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CLCN3 chloride voltage-gated channel 3 [ Homo sapiens (human) ]

Gene ID: 1182, updated on 10-Oct-2024

Summary

Official Symbol
CLCN3provided by HGNC
Official Full Name
chloride voltage-gated channel 3provided by HGNC
Primary source
HGNC:HGNC:2021
See related
Ensembl:ENSG00000109572 MIM:600580; AllianceGenome:HGNC:2021
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
CLC3; ClC-3; NEDSBA; NEDHYBA
Summary
This gene encodes a member of the voltage-gated chloride channel (ClC) family. The encoded protein is present in all cell types and localized in plasma membranes and in intracellular vesicles. It is a multi-pass membrane protein which contains a ClC domain and two additional C-terminal CBS (cystathionine beta-synthase) domains. The ClC domain catalyzes the selective flow of Cl- ions across cell membranes, and the CBS domain may have a regulatory function. This protein plays a role in both acidification and transmitter loading of GABAergic synaptic vesicles, and in smooth muscle cell activation and neointima formation. This protein is required for lysophosphatidic acid (LPA)-activated Cl- current activity and fibroblast-to-myofibroblast differentiation. The protein activity is regulated by Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in glioma cells. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]
Expression
Ubiquitous expression in brain (RPKM 27.7), colon (RPKM 19.9) and 25 other tissues See more
Orthologs
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Genomic context

See CLCN3 in Genome Data Viewer
Location:
4q33
Exon count:
18
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (169620578..169723673)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (172980359..173083792)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (170541729..170644824)

Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105377529 Neighboring gene ReSE screen-validated silencer GRCh37_chr4:170211490-170211654 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22133 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22134 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:170232766-170233314 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:170256304-170256981 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22135 Neighboring gene ReSE screen-validated silencer GRCh37_chr4:170291383-170291609 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22136 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22137 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15793 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15794 Neighboring gene NIMA related kinase 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22138 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22139 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22140 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22141 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22142 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22143 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr4:170581329-170582201 Neighboring gene Sharpr-MPRA regulatory region 12659 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22145 Neighboring gene uncharacterized LOC107986240 Neighboring gene histone PARylation factor 1

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Neurodevelopmental disorder with hypotonia and brain abnormalities
MedGen: C5561977 OMIM: 619512 GeneReviews: Not available
not available
Neurodevelopmental disorder with seizures and brain abnormalities
MedGen: C5561979 OMIM: 619517 GeneReviews: Not available
not available

EBI GWAS Catalog

Description
Biological insights from 108 schizophrenia-associated genetic loci.
EBI GWAS Catalog

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Clone Names

  • DKFZp564I0463

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
 
enables PDZ domain binding IDA
Inferred from Direct Assay
more info
PubMed 
enables antiporter activity ISS
Inferred from Sequence or Structural Similarity
more info
 
enables chloride channel activity IDA
Inferred from Direct Assay
more info
PubMed 
enables chloride channel activity TAS
Traceable Author Statement
more info
PubMed 
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 volume-sensitive chloride channel activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
Component Evidence Code Pubs
is_active_in GABA-ergic synapse IDA
Inferred from Direct Assay
more info
PubMed 
is_active_in GABA-ergic synapse IMP
Inferred from Mutant Phenotype
more info
PubMed 
is_active_in Golgi apparatus IBA
Inferred from Biological aspect of Ancestor
more info
 
located_in Golgi apparatus IDA
Inferred from Direct Assay
more info
PubMed 
located_in Golgi membrane IEA
Inferred from Electronic Annotation
more info
 
located_in axon terminus IEA
Inferred from Electronic Annotation
more info
 
located_in cell surface NAS
Non-traceable Author Statement
more info
PubMed 
located_in cytoplasmic vesicle IDA
Inferred from Direct Assay
more info
PubMed 
is_active_in early endosome IBA
Inferred from Biological aspect of Ancestor
more info
 
located_in early endosome IDA
Inferred from Direct Assay
more info
PubMed 
located_in early endosome membrane IEA
Inferred from Electronic Annotation
more info
 
located_in endosome membrane ISS
Inferred from Sequence or Structural Similarity
more info
 
located_in external side of plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
is_active_in glutamatergic synapse IDA
Inferred from Direct Assay
more info
PubMed 
is_active_in glutamatergic synapse IMP
Inferred from Mutant Phenotype
more info
PubMed 
located_in intracellular membrane-bounded organelle IDA
Inferred from Direct Assay
more info
 
