Clcn3 chloride voltage-gated channel 3 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Clcn3provided by RGD
Official Full Name: chloride voltage-gated channel 3provided by RGD
Primary source: RGD:621219
See related: EnsemblRapid:ENSRNOG00000010682 AllianceGenome:RGD:621219
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: ClC-3
Summary: Enables voltage-gated chloride channel activity. Involved in chloride transport. Located in apical plasma membrane; inhibitory synapse; and synaptic vesicle. Is active in glutamatergic synapse and postsynaptic membrane. Orthologous to human CLCN3 (chloride voltage-gated channel 3). [provided by Alliance of Genome Resources, Jan 2025]
Expression: Biased expression in Brain (RPKM 191.4), Heart (RPKM 105.9) and 9 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 16p12

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	16	NC_086034.1 (34138004..34210984)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	16	NC_051351.1 (29127152..29200133)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	16	NC_005115.4 (32448821..32520649)

Chromosome 16 - NC_086034.1 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: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

A chloride channel in rat pancreatic acinar AR42J cells is sensitive to extracellular acidification and dependent on ROS.
Title: A chloride channel in rat pancreatic acinar AR42J cells is sensitive to extracellular acidification and dependent on ROS.
Data suggest that the chloride channel-3 (CLC-3) might be modulated by transforming growth factor beta (TGF-beta) / TGF-beta Receptor II (TGF- beta RII) signaling pathway during the development of diabetic encephalopathy (DE).
Title: TGF-beta/TGF-beta RII/CLC-3 axis promotes cognitive disorders in diabetes.
Knockdown of CLC-3 in hippocampal CA1 significantly attenuates the contextual fear memory, reduces spine density, induces defects of excitatory synaptic ultrastructure showed by the decreased PSD length, PSD thickness and active zone length, and impairs L-LTP induction and maintenance, and induces the synaptic NMDAR subunit composition to an increased GluN2A/GluN2B ratio pattern and reduces the activity of CaMKII-alpha.
Title: Knockdown of CLC-3 in the hippocampal CA1 impairs contextual fear memory.
Galactosemia caused the osmotic stress in lenses; it also markedly leads to the upregulations of aldose reductase, P-glycoprotein, and Clcn3 in lens epithelial cells, together resulting in obvious osmotic expansion in vitro and in vivo.
Title: Upregulations of Clcn3 and P-Gp Provoked by Lens Osmotic Expansion in Rat Galactosemic Cataract.
Results have shown that the expression of ClC-3 was reduced in hypertrophic H9c2 cells, primary rat neonatal cardiomyocytes and myocardium of C57/BL/6 mice and that ClC-3 played an important role in beta-adrenergic cardiac hypertrophy.
Title: ClC-3 chloride channel is involved in isoprenaline-induced cardiac hypertrophy.
Data suggest that ClC3/Clcn3 expression is up-regulated by mechanical stimulation (persistent static compression here) in osteoblastic cell line and appears to participate in mechanically sensitive osteogenesis and gene expression regulation.
Title: ClC-3 chloride channel functions as a mechanically sensitive channel in osteoblasts.
Integrin beta3 mediates cerebrovascular remodelling during hypertension via Src/ClC-3 signalling pathway.
Title: Integrin β3 mediates cerebrovascular remodelling through Src/ClC-3 volume-regulated Cl(-) channel signalling pathway.
Tyrosine 284 phosphorylation in the ClC-3 channel targeted by Src kinase is an important molecular mechanism for ClC-3 channel activation.
Title: Tyrosine 284 phosphorylation is required for ClC-3 chloride channel activation in vascular smooth muscle cells.
Data suggest that Clcn3 activity and chloride ion movement due to hypotonic solution are more prominent in smooth muscle cell from femoral artery than from femoral vein; regulation of Clcn3 activity via tyrosine phosphorylation is prominent in veins.
Title: Differences between femoral artery and vein smooth muscle cells in volume-regulated chloride channels.
Our results demonstrated for the first time that rat bone marrow endothelial progenitor cells expressed volume-sensitive chloride currents and the corresponding gene and protein Clcn3.
Title: Intermediate-conductance Ca(2+) -activated potassium and volume-sensitive chloride channels in endothelial progenitor cells from rat bone marrow mononuclear cells.

Submit: New GeneRIF Correction See all GeneRIFs (18)

