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

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: mouse all
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Genomic context

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_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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?
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.
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?
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.
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.
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.
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.
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

Associated conditions

Description	Tests
Dent disease type 1 MedGen: C1848336 OMIM: 300009 GeneReviews: Dent Disease	not available
Hypophosphatemic rickets, X-linked recessive MedGen: C1845168 OMIM: 300554 GeneReviews: Not available	not available
Proteinuria, low molecular weight, with hypercalciuria and nephrocalcinosis MedGen: C1839874 OMIM: 308990 GeneReviews: Not available	not available
X-linked recessive nephrolithiasis with renal failure MedGen: C0403720 OMIM: 310468 GeneReviews: Not available	not available

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 variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

WI-21198 (e-PCR)
- UniSTS:17470

STS-X81836 (e-PCR)
- UniSTS:60517

DXS8222 (e-PCR)
- UniSTS:34170

A007D27 (e-PCR)
- UniSTS:3226

DXS7647 (e-PCR)
- UniSTS:3007

DXS9840 (e-PCR)
- UniSTS:474056

stdJ519N18SP6 (e-PCR)
- UniSTS:181741

A007H45 (e-PCR)
- UniSTS:58106

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 more info	PubMed
located_in membrane	HDA more info	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

NG_007159.3 RefSeqGene

Range

4981..181615

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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 ...
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
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
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
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

NC_000023.11 Reference GRCh38.p14 Primary Assembly

Range

49922596..50099230

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
XM_047441808.1 → XP_047297764.1 H(+)/Cl(-) exchange transporter 5 isoform X2
XM_047441807.1 → XP_047297763.1 H(+)/Cl(-) exchange transporter 5 isoform X2