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

Summary

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

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_000007.14 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

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?

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.
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.
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.
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.
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.
Mutation spectrum and health status in skeletal muscle channelopathies in Japan.
Title: Mutation spectrum and health status in skeletal muscle channelopathies in Japan.
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.
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.
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.
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

Associated conditions

Description	Tests
Congenital myotonia, autosomal dominant form MedGen: C2936781 OMIM: 160800 GeneReviews: Myotonia Congenita	Compare labs
Congenital myotonia, autosomal recessive form MedGen: C0751360 OMIM: 255700 GeneReviews: Myotonia Congenita	Compare labs

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

GDB:374988 (e-PCR)
- UniSTS:156970

GDB:375007 (e-PCR)
- UniSTS:156971

GDB:375010 (e-PCR)
- UniSTS:156972

GDB:375013 (e-PCR)
- UniSTS:156973

GDB:375016 (e-PCR)
- UniSTS:156974

GDB:375019 (e-PCR)
- UniSTS:156975

GDB:375022 (e-PCR)
- UniSTS:156976

GDB:375025 (e-PCR)
- UniSTS:156977

GDB:375028 (e-PCR)
- UniSTS:156978

GDB:375031 (e-PCR)
- UniSTS:156979

GDB:375034 (e-PCR)
- UniSTS:156980

GDB:375037 (e-PCR)
- UniSTS:156981

GDB:375040 (e-PCR)
- UniSTS:156982

GDB:375043 (e-PCR)
- UniSTS:156983

GDB:375046 (e-PCR)
- UniSTS:156984

GDB:375049 (e-PCR)
- UniSTS:156985

GDB:375052 (e-PCR)
- UniSTS:156986

GDB:375055 (e-PCR)
- UniSTS:156987

GDB:375058 (e-PCR)
- UniSTS:156988

GDB:375061 (e-PCR)
- UniSTS:156989

GDB:375064 (e-PCR)
- UniSTS:156990

GDB:375067 (e-PCR)
- UniSTS:156991

GDB:677002 (e-PCR)
- UniSTS:158574

GDB:677007 (e-PCR)
- UniSTS:158575

GDB:677010 (e-PCR)
- UniSTS:158576

GDB:677013 (e-PCR)
- UniSTS:158577

GDB:677018 (e-PCR)
- UniSTS:158578

GDB:677053 (e-PCR)
- UniSTS:158581

GDB:677067 (e-PCR)
- UniSTS:158582

CLCN1 (e-PCR)
- UniSTS:44662

GDB:1317254 (e-PCR)
- UniSTS:27511

GDB:677070 (e-PCR)
- UniSTS:158583

GDB:677073 (e-PCR)
- UniSTS:158584

GDB:677079 (e-PCR)
- UniSTS:158585

GDB:677082 (e-PCR)
- UniSTS:158586

GDB:677085 (e-PCR)
- UniSTS:158587

GDB:677099 (e-PCR)
- UniSTS:158590

GDB:677102 (e-PCR)
- UniSTS:158591

GDB:677105 (e-PCR)
- UniSTS:158592

GDB:677108 (e-PCR)
- UniSTS:158593

GDB:677111 (e-PCR)
- UniSTS:158594

GDB:677114 (e-PCR)
- UniSTS:158595

GDB:677117 (e-PCR)
- UniSTS:158596

RH71311 (e-PCR)
- UniSTS:37032

GDB:373603 (e-PCR)
- UniSTS:156911

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

NG_009815.2 RefSeqGene

Range

4986..40958

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

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