U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

CLCN2 chloride voltage-gated channel 2 [ Homo sapiens (human) ]

Gene ID: 1181, updated on 11-Jun-2025
Official Symbol
CLCN2provided by HGNC
Official Full Name
chloride voltage-gated channel 2provided by HGNC
Primary source
HGNC:HGNC:2020
See related
Ensembl:ENSG00000114859 MIM:600570; AllianceGenome:HGNC:2020
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
CLC2; ECA2; ECA3; EGI3; EGMA; EJM6; EJM8; FHA2; FHII; CIC-2; EGI11; HALD2; LKPAT; clC-2
Summary
This gene encodes a voltage-gated chloride channel. The encoded protein is a transmembrane protein that maintains chloride ion homeostasis in various cells. Defects in this gene may be a cause of certain epilepsies. Four transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2012]
Expression
Broad expression in testis (RPKM 8.7), colon (RPKM 7.2) and 24 other tissues See more
Orthologs
mouse all
NEW
Try the new Gene table
Try the new Transcript table
See CLCN2 in Genome Data Viewer
Location:
3q27.1
Exon count:
25
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (184346185..184361605, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (187155451..187170873, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (184063973..184079393, complement)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14959 Neighboring gene proteasome 26S subunit ubiquitin receptor, non-ATPase 2 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:184031817-184032317 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:184033042-184033663 Neighboring gene eukaryotic translation initiation factor 4 gamma 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:184045141-184045641 Neighboring gene small nucleolar RNA, C/D box 66 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20908 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:184053938-184054138 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:184055930-184056541 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20909 Neighboring gene family with sequence similarity 131 member A Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:184061884-184062636 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:184062637-184063388 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:184063389-184064141 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:184064142-184064893 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:184077025-184077538 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:184077539-184078050 Neighboring gene uncharacterized LOC124906311 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14964 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14965 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14966 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14967 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20910 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20911 Neighboring gene RNA polymerase II, I and III subunit H Neighboring gene thrombopoietin

Go to nucleotide: Graphics FASTA GenBank

  • Project title: Tissue-specific circular RNA induction during human fetal development
  • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
  • BioProject: PRJNA270632
  • Publication: PMID 26076956
  • Analysis date: Mon Apr 2 22:54:59 2018

Related articles in PubMed

  1. Removal of gating in voltage-dependent ClC-2 chloride channel by point mutations affecting the pore and C-terminus CBS-2 domain. Yusef YR, et al. J Physiol, 2006 Apr 1. PMID 16469788, Free PMC Article
  2. Effect of CLC-2 on the cytoskeleton in human trabecular meshwork cells. Wang HW, et al. Mol Med Rep, 2013 Oct. PMID 23934342
  3. Brain white matter oedema due to ClC-2 chloride channel deficiency: an observational analytical study. Depienne C, et al. Lancet Neurol, 2013 Jul. PMID 23707145
  4. Analysis of CLCN2 as candidate gene for megalencephalic leukoencephalopathy with subcortical cysts. Scheper GC, et al. Genet Test Mol Biomarkers, 2010 Apr. PMID 20187760
  5. CryoEM structures of the human CLC-2 voltage-gated chloride channel reveal a ball-and-chain gating mechanism. Xu M, et al. Elife, 2024 Feb 12. PMID 38345841, Free PMC Article