located_in late endosome IDA
Inferred from Direct Assay
more info
PubMed 
located_in late endosome membrane IEA
Inferred from Electronic Annotation
more info
 
located_in lysosomal membrane ISS
Inferred from Sequence or Structural Similarity
more info
 
located_in membrane HDA PubMed 
located_in membrane TAS
Traceable Author Statement
more info
PubMed 
located_in phagocytic vesicle 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 IDA
Inferred from Direct Assay
more info
PubMed 
located_in recycling endosome ISS
Inferred from Sequence or Structural Similarity
more info
 
located_in ruffle membrane IEA
Inferred from Electronic Annotation
more info
 
located_in secretory granule IDA
Inferred from Direct Assay
more info
PubMed 
located_in specific granule IDA
Inferred from Direct Assay
more info
PubMed 
is_active_in synaptic vesicle IBA
Inferred from Biological aspect of Ancestor
more info
 
located_in synaptic vesicle IDA
Inferred from Direct Assay
more info
PubMed 
is_active_in synaptic vesicle membrane IDA
Inferred from Direct Assay
more info
PubMed 
is_active_in synaptic vesicle membrane IMP
Inferred from Mutant Phenotype
more info
PubMed 
located_in vesicle membrane IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

Preferred Names
H(+)/Cl(-) exchange transporter 3
Names
chloride channel 3
chloride channel protein 3
chloride channel, voltage-sensitive 3
chloride transporter ClC-3

NCBI Reference Sequences (RefSeq)

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_029731.2 RefSeqGene

    Range
    5002..108097
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001243372.2NP_001230301.1  H(+)/Cl(-) exchange transporter 3 isoform a

    See identical proteins and their annotated locations for NP_001230301.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (a) lacks an in-frame exon in the middle coding region, compared to variant b. The resulting isoform (a) lacks an internal segment, compared to isoform b.
    Source sequence(s)
    AA780395, AC106878, AK304362, DA102505
    Consensus CDS
    CCDS58932.1
    UniProtKB/TrEMBL
    B3KXK0
    Related
    ENSP00000353857.3, ENST00000360642.7
    Conserved Domains (2) summary
    cd03684
    Location:136615
    ClC_3_like; ClC-3-like chloride channel proteins. This CD includes ClC-3, ClC-4, ClC-5 and ClC-Y1. ClC-3 was initially cloned from rat kidney. Expression of ClC-3 produces outwardly-rectifying Cl currents that are inhibited by protein kinase C activation. It has ...
    cd04591
    Location:638776
    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 ...
  2. NM_001243374.2NP_001230303.2  H(+)/Cl(-) exchange transporter 3 isoform c

    Status: REVIEWED

    Description
    Transcript Variant: This variant (c) lacks two exons from the 5' end but has an alternate 5' exon, compared to variant b. The resulting isoform (c) has a shorter and distinct N-terminus, compared to isoform b.
    Source sequence(s)
    AC106878
    Consensus CDS
    CCDS75208.1
    UniProtKB/TrEMBL
    A0A087WU31, B3KXK0, E9PE15
    Related
    ENSP00000425323.2, ENST00000507875.6
    Conserved Domains (2) summary
    cd03684
    Location:109615
    ClC_3_like; ClC-3-like chloride channel proteins. This CD includes ClC-3, ClC-4, ClC-5 and ClC-Y1. ClC-3 was initially cloned from rat kidney. Expression of ClC-3 produces outwardly-rectifying Cl currents that are inhibited by protein kinase C activation. It has ...
    cd04591
    Location:626776
    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
  3. NM_001829.4NP_001820.2  H(+)/Cl(-) exchange transporter 3 isoform b

    See identical proteins and their annotated locations for NP_001820.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (b) represents the predominant transcript and encodes isoform b.
    Source sequence(s)
    AA780395, AC106878, BC136510, BX647119
    Consensus CDS
    CCDS34101.1
    UniProtKB/Swiss-Prot
    B7Z932, B9EGJ9, D3DP34, E9PB97, O14918, P51790, Q86Z21
    UniProtKB/TrEMBL
    B3KXK0
    Related
    ENSP00000424603.1, ENST00000513761.6
    Conserved Domains (2) summary
    cd03684
    Location:136642
    ClC_3_like; ClC-3-like chloride channel proteins. This CD includes ClC-3, ClC-4, ClC-5 and ClC-Y1. ClC-3 was initially cloned from rat kidney. Expression of ClC-3 produces outwardly-rectifying Cl currents that are inhibited by protein kinase C activation. It has ...
    cd04591
    Location:653803
    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
  4. NM_173872.4NP_776297.2  H(+)/Cl(-) exchange transporter 3 isoform e

