Clcn5 chloride channel, voltage-sensitive 5 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Clcn5provided by MGI
Official Full Name: chloride channel, voltage-sensitive 5provided by MGI
Primary source: MGI:MGI:99486
See related: Ensembl:ENSMUSG00000004317 AllianceGenome:MGI:99486
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Clc5; ClC-5; Sfc13; Clc4-1; Clcn4-1; DXImx42e; 5430408K11Rik; D930009B12Rik
Summary: Predicted to enable identical protein binding activity and voltage-gated chloride channel activity. Acts upstream of or within endocytosis. Located in apical part of cell and endosome. Is expressed in several structures, including early conceptus; heart; metanephros; oocyte; and stomach. Used to study Dent disease. Human ortholog(s) of this gene implicated in Dent disease 1; X-linked nephrolithiasis type I; X-linked recessive hypophosphatemic rickets; and low molecular weight proteinuria with hypercalciuric nephrocalcinosis. Orthologous to human CLCN5 (chloride voltage-gated channel 5). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Broad expression in limb E14.5 (RPKM 8.4), placenta adult (RPKM 7.7) and 26 other tissues See more
Orthologs: human all
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Genomic context

Location:: X A1.1; X 3.21 cM

Exon count:: 20

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	X	NC_000086.8 (7020049..7185597, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	X	NC_000086.7 (7153810..7319358, complement)

Chromosome X - NC_000086.8 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Identification of an Electrogenic 2Cl[-]/H[+] Exchanger, ClC5, as a Chloride-Secreting Transporter Candidate in Kidney Cyst Epithelium in Tuberous Sclerosis.
Title: Identification of an Electrogenic 2Cl(-)/H(+) Exchanger, ClC5, as a Chloride-Secreting Transporter Candidate in Kidney Cyst Epithelium in Tuberous Sclerosis.
This study demonistrated that Clcn5 gene expression in mouse dorsal raphe nucleus
Title: Patterned expression of ion channel genes in mouse dorsal raphe nucleus determined with the Allen Mouse Brain Atlas.
ClC-5 plays an essential role in exocytosis of NHE3.
Title: Chloride channel (Clc)-5 is necessary for exocytic trafficking of Na+/H+ exchanger 3 (NHE3).
HNF1alpha directly regulates the expression of ClC-5 in the renal proximal tubule
Title: The transcription factor HNF1α regulates expression of chloride-proton exchanger ClC-5 in the renal proximal tubule.
ClC-5 is unique among CLC proteins in being crucial for proximal tubular endocytosis and the PY-motif-dependent ubiquitylation of ClC-5 is dispensable for this rol
Title: Role of ClC-5 in renal endocytosis is unique among ClC exchangers and does not require PY-motif-dependent ubiquitylation.
findings show that endosomal chloride concentration, which is raised by ClC-5 in exchange for protons accumulated by H+-ATPase, may play a role in endocytosis
Title: Endosomal chloride-proton exchange rather than chloride conductance is crucial for renal endocytosis.
Our studies demonstrate a role for CLC-5 in the immunopathogenesis of ulcerative colitis
Title: Clcn5 knockout mice exhibit novel immunomodulatory effects and are more susceptible to dextran sulfate sodium-induced colitis.
ClC-5 regulates dentin development through TGF-beta1 pathway
Title: ClC-5 regulates dentin development through TGF-beta1 pathway.
in the thyroid, unlike in the kidney, ClC-5 does not affect megalin expression and function
Title: ClC-5 does not affect megalin expression and function in the thyroid.
lack of proximal tubule cLCN5 in mice and men is associated with CAIII induction, increased cell proliferation, and oxidative stress
Title: A novel renal carbonic anhydrase type III plays a role in proximal tubule dysfunction.

Submit: New GeneRIF Correction See all GeneRIFs (22)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (3) 1 citation
Targeted (8) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH125271 (e-PCR)
- UniSTS:162093

