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    CLCN5 chloride voltage-gated channel 5 [ Homo sapiens (human) ]

    Gene ID: 1184, updated on 17-Dec-2023

    Summary

    Official Symbol
    CLCN5provided by HGNC
    Official Full Name
    chloride voltage-gated channel 5provided by HGNC
    Primary source
    HGNC:HGNC:2023
    See related
    Ensembl:ENSG00000171365 MIM:300008; AllianceGenome:HGNC:2023
    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
    XRN; CLC5; XLRH; CLCK2; ClC-5; DENT1; DENTS; NPHL1; NPHL2; hCIC-K2
    Summary
    This gene encodes a member of the ClC family of chloride ion channels and ion transporters. The encoded protein is primarily localized to endosomal membranes and may function to facilitate albumin uptake by the renal proximal tubule. Mutations in this gene have been found in Dent disease and renal tubular disorders complicated by nephrolithiasis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2013]
    Expression
    Biased expression in kidney (RPKM 20.4), liver (RPKM 3.6) and 13 other tissues See more
    Orthologs
    NEW
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    Try the new Transcript table

    Genomic context

    See CLCN5 in Genome Data Viewer
    Location:
    Xp11.23
    Exon count:
    18
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (49922596..50099230)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (49238534..49416892)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (49687206..49863887)

    Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20846 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20847 Neighboring gene ubiquitin specific peptidase 27 X-linked Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20848 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20849 Neighboring gene CPSF1 pseudogene 2 Neighboring gene RNA, U6 small nuclear 421, pseudogene Neighboring gene microRNA 532 Neighboring gene microRNA 500a Neighboring gene microRNA 188 Neighboring gene microRNA 500b Neighboring gene microRNA 362 Neighboring gene microRNA 501 Neighboring gene microRNA 660 Neighboring gene microRNA 502 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chrX:49809130-49809715 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chrX:49854497-49855696 Neighboring gene peptide YY 3 (pseudogene) Neighboring gene A-kinase anchoring protein 4

    Genomic regions, transcripts, and products

    Expression

    • Project title: 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

    Phenotypes

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated 2012-10-18)

    ClinGen Genome Curation Page
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated 2012-10-18)

    ClinGen Genome Curation PagePubMed

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Clone Names

    • FLJ11432

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables antiporter activity TAS
    Traceable Author Statement
    more info
     
    enables identical protein binding IPI
    Inferred from Physical Interaction
    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 voltage-gated chloride channel activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    Process Evidence Code Pubs
    involved_in chloride transmembrane transport IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in chloride transport IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in endocytosis IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in monoatomic ion transmembrane transport TAS
    Traceable Author Statement
    more info
     
    involved_in renal system process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    Component Evidence Code Pubs
    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
     
    located_in Golgi membrane IEA
    Inferred from Electronic Annotation
    more info
     
    located_in apical part of cell IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
     
    is_active_in early endosome IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in endosome membrane TAS
    Traceable Author Statement
    more info
     
    located_in lysosomal membrane HDA PubMed 
    located_in membrane HDA PubMed 
    located_in membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
     
    is_active_in synaptic vesicle IBA
    Inferred from Biological aspect of Ancestor
    more info
     

    General protein information

    Preferred Names
    H(+)/Cl(-) exchange transporter 5
    Names
    chloride channel, voltage-sensitive 5
    chloride transporter ClC-5
    voltage-gated chloride ion channel CLCN5

    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_007159.3 RefSeqGene

      Range
      4981..181615
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000084.5NP_000075.1  H(+)/Cl(-) exchange transporter 5 isoform b

      See identical proteins and their annotated locations for NP_000075.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3, also known as type 3) lacks several 5' exons but has an alternate 5' exon, and it thus differs in the 5' UTR and uses a downstream start codon, compared to variant 1. The resulting isoform (b) has a shorter N-terminus, compared to isoform a.
      Source sequence(s)
      AC231645, AK025562, AK290940, BC051691, BX950885
      Consensus CDS
      CCDS14328.1
      UniProtKB/TrEMBL
      A8K4H5
      Related
      ENSP00000365276.3, ENST00000376108.7
      Conserved Domains (2) summary
      cd03684
      Location:72570
      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:595731
      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_001127898.4NP_001121370.1  H(+)/Cl(-) exchange transporter 5 isoform a