    See identical proteins and their annotated locations for NP_776297.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (e) has an additional exon in the 3' coding region, which results in frame-shift, compared to variant b. The resulting isoform (e) has a longer and distinct C-terminus, compared to isoform b.
    Source sequence(s)
    AA780395, AB019542, AC106878, AK304362, DA102505
    Consensus CDS
    CCDS34100.1
    UniProtKB/TrEMBL
    B3KXK0
    Related
    ENSP00000261514.5, ENST00000347613.9
    Conserved Domains (2) summary
    cd03684
    Location:136642
    ClC_3_like; ClC-3-like chloride channel proteins. This CD includes ClC-3, ClC-4, ClC-5 and ClC-Y1. ClC-3 was initially cloned from rat kidney. Expression of ClC-3 produces outwardly-rectifying Cl currents that are inhibited by protein kinase C activation. It has ...
    cd04591
    Location:653803
    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

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_000004.12 Reference GRCh38.p14 Primary Assembly

    Range
    169620578..169723673
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047449584.1XP_047305540.1  H(+)/Cl(-) exchange transporter 3 isoform X3

    Conserved Domains (2) summary
    cd03684
    Location:78584
    ClC_3_like; ClC-3-like chloride channel proteins. This CD includes ClC-3, ClC-4, ClC-5 and ClC-Y1. ClC-3 was initially cloned from rat kidney. Expression of ClC-3 produces outwardly-rectifying Cl currents that are inhibited by protein kinase C activation. It has ...
    cd04591
    Location:595745
    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
  2. XM_005262726.4XP_005262783.1  H(+)/Cl(-) exchange transporter 3 isoform X1

    UniProtKB/TrEMBL
    B3KXK0
    Conserved Domains (4) summary
    COG0517
    Location:629774
    CBS; CBS domain [Signal transduction mechanisms]
    cd03684
    Location:109615
    ClC_3_like; ClC-3-like chloride channel proteins. This CD includes ClC-3, ClC-4, ClC-5 and ClC-Y1. ClC-3 was initially cloned from rat kidney. Expression of ClC-3 produces outwardly-rectifying Cl currents that are inhibited by protein kinase C activation. It has ...
    cd04591
    Location:638776
    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:194595
    Voltage_CLC; Voltage gated chloride channel
  3. XM_047449586.1XP_047305542.1  H(+)/Cl(-) exchange transporter 3 isoform X4

  4. XM_011531586.3XP_011529888.1  H(+)/Cl(-) exchange transporter 3 isoform X2

    UniProtKB/TrEMBL
    B3KXK0
    Conserved Domains (4) summary
    COG0517
    Location:621766
    CBS; CBS domain [Signal transduction mechanisms]
    cd03684
    Location:101607
    ClC_3_like; ClC-3-like chloride channel proteins. This CD includes ClC-3, ClC-4, ClC-5 and ClC-Y1. ClC-3 was initially cloned from rat kidney. Expression of ClC-3 produces outwardly-rectifying Cl currents that are inhibited by protein kinase C activation. It has ...
    cd04591
    Location:630768
    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:186587
    Voltage_CLC; Voltage gated chloride channel
  5. XM_047449585.1XP_047305541.1  H(+)/Cl(-) exchange transporter 3 isoform X4

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060928.1 Alternate T2T-CHM13v2.0

    Range
    172980359..173083792
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054348875.1XP_054204850.1  H(+)/Cl(-) exchange transporter 3 isoform X5

  2. XM_054348878.1XP_054204853.1  H(+)/Cl(-) exchange transporter 3 isoform X6

    UniProtKB/Swiss-Prot
    B7Z932, B9EGJ9, D3DP34, E9PB97, O14918, P51790, Q86Z21
  3. XM_054348879.1XP_054204854.1  H(+)/Cl(-) exchange transporter 3 isoform X3

  4. XM_054348876.1XP_054204851.1  H(+)/Cl(-) exchange transporter 3 isoform X1

  5. XM_054348880.1XP_054204855.1  H(+)/Cl(-) exchange transporter 3 isoform X4

  6. XM_054348877.1XP_054204852.1  H(+)/Cl(-) exchange transporter 3 isoform X2