Clcn3 chloride channel, voltage-sensitive 3 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Clcn3provided by MGI
Official Full Name: chloride channel, voltage-sensitive 3provided by MGI
Primary source: MGI:MGI:103555
See related: Ensembl:ENSMUSG00000004319 AllianceGenome:MGI:103555
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: Clc3
Summary: Enables antiporter activity. Involved in synaptic vesicle lumen acidification. Acts upstream of or within several processes, including chemical synaptic transmission; photoreceptor cell maintenance; and positive regulation of reactive oxygen species biosynthetic process. Located in several cellular components, including endosome membrane; lysosomal membrane; and synaptic vesicle. Is active in glutamatergic synapse. Is expressed in several structures, including central nervous system; dorsal root ganglion; early conceptus; genitourinary system; and heart. Used to study neuronal ceroid lipofuscinosis 3. Orthologous to human CLCN3 (chloride voltage-gated channel 3). [provided by Alliance of Genome Resources, Nov 2024]
Expression: Ubiquitous expression in cerebellum adult (RPKM 11.4), frontal lobe adult (RPKM 10.6) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 8 B3.1; 8 30.9 cM

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	8	NC_000074.7 (61363423..61436351, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	8	NC_000074.6 (60910389..60983317, complement)

Chromosome 8 - NC_000074.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data 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?

De novo CLCN3 variants affecting Gly327 cause severe neurodevelopmental syndrome with brain structural abnormalities.
Title: De novo CLCN3 variants affecting Gly327 cause severe neurodevelopmental syndrome with brain structural abnormalities.
Knockdown of CLC-3 may improve cognitive impairment caused by diabetic encephalopathy.
Title: Knockdown of CLC-3 may improve cognitive impairment caused by diabetic encephalopathy.
Excess iodide-induced reactive oxygen species elicit iodide efflux via beta-tubulin-associated ClC-3 in thyrocytes.
Title: Excess iodide-induced reactive oxygen species elicit iodide efflux via β-tubulin-associated ClC-3 in thyrocytes.
Angiotensin-(1-7) ameliorates high glucose-induced vascular endothelial injury through suppressing chloride channel 3.
Title: Angiotensin-(1-7) ameliorates high glucose-induced vascular endothelial injury through suppressing chloride channel 3.
The role of voltage-gated chloride channels in the epileptogenesis of temporal lobe epilepsy.
Title: The role of voltage-gated chloride channels in the epileptogenesis of temporal lobe epilepsy.
Unique variants in CLCN3, encoding an endosomal anion/proton exchanger, underlie a spectrum of neurodevelopmental disorders.
Title: Unique variants in CLCN3, encoding an endosomal anion/proton exchanger, underlie a spectrum of neurodevelopmental disorders.
Uncoupling endosomal CLC chloride/proton exchange causes severe neurodegeneration.
Title: Uncoupling endosomal CLC chloride/proton exchange causes severe neurodegeneration.
ClC-3 plays a critical role in the angiogenic capacity of EPCs and EPC-mediated neovascularization of ischemic tissues. Disturbance of CXCR4/JAK-2 signalling may contribute to the functional impairment of ClC-3 deficient EPCs. Thus, ClC-3 may be a potential therapeutic target for modulating neovascularization in ischemic diseases.
Title: ClC-3 Deficiency Impairs the Neovascularization Capacity of Early Endothelial Progenitor Cells by Decreasing CXCR4/JAK-2 Signalling.
intracellular Cl(-) regulation by ANO1/ClC-3 participates in HER2 transcription, mediating the PI3K/AKT/mTOR and/or STAT3 signaling pathway(s) in HER2-positive breast cancer cells.
Title: Transcriptional repression of human epidermal growth factor receptor 2 by ClC-3 Cl(-) /H(+) transporter inhibition in human breast cancer cells.
Abrogating ClC-3 blunts lipopolysaccharide-induced Inflammation via blocking the TLR4/NF-kappaB pathway.
Title: Abrogating ClC-3 Inhibits LPS-induced Inflammation via Blocking the TLR4/NF-κB Pathway.