      See identical proteins and their annotated locations for NP_001121370.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2, also known as type 1) uses an alternate splice site in the 5' UTR, compared to variant 1. Both variants 1 and 2 encode the same isoform (a).
      Source sequence(s)
      AC231645, AC236430, AK025562, AK056560, BC051691, DA652242
      Consensus CDS
      CCDS48115.1
      UniProtKB/Swiss-Prot
      A1L475, B3KPN6, P51795, Q5JQD5, Q7RTN8
      UniProtKB/TrEMBL
      A8K4H5
      Related
      ENSP00000365259.3, ENST00000376091.8
      Conserved Domains (2) summary
      cd03684
      Location:142640
      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:651801
      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_001127899.4NP_001121371.1  H(+)/Cl(-) exchange transporter 5 isoform a

      See identical proteins and their annotated locations for NP_001121371.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1, also known as type 2) represents the longest transcript and encodes the longest isoform (a). Both variants 1 and 2 encode the same isoform.
      Source sequence(s)
      AC231645, AC236430, AK025562, AK092049, BC051691, BK000969, DA737534
      Consensus CDS
      CCDS48115.1
      UniProtKB/Swiss-Prot
      A1L475, B3KPN6, P51795, Q5JQD5, Q7RTN8
      UniProtKB/TrEMBL
      A8K4H5
      Related
      ENSP00000365256.3, ENST00000376088.7
      Conserved Domains (2) summary
      cd03684
      Location:142640
      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:651801
      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_001272102.2NP_001259031.1  H(+)/Cl(-) exchange transporter 5 isoform c

      See identical proteins and their annotated locations for NP_001259031.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) uses an alternate splice site in the 5' UTR, it lacks several 3' exons but has an alternate 3' terminal exon, and it thus differs in the 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (c) has a distinct and shorter C-terminus, compared to isoform a.
      Source sequence(s)
      AC236430, AK092049, BF513571
      Consensus CDS
      CCDS69763.1
      UniProtKB/TrEMBL
      V9GYG7
      Related
      ENSP00000476732.1, ENST00000482218.2
    5. NM_001282163.2NP_001269092.1  H(+)/Cl(-) exchange transporter 5 isoform d

      See identical proteins and their annotated locations for NP_001269092.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4, also known as type 4) lacks several 5' exons but has an alternate 5' exon, and it thus differs in the 5' UTR and uses an alternate start codon, compared to variant 1. The resulting isoform (d) has a shorter and distinct N-terminus, compared to isoform a.
      Source sequence(s)
      AC231645, AK025562, BC051691, X91906
      UniProtKB/TrEMBL
      A8K4H5
      Conserved Domains (4) summary
      COG0517
      Location:603749
      CBS; CBS domain [Signal transduction mechanisms]
      cd03684
      Location:92590
      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:615751
      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:169570
      Voltage_CLC; Voltage gated chloride channel

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000023.11 Reference GRCh38.p14 Primary Assembly

      Range
      49922596..50099230
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017029258.2XP_016884747.1  H(+)/Cl(-) exchange transporter 5 isoform X1

      UniProtKB/TrEMBL
      A8K4H5
      Conserved Domains (2) summary
      cd03684
      Location:146644
      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:655805
      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_017029257.2XP_016884746.1  H(+)/Cl(-) exchange transporter 5 isoform X1

      UniProtKB/TrEMBL
      A8K4H5
      Conserved Domains (2) summary
      cd03684
      Location:146644
      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:655805
      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. XM_047441808.1XP_047297764.1  H(+)/Cl(-) exchange transporter 5 isoform X2

      UniProtKB/TrEMBL
      A8K4H5
    4. XM_047441807.1XP_047297763.1  H(+)/Cl(-) exchange transporter 5 isoform X2

      UniProtKB/TrEMBL
      A8K4H5

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060947.1 Alternate T2T-CHM13v2.0

      Range
      49238534..49416892
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054326432.1XP_054182407.1  H(+)/Cl(-) exchange transporter 5 isoform X1

      UniProtKB/TrEMBL
      A8K4H5
    2. XM_054326433.1XP_054182408.1  H(+)/Cl(-) exchange transporter 5 isoform X1

      UniProtKB/TrEMBL
      A8K4H5
    3. XM_054326434.1XP_054182409.1  H(+)/Cl(-) exchange transporter 5 isoform X2

      UniProtKB/TrEMBL
      A8K4H5