DXImx35 (e-PCR), detects polymorphism
- UniSTS:186219

DXImx36 (e-PCR), detects polymorphism
- UniSTS:186220

DXImx5 (e-PCR), detects polymorphism
- UniSTS:181869

Clcn5 (e-PCR), detects polymorphism
- UniSTS:545916

px-59e4 (e-PCR)
- UniSTS:257986

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables antiporter activity	IEA Inferred from Electronic Annotation more info
enables chloride channel activity	ISO Inferred from Sequence Orthology more info
enables identical protein binding	IEA Inferred from Electronic Annotation more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables voltage-gated chloride channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables voltage-gated chloride channel activity	IEA Inferred from Electronic Annotation more info
enables voltage-gated chloride channel activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in chloride transmembrane transport	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within chloride transport	ISO Inferred from Sequence Orthology more info
involved_in chloride transport	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within endocytosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in renal system process	IEA Inferred from Electronic Annotation more info
involved_in renal system process	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
is_active_in Golgi apparatus	IBA Inferred from Biological aspect of Ancestor more info
located_in Golgi apparatus	ISO Inferred from Sequence Orthology 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 apical part of cell	ISO Inferred from Sequence Orthology more info
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
is_active_in early endosome	IBA Inferred from Biological aspect of Ancestor more info
located_in endosome	IDA Inferred from Direct Assay more info	PubMed
located_in endosome	ISO Inferred from Sequence Orthology more info
located_in endosome membrane	IEA Inferred from Electronic Annotation more info
located_in membrane	ISO Inferred from Sequence Orthology more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	ISO Inferred from Sequence Orthology 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 4-1; chloride channel 5; chloride channel protein 5; chloride transporter ClC-5

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.

mRNA and Protein(s)

NM_001243762.1 → NP_001230691.1 H(+)/Cl(-) exchange transporter 5 isoform 2

Status: VALIDATED

Description

Transcript Variant: This variant (2) includes two alternate exons in the 5' UTR and 5' CDS, compared to variant 1. It encodes isoform 2, which is longer and has a distinct N-terminus, compared to isoform 1.

Source sequence(s)

AL663104, AL808124

Consensus CDS

CCDS57727.1

UniProtKB/Swiss-Prot

B1ATV0, B1AXN0, Q9WVD4

UniProtKB/TrEMBL

Q3UL16

Related

ENSMUSP00000111412.2, ENSMUST00000115746.8

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_016691.4 → NP_057900.3 H(+)/Cl(-) exchange transporter 5 isoform 1

See identical proteins and their annotated locations for NP_057900.3

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the shorter transcript and encodes the shorter isoform (1).

Source sequence(s)

AF134117, AK052990, AK145763, AL808124

Consensus CDS

CCDS29963.1

UniProtKB/TrEMBL

Q3UL16

Related

ENSMUSP00000004428.8, ENSMUST00000004428.14

Conserved Domains (4) summary

COG0517
Location:583 → 729

CBS; CBS domain [Signal transduction mechanisms]

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 ...

pfam00654
Location:149 → 550

Voltage_CLC; Voltage gated chloride channel

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000086.8 Reference GRCm39 C57BL/6J

Range

7020049..7185597 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006527562.5 → XP_006527625.1 H(+)/Cl(-) exchange transporter 5 isoform X3

UniProtKB/TrEMBL

Q3UL16

Conserved Domains (2) summary

cd03684
Location:154 → 652

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:663 → 813

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_011247445.4 → XP_011245747.1 H(+)/Cl(-) exchange transporter 5 isoform X2

UniProtKB/TrEMBL

Q3UL16

Conserved Domains (2) summary

cd03684
Location:165 → 663

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:674 → 824

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_011247442.3 → XP_011245744.1 H(+)/Cl(-) exchange transporter 5 isoform X1

See identical proteins and their annotated locations for XP_011245744.1

UniProtKB/TrEMBL

Q3UL16

Conserved Domains (2) summary

cd03684
Location:177 → 675

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:686 → 836

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_011247443.4 → XP_011245745.1 H(+)/Cl(-) exchange transporter 5 isoform X1

See identical proteins and their annotated locations for XP_011245745.1

UniProtKB/TrEMBL

Q3UL16

Conserved Domains (2) summary

cd03684
Location:177 → 675

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:686 → 836

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_011247444.4 → XP_011245746.1 H(+)/Cl(-) exchange transporter 5 isoform X1

See identical proteins and their annotated locations for XP_011245746.1

UniProtKB/TrEMBL

Q3UL16

Conserved Domains (2) summary

cd03684
Location:177 → 675

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:686 → 836

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_036161803.1 → XP_036017696.1 H(+)/Cl(-) exchange transporter 5 isoform X4

UniProtKB/Swiss-Prot

B1ATV0, B1AXN0, Q9WVD4

UniProtKB/TrEMBL

Q3UL16

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
XM_011247446.4 → XP_011245748.1 H(+)/Cl(-) exchange transporter 5 isoform X5

UniProtKB/TrEMBL

Q3UL16

Conserved Domains (2) summary

cd03684
Location:138 → 636

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:647 → 797

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