See all (67) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Biallelic CLCN2 mutations cause retinal degeneration by impairing retinal pigment epithelium phagocytosis and chloride channel function.
    Title: Biallelic CLCN2 mutations cause retinal degeneration by impairing retinal pigment epithelium phagocytosis and chloride channel function.
  2. FHII is linked to the chromosome 7p22 region but also shows predicted heterogeneity.
    Title: Familial hyperaldosteronism type II is linked to the chromosome 7p22 region but also shows predicted heterogeneity.
  3. Functional Analysis and Clinical Significance of Chloride Channel 2 Expression in Esophageal Squamous Cell Carcinoma.
    Title: Functional Analysis and Clinical Significance of Chloride Channel 2 Expression in Esophageal Squamous Cell Carcinoma.
  4. Can Unlikely Neanderthal Chloride Channel CLC-2 Gene Variants Provide Insights in Modern Human Infertility?
    Title: Can Unlikely Neanderthal Chloride Channel CLC-2 Gene Variants Provide Insights in Modern Human Infertility?
  5. 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.
  6. 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.
  7. this study shows possible link between loss of ClC-2 function and an increased risk of developing atrial fibrillation
    Title: A Novel Loss-of-Function Variant in the Chloride Ion Channel Gene Clcn2 Associates with Atrial Fibrillation.
  8. Three de novo epilepsy-related gene missense mutations were identified in SCN1A, SCN8A and CLCN2 in childhood absence epilepsy patients.
    Title: De novo SCN1A, SCN8A, and CLCN2 mutations in childhood absence epilepsy.
  9. CLCN2 mutations cause primary aldosteronism, this highlight the importance of chloride in aldosterone biosynthesis and CLCN2 as the foremost chloride conductor of resting glomerulosa cells.
    Title: A gain-of-function mutation in the CLCN2 chloride channel gene causes primary aldosteronism.
  10. A role of anion channels in glomerulosa membrane potential determination, aldosterone production and hypertension. The mutations are the cause of a substantial fraction of early-onset primary aldosteronism.
    Title: CLCN2 chloride channel mutations in familial hyperaldosteronism type II.
Submit: New GeneRIF Correction See all GeneRIFs (50)

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables chloride channel activity IEA
Inferred from Electronic Annotation
more info
  
enables chloride channel regulator activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables chloride transmembrane transporter activity IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
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 TAS
Traceable Author Statement
more info
 PubMed 
enables voltage-gated monoatomic anion channel activity IEA
Inferred from Electronic Annotation
more info
  
enables volume-sensitive chloride channel activity IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
acts_upstream_of_or_within acinar cell differentiation IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within cell differentiation involved in salivary gland development IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular hypotonic response IEA
Inferred from Electronic Annotation
more info
  
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 IEA
Inferred from Electronic Annotation
more info
  
involved_in lung development IEA
Inferred from Electronic Annotation
more info
  
involved_in monoatomic anion transmembrane transport IEA
Inferred from Electronic Annotation
more info
  
involved_in monoatomic ion transmembrane transport IEA
Inferred from Electronic Annotation
more info
  
involved_in monoatomic ion transport IEA
Inferred from Electronic Annotation
more info
  
involved_in phagocytosis, engulfment IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of oligodendrocyte differentiation IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of aldosterone biosynthetic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of biological quality IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of membrane depolarization during action potential IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of resting membrane potential IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within retina development in camera-type eye IEA
Inferred from Electronic Annotation
more info
  
involved_in stabilization of membrane potential IEA
Inferred from Electronic Annotation
more info
  
involved_in transmembrane transport IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in astrocyte end-foot IDA
Inferred from Direct Assay
more info
 PubMed 
located_in astrocyte end-foot IEA
Inferred from Electronic Annotation
more info
  
located_in axon IEA
Inferred from Electronic Annotation
more info
  
located_in axon initial segment IEA
Inferred from Electronic Annotation
more info
  
located_in basolateral plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in basolateral plasma membrane IEA
Inferred from Electronic Annotation
more info
  
located_in cell projection IEA
Inferred from Electronic Annotation
more info
  
part_of chloride channel complex IEA
Inferred from Electronic Annotation
more info
  
located_in dendrite IEA
Inferred from Electronic Annotation
more info
  
located_in dendritic spine membrane IEA
Inferred from Electronic Annotation
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 myelin sheath IDA
Inferred from Direct Assay
more info
 PubMed 
located_in myelin sheath IEA
Inferred from Electronic Annotation
more info
  
located_in perikaryon 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 IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane IEA
Inferred from Electronic Annotation
more info
  
located_in plasma membrane TAS
Traceable Author Statement
more info
  
located_in postsynaptic membrane IEA
Inferred from Electronic Annotation
more info
  
located_in synapse IEA
Inferred from Electronic Annotation
more info
  
Preferred Names
chloride channel protein 2
Names
chloride channel 2
chloride channel, voltage-sensitive 2

