Clcn1 chloride channel, voltage-sensitive 1 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Clcn1provided by MGI
Official Full Name: chloride channel, voltage-sensitive 1provided by MGI
Primary source: MGI:MGI:88417
See related: Ensembl:ENSMUSG00000029862 AllianceGenome:MGI:88417
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: adr; mto; Clc1; Clc-1; SMCC1; nmf355; myotonia
Summary: Predicted to enable protein homodimerization activity and voltage-gated chloride channel activity. Acts upstream of or within chloride transport and neuronal action potential propagation. Located in sarcolemma. Is expressed in several structures, including central nervous system; early conceptus; heart; oocyte; and skeletal musculature. Used to study myotonia congenita. Human ortholog(s) of this gene implicated in Becker disease; Thomsen disease; and myotonia congenita. Orthologous to human CLCN1 (chloride voltage-gated channel 1). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Biased expression in mammary gland adult (RPKM 3.1), cerebellum adult (RPKM 2.5) and 12 other tissues See more
Orthologs: human all
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Genomic context

Location:: 6 B2.1; 6 20.57 cM

Exon count:: 25

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	6	NC_000072.7 (42263552..42292693)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	6	NC_000072.6 (42284851..42315764)

Chromosome 6 - NC_000072.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Systemic therapy in an RNA toxicity mouse model with an antisense oligonucleotide therapy targeting a non-CUG sequence within the DMPK 3'UTR RNA.
Title: Systemic therapy in an RNA toxicity mouse model with an antisense oligonucleotide therapy targeting a non-CUG sequence within the DMPK 3'UTR RNA.
Data show that Muscleblind-like 1 (Mbnl1) and Muscleblind-Like 3 (Mbnl3) bind skeletal muscle chloride channel CIC-1 (Clc-1) mRNA.
Title: Muscleblind-Like 1 and Muscleblind-Like 3 Depletion Synergistically Enhances Myotonia by Altering Clc-1 RNA Translation.
Sex hormones at high concentration can rapidly modulate ClC-1 in mouse skeletal muscle fibers in vitro.
Title: Nongenomic actions of progesterone and 17β-estradiol on the chloride conductance of skeletal muscle.
Myotonia (delayed muscle relaxation) is the most commonly observed symptom in DM1 patients and is caused by aberrant splicing of the skeletal muscle chloride channel (CLCN1) gene
Title: Manumycin A corrects aberrant splicing of Clcn1 in myotonic dystrophy type 1 (DM1) mice.
Myotonia in adult human skeletal actin transgenic mice may be explained on the basis of a mosaic expression of ClC-1 channels in different fibres and/or on alterations of other conductances.
Title: Age-dependent chloride channel expression in skeletal muscle fibres of normal and HSA(LR) myotonic mice.
The expression of the muscle chloride channel, ClC-1, in Huntington disease muscle was compromised by improper splicing and a corresponding reduction in total Clcn1 (gene for ClC-1) mRNA.
Title: Huntington disease skeletal muscle is hyperexcitable owing to chloride and potassium channel dysfunction.
the majority of functional ClC-1 channels localize to the sarcolemma and provide essential insight into the basis of myofiber excitability in normal and diseased skeletal muscle.
Title: Sarcolemmal-restricted localization of functional ClC-1 channels in mouse skeletal muscle.
These observations indicate that the myotonia and chloride channelopathy observed in DM both result from abnormal alternative splicing of ClC-1
Title: Correction of ClC-1 splicing eliminates chloride channelopathy and myotonia in mouse models of myotonic dystrophy.
genetic CLC-1 chloride channel deficiency in mice not only produces myotonia but also substantially worsens the isotonic contractile performance of diaphragm muscle.
Title: Isotonic contractile impairment due to genetic CLC-1 chloride channel deficiency in myotonic mouse diaphragm muscle.
The A331T mutation causes an unprecedented alteration of ClC-1 gating and reveals novel processes defining transitions between open and closed states in ClC chloride channels
Title: The myotonia congenita mutation A331T confers a novel hyperpolarization-activated gate to the muscle chloride channel ClC-1.

