Clcn2 chloride channel, voltage-sensitive 2 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Clcn2provided by MGI
Official Full Name: chloride channel, voltage-sensitive 2provided by MGI
Primary source: MGI:MGI:105061
See related: Ensembl:ENSMUSG00000022843 AllianceGenome:MGI:105061
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: Clc2; ClC-2; nmf240
Summary: Enables voltage-gated chloride channel activity. Acts upstream of or within cell differentiation involved in salivary gland development and retina development in camera-type eye. Predicted to be located in dendrite; perikaryon; and plasma membrane. Predicted to be part of chloride channel complex. Predicted to be integral component of plasma membrane. Is expressed in several structures, including central nervous system; gonad; hindlimb phalanx; notochord; and visual system. Used to study leukodystrophy. Human ortholog(s) of this gene implicated in idiopathic generalized epilepsy 11 and primary hyperaldosteronism. Orthologous to human CLCN2 (chloride voltage-gated channel 2). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Broad expression in colon adult (RPKM 62.6), adrenal adult (RPKM 45.6) and 23 other tissues See more
Orthologs: human all
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Genomic context

Location:: 16 A3- B1; 16 12.5 cM

Exon count:: 26

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	16	NC_000082.7 (20521185..20536496, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	16	NC_000082.6 (20702435..20717746, complement)

Chromosome 16 - NC_000082.7 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: 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?

Regulation of ClC-2 Chloride Channel Proteostasis by Molecular Chaperones: Correction of Leukodystrophy-Associated Defect.
Title: Regulation of ClC-2 Chloride Channel Proteostasis by Molecular Chaperones: Correction of Leukodystrophy-Associated Defect.
CUL4-DDB1-CRBN E3 Ubiquitin Ligase Regulates Proteostasis of ClC-2 Chloride Channels: Implication for Aldosteronism and Leukodystrophy.
Title: CUL4-DDB1-CRBN E3 Ubiquitin Ligase Regulates Proteostasis of ClC-2 Chloride Channels: Implication for Aldosteronism and Leukodystrophy.
a role of ClC-2 in normal aldosterone production beyond the observed pathophysiology, is reported.
Title: Elevated aldosterone and blood pressure in a mouse model of familial hyperaldosteronism with ClC-2 mutation.
knock-in mice expressing a constitutively open ClC-2 Cl- channel increases the chloride conductance of zona glomerulosa cells, provoking a strong depolarization. Clcn2op mice display typical features of human primary aldosteronism, including high serum aldosterone in the presence of low renin activity, marked hypertension and hypokalemia.
Title: Pathogenesis of hypertension in a mouse model for human CLCN2 related hyperaldosteronism.
ClC-2 knockout results in less differentiated colonic crypts and increased tumorigenicity associated with colitis via dysregulation of AJ proteins.
Title: Knockout of ClC-2 reveals critical functions of adherens junctions in colonic homeostasis and tumorigenicity.
High fat diet -treated mice lacking ClC-2 showed inhibited hepatic lipid accumulation via regulating lipid metabolism through decreasing sterol regulatory element binding protein (SREBP)-1c expression and its downstream targeting enzymes such as fatty acid synthase (FAS), HMG-CoA reductase (HMGCR) and acetyl-Coenzyme A carboxylase (ACCalpha).
Title: Lack of ClC-2 Alleviates High Fat Diet-Induced Insulin Resistance and Non-Alcoholic Fatty Liver Disease.
Genetic ablation of ClC-2 resulted in reduced gastric gland region, reduced parietal cell number, reduced H/K ATPase, reduced tubulovesicles and reduced stimulated acid secretion.
Title: Genetic Ablation of the ClC-2 Cl- Channel Disrupts Mouse Gastric Parietal Cell Acid Secretion.
Data indicate that membrane protein MLC1 is crucial for proper localization of adhesion molecule GlialCAM and chloride channel ClC-2, and for changing ClC-2 currents.
Title: Disrupting MLC1 and GlialCAM and ClC-2 interactions in leukodystrophy entails glial chloride channel dysfunction.
Loss of ClC-2 is associated with increased development of DSS-induced colitis.
Title: Chloride channel ClC-2 is a key factor in the development of DSS-induced murine colitis.
fast gate protonation was V(m) and Cl(-) independent and the equilibrium constant for closed-open transition of unprotonated channels was facilitated by elevated [Cl(-)](i) in a V(m)-dependent manner
Title: Sequential interaction of chloride and proton ions with the fast gate steer the voltage-dependent gating in ClC-2 chloride channels.