Submit: New GeneRIF Correction See all GeneRIFs (51)

Variation

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Alleles

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

Endonuclease-mediated (2)
Gene trapped (1)
Targeted (9) 1 citation

General gene information

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Markers

RH129711 (e-PCR)
- UniSTS:213006

Clcn3 (e-PCR), detects polymorphism
- UniSTS:141347

Clcn3 (e-PCR), detects polymorphism
- UniSTS:141348

D1S3690 (e-PCR)
- UniSTS:474268

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables PDZ domain binding	ISO Inferred from Sequence Orthology more info
enables PDZ domain binding	ISS Inferred from Sequence or Structural Similarity more info
enables antiporter activity	IDA Inferred from Direct Assay more info	PubMed
enables antiporter activity	TAS Traceable Author Statement more info
enables chloride channel activity	ISO Inferred from Sequence Orthology more info
enables monoatomic ion channel activity	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	ISO Inferred from Sequence Orthology more info
enables voltage-gated chloride channel activity	ISS Inferred from Sequence or Structural Similarity more info
enables voltage-gated monoatomic ion channel activity	ISO Inferred from Sequence Orthology more info
enables volume-sensitive chloride channel activity	IEA Inferred from Electronic Annotation more info
NOT enables volume-sensitive chloride channel activity	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
acts_upstream_of_or_within adult locomotory behavior	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in chloride transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in chloride transport	ISO Inferred from Sequence Orthology more info
involved_in monoatomic ion transport	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cell volume	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within neuron cellular homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within phagocytosis, engulfment	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within photoreceptor cell maintenance	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of reactive oxygen species biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within synaptic transmission, GABAergic	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within synaptic transmission, glutamatergic	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in synaptic vesicle lumen acidification	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within synaptic vesicle lumen acidification	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in synaptic vesicle lumen acidification	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in transmembrane transport	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in GABA-ergic synapse	IEA Inferred from Electronic Annotation more info
is_active_in GABA-ergic synapse	ISO Inferred from Sequence Orthology more info
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 apparatus	ISS Inferred from Sequence or Structural Similarity more info
located_in apical plasma membrane	ISO Inferred from Sequence Orthology more info
located_in axon terminus	IDA Inferred from Direct Assay more info	PubMed
is_active_in early endosome	IBA Inferred from Biological aspect of Ancestor more info
located_in early endosome	ISO Inferred from Sequence Orthology more info
located_in early endosome	ISS Inferred from Sequence or Structural Similarity more info
located_in early endosome membrane	IDA Inferred from Direct Assay more info	PubMed
located_in early endosome membrane	IEA Inferred from Electronic Annotation more info
located_in endosome	IDA Inferred from Direct Assay more info	PubMed
located_in endosome membrane	IDA Inferred from Direct Assay more info	PubMed
located_in external side of plasma membrane	IEA Inferred from Electronic Annotation more info
is_active_in glutamatergic synapse	IDA Inferred from Direct Assay more info	PubMed
is_active_in glutamatergic synapse	IMP Inferred from Mutant Phenotype more info	PubMed
is_active_in glutamatergic synapse	ISO Inferred from Sequence Orthology more info
located_in inhibitory synapse	ISO Inferred from Sequence Orthology more info	PubMed
located_in intracellular membrane-bounded organelle	ISO Inferred from Sequence Orthology more info
located_in late endosome	ISO Inferred from Sequence Orthology more info
located_in late endosome	ISS Inferred from Sequence or Structural Similarity more info
located_in late endosome membrane	IDA Inferred from Direct Assay more info	PubMed
located_in late endosome membrane	TAS Traceable Author Statement more info
located_in lysosomal membrane	IDA Inferred from Direct Assay more info	PubMed
located_in phagocytic vesicle	IEA Inferred from Electronic Annotation more info
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	PubMed
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
is_active_in postsynaptic membrane	ISO Inferred from Sequence Orthology more info
located_in recycling endosome	IDA Inferred from Direct Assay more info	PubMed
located_in recycling endosome membrane	IDA Inferred from Direct Assay more info	PubMed
located_in recycling endosome membrane	IEA Inferred from Electronic Annotation more info
located_in specific granule	IEA Inferred from Electronic Annotation more info
is_active_in synaptic vesicle	IBA Inferred from Biological aspect of Ancestor more info
located_in synaptic vesicle	IDA Inferred from Direct Assay more info	PubMed
located_in synaptic vesicle	ISO Inferred from Sequence Orthology more info	PubMed
located_in synaptic vesicle membrane	IEA Inferred from Electronic Annotation more info
is_active_in synaptic vesicle membrane	ISO Inferred from Sequence Orthology more info
located_in vesicle membrane	ISO Inferred from Sequence Orthology more info
located_in vesicle membrane	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: H(+)/Cl(-) exchange transporter 3

