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

Gene ID: 1184, updated on 27-Nov-2024

Summary

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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
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Genomic context

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See CLCN5 in Genome Data Viewer
Location:
Xp11.23
Exon count:
18
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (49922596..50099230)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (49238534..49416892)
RS_2024_09 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

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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

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Related articles in PubMed

  1. Novel mutations of the CLCN5 gene including a complex allele and A 5' UTR mutation in Dent disease 1. Tosetto E, et al. Clin Genet, 2009 Oct. PMID 19673950
  2. Nucleotides bind to the C-terminus of ClC-5. Wellhauser L, et al. Biochem J, 2006 Sep 1. PMID 16686597, Free PMC Article
  3. Hypercalciuria in patients with CLCN5 mutations. Ludwig M, et al. Pediatr Nephrol, 2006 Sep. PMID 16807762
  4. Phenotypic and genetic heterogeneity in Dent's disease--the results of an Italian collaborative study. Tosetto E, et al. Nephrol Dial Transplant, 2006 Sep. PMID 16822791
  5. A missense mutation in the chloride/proton ClC-5 antiporter gene results in increased expression of an alternative mRNA form that lacks exons 10 and 11. Identification of seven new CLCN5 mutations in patients with Dent's disease. Ramos-Trujillo E, et al. J Hum Genet, 2007. PMID 17262170

See all (113) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Clinical features and genetic analysis of 15 Chinese children with dent disease.
    Title: Clinical features and genetic analysis of 15 Chinese children with dent disease.
  2. Dent disease 1-linked novel CLCN5 mutations result in aberrant location and reduced ion currents.
    Title: Dent disease 1-linked novel CLCN5 mutations result in aberrant location and reduced ion currents.
  3. Human parietal epithelial cells (PECs) and proteinuria in lupus nephritis: a role for ClC-5, megalin, and cubilin?
    Title: Human parietal epithelial cells (PECs) and proteinuria in lupus nephritis: a role for ClC-5, megalin, and cubilin?
  4. A Study on the CLCN5 Gene in Iranian Patients: A Report of Novel and Recurrent Mutations.
    Title: A Study on the CLCN5 Gene in Iranian Patients: A Report of Novel and Recurrent Mutations.
  5. Emerging Perspectives on the Rare Tubulopathy Dent Disease: Is Glomerular Damage a Direct Consequence of ClC-5 Dysfunction?
    Title: Emerging Perspectives on the Rare Tubulopathy Dent Disease: Is Glomerular Damage a Direct Consequence of ClC-5 Dysfunction?
  6. CLCN5 5'UTR isoforms in human kidneys: differential expression analysis between controls and patients with glomerulonephritis.
    Title: CLCN5 5'UTR isoforms in human kidneys: differential expression analysis between controls and patients with glomerulonephritis.
  7. Prevalence of low molecular weight proteinuria and Dent disease 1 CLCN5 mutations in proteinuric cohorts.
    Title: Prevalence of low molecular weight proteinuria and Dent disease 1 CLCN5 mutations in proteinuric cohorts.
  8. Functional analysis of suspected splicing variants in CLCN5 gene in Dent disease 1.
    Title: Functional analysis of suspected splicing variants in CLCN5 gene in Dent disease 1.
  9. Phenotypic spectrum and antialbuminuric response to angiotensin converting enzyme inhibitor and angiotensin receptor blocker therapy in pediatric Dent disease.
    Title: Phenotypic spectrum and antialbuminuric response to angiotensin converting enzyme inhibitor and angiotensin receptor blocker therapy in pediatric Dent disease.
  10. Multicenter study of the clinical features and mutation gene spectrum of Chinese children with Dent disease.
    Title: Multicenter study of the clinical features and mutation gene spectrum of Chinese children with Dent disease.
Submit: New GeneRIF Correction See all GeneRIFs (72)

Phenotypes

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

Review eQTL and phenotype association data in this region using PheGenI

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

Variation

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See Variation Viewer (GRCh37.p13)

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

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 
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
  
is_active_in synaptic vesicle IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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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)

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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.

Genomic

  1. NG_007159.3 RefSeqGene

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

mRNA and Protein(s)

  1. NM_000084.5 → NP_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:72 → 570
    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 → 731
    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_001127898.4 → NP_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:142 → 640
    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:651 → 801
    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_001127899.4 → NP_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:142 → 640
    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:651 → 801
    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_001272102.2 → NP_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_001282163.2 → NP_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:603 → 749
    CBS; CBS domain [Signal transduction mechanisms]
    cd03684
    Location:92 → 590
    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:615 → 751
    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:169 → 570
    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_000023.11 Reference GRCh38.p14 Primary Assembly

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

mRNA and Protein(s)

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

    UniProtKB/TrEMBL
    A8K4H5
    Conserved Domains (2) summary
    cd03684
    Location:146 → 644
    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:655 → 805
    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_017029257.2 → XP_016884746.1  H(+)/Cl(-) exchange transporter 5 isoform X1

    UniProtKB/TrEMBL
    A8K4H5
    Conserved Domains (2) summary
    cd03684
    Location:146 → 644
    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:655 → 805
    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_047441808.1 → XP_047297764.1  H(+)/Cl(-) exchange transporter 5 isoform X2

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

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_054326432.1 → XP_054182407.1  H(+)/Cl(-) exchange transporter 5 isoform X1

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

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

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P51795.2 GenPept UniProtKB/Swiss-Prot:P51795

Gene LinkOut

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