CLCN1 chloride channel, voltage-sensitive 1 [Homo sapiens] - Gene

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Summary

Official Symbol: CLCN1provided by HGNC
Official Full Name: chloride channel, voltage-sensitive 1provided by HGNC
Primary source: HGNC:2019
See related: Ensembl:ENSG00000188037; HPRD:00320; MIM:118425; Vega:OTTHUMG00000152695
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; MGC138361; MGC142055
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]

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Genomic context

Location :: 7q35

Sequence :: Chromosome: 7; NC_000007.13 (143013219..143049097)

See CLCN1 in Epigenomics, MapViewer

Chromosome 7 - NC_000007.13 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

study describes a large Brazilian consanguineous kindred with 3 clinically affected patients with a Thomsen myotonia phenotype; they carry a novel homozygous nonsense mutation in the CLCN1 gene (K248X); none of the 6 heterozygote carriers show any sign...
Title: Thomsen or Becker myotonia? A novel autosomal recessive nonsense mutation in the CLCN1 gene associated with a mild phenotype.
Mutations in CLCN1 contributes to the pronounced variability in the myotonic phenotype.
Title: Myotonia congenita and myotonic dystrophy in the same family: coexistence of a CLCN1 mutation and expansion in the CNBP (ZNF9) gene.
Identified a novel p.N440K sodium channel mutation that is located at the inner end of segment S6 of repeat I.
Title: A novel N440K sodium channel mutation causes myotonia with exercise-induced weakness--exclusion of CLCN1 exon deletion/duplication by MLPA.
Our data showed that slow activation gating of P480T ClC-1 mutation impaired the increment of chloride conductance during repetitive depolarization
Title: A CLCN1 mutation in dominant myotonia congenita impairs the increment of chloride conductance during repetitive depolarization.
sequencing of CLCN1 gene in 2 families with myotonia congenita revealed heterozygous mutation (892G>A, resulting in A298T) in 1 family and compound heterozygous mutations (782A>G, resulting in Y261C;1679T>C, resulting in M560T)in the other family
Title: Novel chloride channel gene mutations in two unrelated Chinese families with myotonia congenita.
Closure of the common gate in ClC-1 channels is accompanied by a separation of the carboxyl-termini, whereas, with opening, the carboxyl-termini approach each other more closely.
Title: Movement of hClC-1 C-termini during common gating and limits on their cytoplasmic location.
A novel p.L2871 mutation in the CLCN1 gene is described in a Honduran boy with myotonia congenita; his unaffected father carries the same mutation, most likely reflecting autosomal-recessive myotonia congenita.
Title: Novel CLCN1 mutation in carbamazepine-responsive myotonia congenita.
hClC-1 mutants expressed in whole-cell patch-clamped HEK293 cells showed that elimination of the carboxyl side chain in the E232Q mutation prevents fast gate closure at all voltages but common gating is also eliminated.
Title: Inter-subunit communication and fast gate integrity are important for common gating in hClC-1.
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.
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.

Submit: New GeneRIF Correction See all (48)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

Thomsen disease, autosomal dominant

MIM: 160800

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description
NT_007914.14	NP_612482.2	SP1		BIND	PubMed	p-CLCN1 interacts with Sp1.
P35523	P35523	CLCN1		HPRD	PubMed

Function	Evidence Code	Pubs
chloride channel activity	TAS Traceable Author Statement more info	PubMed
voltage-gated chloride channel activity	IEA Inferred from Electronic Annotation more info
voltage-gated ion channel activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
chloride transport	TAS Traceable Author Statement more info	PubMed
ion transport	IEA Inferred from Electronic Annotation more info
muscle contraction	TAS Traceable Author Statement more info	PubMed
neuronal action potential propagation	IEA Inferred from Electronic Annotation more info
transmembrane transport	IEA Inferred from Electronic Annotation more info
transport	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
chloride channel complex	IEA Inferred from Electronic Annotation more info
integral to plasma membrane	TAS Traceable Author Statement more info	PubMed
membrane	IEA Inferred from Electronic Annotation more info
sarcolemma	IEA Inferred from Electronic Annotation more info

General protein information

Preferred Names: chloride channel protein 1

Names: chloride channel protein 1; clC-1; chloride channel 1, skeletal muscle; chloride channel protein, skeletal muscle

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NCBI Reference Sequences (RefSeq)

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_009815.1 RefSeqGene

Range

5001..40879

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000083.2 → NP_000074.2 chloride channel protein 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the functional protein.

Source sequence(s)

AC073342, BC112156, Z25884

Consensus CDS

CCDS5881.1

UniProtKB/Swiss-Prot

P35523

Related

ENSP00000339867, OTTHUMP00000202223, ENST00000343257, OTTHUMT00000327420

Conserved Domains (4) summary

cd04591
Location:821 – 869
Blast Score: 154

CBS_pair_EriC_assoc_euk_bac; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains in the EriC CIC-type chloride channels in eukaryotes and bacteria. These ion channels are proteins with a seemingly simple task of allowing the passive flow of ...

cd03683
Location:117 – 592
Blast Score: 1550

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 ...

pfam00654
Location:170 – 571
Blast Score: 603

Voltage_CLC; Voltage gated chloride channel

cl15354
Location:610 – 681
Blast Score: 85

CBS_pair; The CBS domain, named after human CBS, is a small domain originally identified in cystathionine beta-synthase and is subsequently found in a wide range of different proteins. CBS domains usually occur in tandem repeats. They associate to form a so-called ...

RNA

NR_046453.1 RNA Sequence

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, BC143796

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000007.13 Reference GRCh37.p5 Primary Assembly

Range

143013219..143049097

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000139.1 Alternate HuRef

Range

137350584..137386478

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CRA_TCAGchr7v2

Genomic

AC_000068.1 Alternate CRA_TCAGchr7v2

Range

142415337..142451223

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC073342.3 (132806..165868)	None
genomic	AC093673.4	AAS07500.1
genomic	CH236959.1	EAL23786.1
genomic	CH471198.2	EAW51858.1
		EAW51859.1
genomic	L08263.1	None
genomic	Z25587.1	CAA80996.1
genomic	Z25752.1	None
genomic	Z25753.1	CAB56792.1
genomic	Z25757.1	None
genomic	Z25760.1	None
genomic	Z25762.1	None
genomic	Z25768.1	CAB56814.1
genomic	Z25872.1	None
mRNA	AY103154.1	None
mRNA	AY103155.1	None
mRNA	AY103156.1	None
mRNA	BC112156.1	AAI12157.1
mRNA	BC113495.1	AAI13496.1
mRNA	BC143796.1	None
mRNA	M97820.1	None
mRNA	Z25884.1	CAA81103.1
other-genetic	BC111586.2	AAI11587.1