Clcn2 chloride voltage-gated channel 2 [Rattus norvegicus (Norway rat)] - Gene

Summary

Symbol: Clcn2provided by RGD
Full Name: chloride voltage-gated channel 2provided by RGD
Primary source: RGD:2361
See related: EnsemblRapid:ENSRNOG00000001742 AllianceGenome:RGD:2361
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: ClC-2
Summary: Enables voltage-gated chloride channel activity and volume-sensitive chloride channel activity. Involved in several processes, including cellular hypotonic response; positive regulation of oligodendrocyte differentiation; and positive regulation of voltage-gated chloride channel activity. Located in several cellular components, including axon initial segment; dendritic spine membrane; and perikaryon. Used to study cystic fibrosis. 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, Nov 2024]
Expression: Biased expression in Kidney (RPKM 54.8), Brain (RPKM 54.0) and 9 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 11q23

Exon count:: 24

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	11	NC_086029.1 (93702382..93716059)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	11	NC_051346.1 (80197741..80211657)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	11	NC_005110.4 (82862664..82876165)

Chromosome 11 - NC_086029.1 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: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

NEDD4-2 and the CLC-2 channel regulate neuronal excitability in the pathogenesis of mesial temporal lobe epilepsy.
Title: NEDD4-2 and the CLC-2 channel regulate neuronal excitability in the pathogenesis of mesial temporal lobe epilepsy.
ClC-2 and caspase-3 were induced by GDM, which resulted in apoptosis and myelination inhibition. The effect was caused by repressing PI3K-Akt signaling pathway. Application of ClC-2 inhibitor DIDS showed protective effects on cerebral white matter damage stimulated by high glucose concentration.
Title: Activated ClC-2 Inhibits p-Akt to Repress Myelination in GDM Newborn Rats.
ClC-2 is upregulated in pyramidal cells of pilocarpine-treated rats; this involves alpha5 subunit-containing GABA(A) receptor.
Title: ClC-2 contributes to tonic inhibition mediated by α5 subunit-containing GABA(A) receptor in experimental temporal lobe epilepsy.
GABAA receptor-mediated synaptic inputs from basket cells were modulated by ClC-2. Our data reveal a previously unknown cell type-specific regulation of intracellular chloride homeostasis in the perisomatic region of hippocampal pyramidal neurons.
Title: Regulation of fast-spiking basket cell synapses by the chloride channel ClC-2.
functional ClC-2-type Cl(-) channel is expressed in rat rectal surface epithelium, but channel activity may be negligible & thus nonessential for controlling electrogenic Na(+) transport in this surface epithelium under basal physiological conditions.
Title: Functional characterization of a ClC-2-like Cl(-) conductance in surface epithelial cells of rat rectal colon.
The results demonstrate that rat hepatocytes express a ClC-2-like time-dependent inward Cl- channel that could provide a significant depolarizing influence in the hepatocyte.
Title: Contribution of a time-dependent and hyperpolarization-activated chloride conductance to currents of resting and hypotonically shocked rat hepatocytes.
novel deletion variants of ClC-2 due to partial exon 15 skipping may be expressed normally in heart and contribute to the formation of endogenous Cl.ir channels in native cardiac cells
Title: Functional characterization of novel alternatively spliced ClC-2 chloride channel variants in the heart.
ClC-2 may be involved in estrogen-induced Cl(-) transport in rat kidney.
Title: Estrogen modulates ClC-2 chloride channel gene expression in rat kidney.
effect of an N-terminus deletion on voltage-dependent gating; observations are an argument against a ball-and-chain mechanism for this channel
Title: Effect of an N-terminus deletion on voltage-dependent gating of the ClC-2 chloride channel.
ClC-2 possesses a common gate, and part of current increase induced by hyperpolarization represents opening of common gate. Protopore gate and common gate of ClC-2 do not appear to be independent.
Title: The voltage-dependent ClC-2 chloride channel has a dual gating mechanism.