General gene information

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Markers

UniSTS:238126 (e-PCR)
- UniSTS:238126

Cbx3 (e-PCR), detects polymorphism
- UniSTS:238126

RH142804 (e-PCR)
- UniSTS:232051

RH139046 (e-PCR)
- UniSTS:221132

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables PDZ domain 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	IEA Inferred from Electronic Annotation more info
enables antiporter activity	ISO Inferred from Sequence Orthology more info
enables antiporter activity	ISS Inferred from Sequence or Structural Similarity more info
enables chloride channel activity	IDA Inferred from Direct Assay more info	PubMed
enables chloride channel activity	ISO Inferred from Sequence Orthology more info
enables monoatomic ion channel activity	IDA Inferred from Direct Assay more info	PubMed
enables voltage-gated chloride channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables voltage-gated chloride channel activity	IDA Inferred from Direct Assay more info	PubMed
enables voltage-gated chloride channel activity	IEA Inferred from Electronic Annotation more info
enables voltage-gated monoatomic ion channel activity	IDA Inferred from Direct Assay more info	PubMed
enables volume-sensitive chloride channel activity	IEA Inferred from Electronic Annotation more info
NOT enables volume-sensitive chloride channel activity	ISO Inferred from Sequence Orthology more info
enables volume-sensitive chloride channel activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in adult locomotory behavior	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within adult locomotory behavior	ISO Inferred from Sequence Orthology more info
involved_in chloride transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in chloride transmembrane transport	ISO Inferred from Sequence Orthology more info
involved_in chloride transport	IDA Inferred from Direct Assay more info	PubMed
involved_in monoatomic ion transport	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell volume	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cell volume	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within neuron cellular homeostasis	ISO Inferred from Sequence Orthology more info
involved_in phagocytosis, engulfment	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within phagocytosis, engulfment	ISO Inferred from Sequence Orthology more info
involved_in photoreceptor cell maintenance	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within photoreceptor cell maintenance	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of reactive oxygen species biosynthetic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of reactive oxygen species biosynthetic process	ISO Inferred from Sequence Orthology more info
involved_in synaptic transmission, GABAergic	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within synaptic transmission, GABAergic	ISO Inferred from Sequence Orthology more info
involved_in synaptic transmission, glutamatergic	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within synaptic transmission, glutamatergic	ISO Inferred from Sequence Orthology more info
involved_in synaptic vesicle lumen acidification	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within synaptic vesicle lumen acidification	ISO Inferred from Sequence Orthology more info
involved_in synaptic vesicle lumen acidification	ISO Inferred from Sequence Orthology 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	IEA Inferred from Electronic Annotation 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	IDA Inferred from Direct Assay more info	PubMed
located_in axon terminus	IEA Inferred from Electronic Annotation more info
located_in axon terminus	ISO Inferred from Sequence Orthology more info
located_in cytoplasmic vesicle	ISO Inferred from Sequence Orthology more info
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	IEA Inferred from Electronic Annotation more info
located_in early endosome membrane	ISO Inferred from Sequence Orthology more info
located_in endosome	ISO Inferred from Sequence Orthology more info
located_in endosome membrane	ISO Inferred from Sequence Orthology more info
located_in endosome membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in external side of plasma membrane	IEA Inferred from Electronic Annotation more info
located_in external side of plasma membrane	ISO Inferred from Sequence Orthology more info
is_active_in glutamatergic synapse	IDA Inferred from Direct Assay more info	PubMed
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
is_active_in glutamatergic synapse	ISO Inferred from Sequence Orthology more info
located_in inhibitory synapse	IDA Inferred from Direct Assay 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	IEA Inferred from Electronic Annotation more info
located_in late endosome membrane	ISO Inferred from Sequence Orthology more info
located_in lysosomal membrane	IEA Inferred from Electronic Annotation more info
located_in lysosomal membrane	ISO Inferred from Sequence Orthology more info
located_in lysosomal membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in phagocytic vesicle	IEA Inferred from Electronic Annotation more info
located_in phagocytic vesicle	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	IDA Inferred from Direct Assay more info	PubMed
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 postsynaptic membrane	IDA Inferred from Direct Assay more info	PubMed
located_in recycling endosome	IEA Inferred from Electronic Annotation more info
located_in recycling endosome	ISO Inferred from Sequence Orthology more info
located_in recycling endosome	ISS Inferred from Sequence or Structural Similarity more info
located_in recycling endosome membrane	ISO Inferred from Sequence Orthology more info
located_in secretory granule	ISO Inferred from Sequence Orthology more info
located_in specific granule	IEA Inferred from Electronic Annotation more info
located_in specific granule	ISO Inferred from Sequence Orthology more info
located_in synapse	IDA Inferred from Direct Assay more info	PubMed
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
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 channel, voltage-sensitive 3; chloride transporter ClC-3; protein kinase C-regulated chloride channel

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_001413712.1 → NP_001400641.1 H(+)/Cl(-) exchange transporter 3 isoform 2

Status: VALIDATED

Source sequence(s)

JAXUCZ010000016

UniProtKB/TrEMBL

A0A0G2K2K6
NM_053363.3 → NP_445815.2 H(+)/Cl(-) exchange transporter 3 isoform 1

See identical proteins and their annotated locations for NP_445815.2

Status: VALIDATED

Source sequence(s)

JAXUCZ010000016

UniProtKB/Swiss-Prot

P51792, Q9R287

UniProtKB/TrEMBL

A6KIS2

Related

ENSRNOP00000045523.6, ENSRNOT00000050549.7

Conserved Domains (4) summary

COG0517
Location:656 → 801

CBS; CBS domain [Signal transduction mechanisms]

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:665 → 803

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:221 → 622

Voltage_CLC; Voltage gated chloride channel

RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

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

Reference GRCr8

Genomic

NC_086034.1 Reference GRCr8

Range

34138004..34210984

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_039094870.2 → XP_038950798.1 H(+)/Cl(-) exchange transporter 3 isoform X3

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_039094868.2 → XP_038950796.1 H(+)/Cl(-) exchange transporter 3 isoform X1

UniProtKB/TrEMBL

A0A8L2ULZ0

Related

ENSRNOP00000101815.1, ENSRNOT00000163967.1

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
XM_039094875.2 → XP_038950803.1 H(+)/Cl(-) exchange transporter 3 isoform X3

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_063275789.1 → XP_063131859.1 H(+)/Cl(-) exchange transporter 3 isoform X4

UniProtKB/TrEMBL

A6KIS3
XM_039094869.2 → XP_038950797.1 H(+)/Cl(-) exchange transporter 3 isoform X2

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
XM_039094871.2 → XP_038950799.1 H(+)/Cl(-) exchange transporter 3 isoform X3

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_039094873.2 → XP_038950801.1 H(+)/Cl(-) exchange transporter 3 isoform X3

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