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

    Gene ID: 1182, updated on 10-Dec-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
    NEW
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    Try the new Transcript table

    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: 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

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    BioGRID CRISPR Screen Phenotypes (17 hits/1269 screens)

    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

    General gene information

    Clone Names

    • DKFZp564I0463

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding  
    enables PDZ domain binding PubMed 
    enables antiporter activity  
    enables chloride channel activity PubMed 
    enables chloride channel activity PubMed 
    enables protein binding PubMed 
    enables voltage-gated chloride channel activity  
    enables volume-sensitive chloride channel activity PubMed 
    Items 1 - 20 of 33
    Component Evidence Code Pubs
    is_active_in GABA-ergic synapse PubMed 
    is_active_in GABA-ergic synapse PubMed 
    is_active_in Golgi apparatus  
    located_in Golgi apparatus PubMed 
    located_in Golgi membrane  
    located_in axon terminus  
    located_in cell surface PubMed 
    located_in cytoplasmic vesicle PubMed 
    is_active_in early endosome  
    located_in early endosome PubMed 
    located_in early endosome membrane  
    located_in endosome membrane  
    located_in external side of plasma membrane PubMed 
    is_active_in glutamatergic synapse PubMed 
    is_active_in glutamatergic synapse PubMed 
    located_in intracellular membrane-bounded organelle  
    located_in late endosome PubMed 
    located_in late endosome membrane  
    located_in lysosomal membrane  
    located_in membrane PubMed 
    located_in membrane PubMed 
    located_in phagocytic vesicle PubMed 
    is_active_in plasma membrane  
    located_in plasma membrane PubMed 
    located_in recycling endosome  
    located_in ruffle membrane  
    located_in secretory granule PubMed 
    located_in specific granule PubMed 
    is_active_in synaptic vesicle  
    located_in synaptic vesicle PubMed 
    is_active_in synaptic vesicle membrane PubMed 
    is_active_in synaptic vesicle membrane PubMed 
    located_in vesicle membrane PubMed 
    Items 1 - 20 of 33

    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_001243372.2 → NP_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:136 → 615
      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:638 → 776
      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_001243374.2 → NP_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:109 → 615
      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:626 → 776
      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_001829.4 → NP_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:136 → 642
      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:653 → 803
      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_173872.4 → NP_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:136 → 642
      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:653 → 803
      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_047449584.1 → XP_047305540.1  H(+)/Cl(-) exchange transporter 3 isoform X3

      UniProtKB/TrEMBL
      B3KXK0
      Conserved Domains (2) summary
      cd03684
      Location:78 → 584
      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:595 → 745
      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_005262726.4 → XP_005262783.1  H(+)/Cl(-) exchange transporter 3 isoform X1

      UniProtKB/TrEMBL
      B3KXK0
      Conserved Domains (4) summary
      COG0517
      Location:629 → 774
      CBS; CBS domain [Signal transduction mechanisms]
      cd03684
      Location:109 → 615
      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:638 → 776
      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:194 → 595
      Voltage_CLC; Voltage gated chloride channel
    3. XM_047449586.1 → XP_047305542.1  H(+)/Cl(-) exchange transporter 3 isoform X4

      UniProtKB/TrEMBL
      B3KXK0
    4. XM_011531586.3 → XP_011529888.1  H(+)/Cl(-) exchange transporter 3 isoform X2

      UniProtKB/TrEMBL
      B3KXK0
      Conserved Domains (4) summary
      COG0517
      Location:621 → 766
      CBS; CBS domain [Signal transduction mechanisms]
      cd03684
      Location:101 → 607
      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:630 → 768
      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:186 → 587
      Voltage_CLC; Voltage gated chloride channel
    5. XM_047449585.1 → XP_047305541.1  H(+)/Cl(-) exchange transporter 3 isoform X4

      UniProtKB/TrEMBL
      B3KXK0

    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_054348875.1 → XP_054204850.1  H(+)/Cl(-) exchange transporter 3 isoform X5

      UniProtKB/TrEMBL
      B3KXK0
    2. XM_054348878.1 → XP_054204853.1  H(+)/Cl(-) exchange transporter 3 isoform X6

      UniProtKB/Swiss-Prot
      B7Z932, B9EGJ9, D3DP34, E9PB97, O14918, P51790, Q86Z21
      UniProtKB/TrEMBL
      B3KXK0
    3. XM_054348879.1 → XP_054204854.1  H(+)/Cl(-) exchange transporter 3 isoform X3

      UniProtKB/TrEMBL
      B3KXK0
    4. XM_054348876.1 → XP_054204851.1  H(+)/Cl(-) exchange transporter 3 isoform X1

      UniProtKB/TrEMBL
      B3KXK0
    5. XM_054348880.1 → XP_054204855.1  H(+)/Cl(-) exchange transporter 3 isoform X4

      UniProtKB/TrEMBL
      B3KXK0
    6. XM_054348877.1 → XP_054204852.1  H(+)/Cl(-) exchange transporter 3 isoform X2

      UniProtKB/TrEMBL
      B3KXK0
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