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Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Chemically induced (ENU) (10) 1 citation
Endonuclease-mediated (2) 1 citation
Spontaneous (5) 1 citation

General gene information

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Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables protein homodimerization activity	ISO Inferred from Sequence Orthology more info
enables protein homodimerization activity	ISS Inferred from Sequence or Structural Similarity more info
enables voltage-gated chloride channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables voltage-gated chloride channel activity	ISO Inferred from Sequence Orthology more info
enables voltage-gated chloride channel activity	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in chloride transmembrane transport	ISO Inferred from Sequence Orthology more info
involved_in chloride transmembrane transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in chloride transport	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within chloride transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in chloride transport	ISO Inferred from Sequence Orthology more info
involved_in muscle contraction	ISO Inferred from Sequence Orthology more info
involved_in muscle contraction	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within neuronal action potential propagation	IMP Inferred from Mutant Phenotype more info	PubMed

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	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in sarcolemma	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: chloride channel protein 1

Names: arrested development of righting response; chloride channel protein, skeletal muscle

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.

mRNA and Protein(s)

NM_013491.4 → NP_038519.1 chloride channel protein 1

See identical proteins and their annotated locations for NP_038519.1

Status: VALIDATED

Source sequence(s)

AC153915

Consensus CDS

CCDS39471.1

UniProtKB/Swiss-Prot

Q64347, Q8BZ41, Q9QVY5

UniProtKB/TrEMBL

F6QI82

Related

ENSMUSP00000031894.7, ENSMUST00000031894.13

Conserved Domains (4) summary

cd03683
Location:117 → 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 ...

cd04591
Location:827 → 875

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 ...

pfam00654
Location:170 → 571

Voltage_CLC; Voltage gated chloride channel

cl15354
Location:610 → 665

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_176868.1 RNA Sequence

Status: VALIDATED

Source sequence(s)

AC153915

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000072.7 Reference GRCm39 C57BL/6J

Range

42263552..42292693

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_036165796.1 → XP_036021689.1 chloride channel protein 1 isoform X1

UniProtKB/TrEMBL

Q3TTA5

Conserved Domains (3) summary

cd03683
Location:28 → 362

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:380 → 596

CBS_pair_SF; CBS repeat [structural motif]

cl15354
Location:375 → 645

CBS_pair_SF; Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains superfamily
XM_036165798.1 → XP_036021691.1 chloride channel protein 1 isoform X2

UniProtKB/TrEMBL

Q3TTA5

Conserved Domains (3) summary

cl02915
Location:1 → 254

Voltage_gated_ClC; CLC voltage-gated chloride channel. The ClC chloride channels catalyse the selective flow of Cl- ions across cell membranes, thereby regulating electrical excitation in skeletal muscle and the flow of salt and water across epithelial barriers. This ...

cd02205
Location:272 → 488

CBS_pair_SF; CBS repeat [structural motif]

cl15354
Location:267 → 537

CBS_pair_SF; Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains superfamily
XM_006505476.4 → XP_006505539.1 chloride channel protein 1 isoform X2

UniProtKB/TrEMBL

Q3TTA5

Conserved Domains (3) summary

cl02915
Location:1 → 254

Voltage_gated_ClC; CLC voltage-gated chloride channel. The ClC chloride channels catalyse the selective flow of Cl- ions across cell membranes, thereby regulating electrical excitation in skeletal muscle and the flow of salt and water across epithelial barriers. This ...

cd02205
Location:272 → 488

CBS_pair_SF; CBS repeat [structural motif]

cl15354
Location:267 → 537

CBS_pair_SF; Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains superfamily
XM_036165797.1 → XP_036021690.1 chloride channel protein 1 isoform X2

UniProtKB/TrEMBL

Q3TTA5

Conserved Domains (3) summary

cl02915
Location:1 → 254

Voltage_gated_ClC; CLC voltage-gated chloride channel. The ClC chloride channels catalyse the selective flow of Cl- ions across cell membranes, thereby regulating electrical excitation in skeletal muscle and the flow of salt and water across epithelial barriers. This ...

cd02205
Location:272 → 488

CBS_pair_SF; CBS repeat [structural motif]

cl15354
Location:267 → 537

CBS_pair_SF; Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains superfamily