Submit: New GeneRIF Correction See all GeneRIFs (15)

General gene information

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Markers

D11Wox16 (e-PCR)
- UniSTS:518776

RH94517 (e-PCR)
- UniSTS:119765

BF387879 (e-PCR)
- UniSTS:244456

RH129159 (e-PCR)
- UniSTS:212467

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables chloride channel regulator activity	ISO Inferred from Sequence Orthology more info
enables voltage-gated chloride channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables voltage-gated chloride channel activity	IDA Inferred from Direct Assay more info	PubMed
enables voltage-gated chloride channel activity	IEA Inferred from Electronic Annotation 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
enables voltage-gated monoatomic anion channel activity	IDA Inferred from Direct Assay more info	PubMed
enables voltage-gated monoatomic anion channel activity	ISO Inferred from Sequence Orthology more info
enables volume-sensitive chloride channel activity	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
acts_upstream_of_or_within acinar cell differentiation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within cell differentiation involved in salivary gland development	ISO Inferred from Sequence Orthology more info
involved_in cellular hypotonic response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in chloride transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in chloride transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in chloride transport	IDA Inferred from Direct Assay more info	PubMed
involved_in chloride transport	ISO Inferred from Sequence Orthology more info
involved_in lung development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in phagocytosis, engulfment	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of oligodendrocyte differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of voltage-gated chloride channel activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of aldosterone biosynthetic process	ISO Inferred from Sequence Orthology more info
involved_in regulation of aldosterone biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of membrane depolarization during action potential	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of resting membrane potential	IEA Inferred from Electronic Annotation more info
involved_in regulation of resting membrane potential	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within retina development in camera-type eye	ISO Inferred from Sequence Orthology more info
involved_in stabilization of membrane potential	IEA Inferred from Electronic Annotation more info
involved_in stabilization of membrane potential	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in actin cytoskeleton	ISS Inferred from Sequence or Structural Similarity more info
located_in astrocyte end-foot	IDA Inferred from Direct Assay more info	PubMed
located_in astrocyte end-foot	ISO Inferred from Sequence Orthology more info
located_in axon	IEA Inferred from Electronic Annotation more info
located_in axon initial segment	IDA Inferred from Direct Assay more info	PubMed
located_in basolateral plasma membrane	IEA Inferred from Electronic Annotation more info
located_in basolateral plasma membrane	ISO Inferred from Sequence Orthology more info
part_of chloride channel complex	IEA Inferred from Electronic Annotation more info
located_in dendrite	IDA Inferred from Direct Assay more info	PubMed
located_in dendritic spine membrane	IDA Inferred from Direct Assay more info	PubMed
located_in dendritic spine membrane	IEA Inferred from Electronic Annotation more info
located_in myelin sheath	ISO Inferred from Sequence Orthology more info
located_in perikaryon	IDA Inferred from Direct Assay more info	PubMed
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 postsynaptic membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: chloride channel protein 2

Names: chloride channel 2; chloride channel, voltage-sensitive 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_017137.2 → NP_058833.1 chloride channel protein 2

See identical proteins and their annotated locations for NP_058833.1

Status: VALIDATED

Source sequence(s)

X64139

UniProtKB/Swiss-Prot

P35525

UniProtKB/TrEMBL

A6JS86, O54821

Related

ENSRNOP00000050925.3, ENSRNOT00000050927.8

Conserved Domains (3) summary

cd03683
Location:96 → 573

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:799 → 847

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:149 → 552

Voltage_CLC; Voltage gated chloride channel

RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

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

Reference GRCr8

Genomic

NC_086029.1 Reference GRCr8

Range

93702382..93716059

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006248563.5 → XP_006248625.1 chloride channel protein 2 isoform X1

See identical proteins and their annotated locations for XP_006248625.1

UniProtKB/TrEMBL

A0A0A0MXT6, O54822

Related

ENSRNOP00000002376.5, ENSRNOT00000002376.10

Conserved Domains (3) summary

cd03683
Location:96 → 573

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:779 → 827

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:149 → 552

Voltage_CLC; Voltage gated chloride channel
XM_039088239.2 → XP_038944167.1 chloride channel protein 2 isoform X2

UniProtKB/TrEMBL

A0A8L2QXG3

Conserved Domains (2) summary

cd03683
Location:1 → 446

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:458 → 720

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_063270438.1 → XP_063126508.1 chloride channel protein 2 isoform X4
XM_063270437.1 → XP_063126507.1 chloride channel protein 2 isoform X3
XM_039088243.2 → XP_038944171.1 chloride channel protein 2 isoform X6

UniProtKB/TrEMBL

O54823

Conserved Domains (1) summary

cd03683
Location:96 → 471

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 ...
XM_039088240.2 → XP_038944168.1 chloride channel protein 2 isoform X5

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 → 583

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_039088244.2 → XP_038944172.1 chloride channel protein 2 isoform X7

Conserved Domains (2) summary

cl02915
Location:43 → 144

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:156 → 418

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