NEW Try the new Transcript table

    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_2024_08

    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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