Submit: New GeneRIF Correction See all GeneRIFs (22)

Variation

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Alleles

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

Targeted (5) 1 citation
Chemically induced (ENU) (2) 1 citation
Endonuclease-mediated (3) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables chloride channel activity	IEA Inferred from Electronic Annotation more info
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
enables voltage-gated chloride channel activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within acinar cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cell differentiation involved in salivary gland development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in chloride transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in chloride transport	ISO Inferred from Sequence Orthology more info
involved_in lung development	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within monoatomic ion transmembrane transport	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within monoatomic ion transport	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of oligodendrocyte differentiation	ISO Inferred from Sequence Orthology more info
involved_in regulation of aldosterone biosynthetic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within retina development in camera-type eye	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in transmembrane transport	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of chloride channel complex	IEA Inferred from Electronic Annotation more info
located_in dendrite	ISO Inferred from Sequence Orthology more info
located_in membrane	IEA Inferred from Electronic Annotation more info
part_of monoatomic ion channel complex	IEA Inferred from Electronic Annotation more info
located_in perikaryon	ISO Inferred from Sequence Orthology 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

General protein information

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Preferred Names: chloride channel protein 2

Names: chloride channel 2

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_001416768.1 → NP_001403697.1 chloride channel protein 2 isoform 2

Status: VALIDATED

Source sequence(s)

AC087898, CT010490

Related

ENSMUST00000148131.8
NM_001416769.1 → NP_001403698.1 chloride channel protein 2 isoform 3

Status: VALIDATED

Source sequence(s)

AC087898, CT010490

Related

ENSMUST00000153075.8
NM_001416770.1 → NP_001403699.1 chloride channel protein 2 isoform 4

Status: VALIDATED

Source sequence(s)

CT010490
NM_009900.3 → NP_034030.2 chloride channel protein 2 isoform 1

See identical proteins and their annotated locations for NP_034030.2

Status: VALIDATED

Source sequence(s)

AC087898, CT010490

Consensus CDS

CCDS28057.1

UniProtKB/Swiss-Prot

Q0VBC2, Q9R0A1, Q9WUJ9

UniProtKB/TrEMBL

A9C437

Related

ENSMUSP00000007207.9, ENSMUST00000007207.15

Conserved Domains (3) summary

cd03683
Location:98 → 575

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:800 → 848

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:151 → 554

Voltage_CLC; Voltage gated chloride channel

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_000082.7 Reference GRCm39 C57BL/6J

Range

20521185..20536496 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006521749.5 → XP_006521812.1 chloride channel protein 2 isoform X2

Conserved Domains (2) summary

cl02915
Location:15 → 309

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 ...

cd04591
Location:321 → 582

CBS_pair_voltage-gated_CLC_euk_bac; Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the voltage gated CLC (chloride channel) in eukaryotes and bacteria
XM_030248952.2 → XP_030104812.1 chloride channel protein 2 isoform X2

Conserved Domains (2) summary

cl02915
Location:15 → 309

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 ...

cd04591
Location:321 → 582

CBS_pair_voltage-gated_CLC_euk_bac; Two tandem repeats of the cystathionine beta-synthase (CBS pair) domains associated with the voltage gated CLC (chloride channel) in eukaryotes and bacteria