NEW Try the new Transcript table

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

  1. NG_016422.1 RefSeqGene

    Range
    4999..20419
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001171087.3 → NP_001164558.1  chloride channel protein 2 isoform 2

    See identical proteins and their annotated locations for NP_001164558.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate in-frame splice junction at the 5' end of an exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.
    Source sequence(s)
    AA524434, BC072004, DC403930
    Consensus CDS
    CCDS54691.1
    UniProtKB/Swiss-Prot
    P51788
    Related
    ENSP00000345056.7, ENST00000344937.11
    Conserved Domains (3) summary
    cd03683
    Location:90 → 550
    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:773 → 821
    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:143 → 529
    Voltage_CLC; Voltage gated chloride channel

  2. NM_001171088.3 → NP_001164559.1  chloride channel protein 2 isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (3) has the same N- and C-termini but is shorter compared to isoform 1.
    Source sequence(s)
    AA524434, AC078797, AK302759, DC403930
    Consensus CDS
    CCDS54690.1
    UniProtKB/Swiss-Prot
    P51788
    Related
    ENSP00000400425.2, ENST00000434054.6
    Conserved Domains (3) summary
    cd03683
    Location:73 → 523
    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:746 → 794
    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:99 → 502
    Voltage_CLC; Voltage gated chloride channel

  3. NM_001171089.3 → NP_001164560.1  chloride channel protein 2 isoform 4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (4) has the same N- and C-termini but is shorter compared to isoform 1.
    Source sequence(s)
    AA524434, AC078797, AK298952, DC403930
    Consensus CDS
    CCDS54692.1
    UniProtKB/Swiss-Prot
    P51788
    Related
    ENSP00000391928.1, ENST00000457512.1
    Conserved Domains (2) summary
    cd03683
    Location:90 → 567
    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:143 → 546
    Voltage_CLC; Voltage gated chloride channel

  4. NM_004366.6 → NP_004357.3  chloride channel protein 2 isoform 1

    See identical proteins and their annotated locations for NP_004357.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AA524434, AC078797, AF026004, DC403930
    Consensus CDS
    CCDS3263.1
    UniProtKB/Swiss-Prot
    B4DQT9, B4DZ58, E9PBD9, E9PCD2, O14864, P51788, Q6IPA9, Q8WU13
    Related
    ENSP00000265593.4, ENST00000265593.9
    Conserved Domains (3) summary
    cd03683
    Location:90 → 567
    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:790 → 838
    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:143 → 546
    Voltage_CLC; Voltage gated chloride channel

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

    Range
    184346185..184361605 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006713489.2 → XP_006713552.1  chloride channel protein 2 isoform X1

    See identical proteins and their annotated locations for XP_006713552.1

    Conserved Domains (3) summary
    cd03683
    Location:90 → 567
    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:762 → 803
    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:143 → 546
    Voltage_CLC; Voltage gated chloride channel

  2. XM_011512401.2 → XP_011510703.1  chloride channel protein 2 isoform X2

    Conserved Domains (2) summary
    cd03683
    Location:90 → 567
    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:143 → 546
    Voltage_CLC; Voltage gated chloride channel

  3. XM_047447419.1 → XP_047303375.1  chloride channel protein 2 isoform X3

    UniProtKB/TrEMBL
    A0A1B0GUY6
    Related
    ENSP00000490313.1, ENST00000636492.1

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060927.1 Alternate T2T-CHM13v2.0

    Range
    187155451..187170873 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054345165.1 → XP_054201140.1  chloride channel protein 2 isoform X1

  2. XM_054345166.1 → XP_054201141.1  chloride channel protein 2 isoform X2

  3. XM_054345167.1 → XP_054201142.1  chloride channel protein 2 isoform X3

    UniProtKB/TrEMBL
    A0A1B0GUY6
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P51788.2 GenPept UniProtKB/Swiss-Prot:P51788

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

Chemical Information
Medical
Molecular Biology Databases
Research Materials
Tools
Miscellaneous