Names: chloride channel 3; chloride channel protein 3; chloride transporter ClC-3; clC-3

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_001416732.1 → NP_001403661.1 H(+)/Cl(-) exchange transporter 3 isoform g

Status: VALIDATED

Source sequence(s)

AC114920

UniProtKB/TrEMBL

E9Q2I1

Related

ENSMUSP00000105931.2, ENSMUST00000110302.8
NM_001416733.1 → NP_001403662.1 H(+)/Cl(-) exchange transporter 3 isoform h

Status: VALIDATED

Source sequence(s)

AC114920
NM_001416734.1 → NP_001403663.1 H(+)/Cl(-) exchange transporter 3 isoform i

Status: VALIDATED

Source sequence(s)

AC114920

UniProtKB/TrEMBL

Q790S0
NM_007711.4 → NP_031737.1 H(+)/Cl(-) exchange transporter 3 isoform a

See identical proteins and their annotated locations for NP_031737.1

Status: VALIDATED

Description

Transcript Variant: This variant (a) has multiple differences in the coding region and uses a downstream start codon, compared to variant b. It encodes isoform a, which is shorter than isoform b.

Source sequence(s)

AC114920

Consensus CDS

CCDS22323.1

UniProtKB/TrEMBL

Q6PGA5, Q790S0

Related

ENSMUSP00000091202.3, ENSMUST00000093490.9

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
NM_173873.2 → NP_776298.1 H(+)/Cl(-) exchange transporter 3 isoform b

See identical proteins and their annotated locations for NP_776298.1

Status: VALIDATED

Description

Transcript Variant: This variant (b) represents the predominant transcript and encodes isoform b.

Source sequence(s)

AC114920

Consensus CDS

CCDS52554.1

UniProtKB/Swiss-Prot

P51791, Q3TF45, Q8K4X0, Q8K4X1

UniProtKB/TrEMBL

A0A6Q6Q7B9

Related

ENSMUSP00000105930.2, ENSMUST00000110301.2

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
NM_173874.2 → NP_776299.1 H(+)/Cl(-) exchange transporter 3 isoform e

See identical proteins and their annotated locations for NP_776299.1

Status: VALIDATED

Description

Transcript Variant: This variant (e) includes an alternate exon in the 3' coding region that causes a frameshift, compared to variant b. It encodes isoform e which is longer and has a distinct C-terminus, compared to isoform b.

Source sequence(s)

AC114920

Consensus CDS

CCDS52555.1

UniProtKB/TrEMBL

Q3TTK0

Related

ENSMUSP00000004430.8, ENSMUST00000004430.14

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
NM_173876.4 → NP_776301.1 H(+)/Cl(-) exchange transporter 3 isoform c

See identical proteins and their annotated locations for NP_776301.1

Status: VALIDATED

Description

Transcript Variant: This variant (c) uses an alternate in-frame exon in the 5' coding region, compared to variant b. It encodes isoform c, which is shorter and has a distinct N-terminus compared to isoform b.

Source sequence(s)

AC114920

Consensus CDS

CCDS22322.1

UniProtKB/TrEMBL

Q6PGA5, Q8K4W8

Related

ENSMUSP00000058648.6, ENSMUST00000056508.12

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

RNA

NR_184390.1 RNA Sequence

Status: VALIDATED

Source sequence(s)

AC114920

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_000074.7 Reference GRCm39 C57BL/6J

Range

61363423..61436351 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_036153740.1 → XP_036009633.1 H(+)/Cl(-) exchange transporter 3 isoform X2

UniProtKB/TrEMBL

Q8K4W7

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
XM_017312552.3 → XP_017168041.1 H(+)/Cl(-) exchange transporter 3 isoform X2

UniProtKB/TrEMBL

Q8K4W7

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
XM_017312553.2 → XP_017168042.1 H(+)/Cl(-) exchange transporter 3 isoform X4

UniProtKB/TrEMBL

Q3UEX5

Conserved Domains (1) summary

cd03684
Location:136 → 588

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 ...