Clic4 chloride intracellular channel 4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Clic4provided by MGI
Official Full Name: chloride intracellular channel 4provided by MGI
Primary source: MGI:MGI:1352754
See related: Ensembl:ENSMUSG00000037242 AllianceGenome:MGI:1352754
Gene type: protein coding
RefSeq status: PROVISIONAL
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: TU-74; mc3s5; D0Jmb3; mtCLIC
Summary: Predicted to enable chloride channel activity. Involved in keratinocyte differentiation. Acts upstream of or within several processes, including endothelial cell morphogenesis; vacuolar acidification; and vasculature development. Located in mitochondrion. Is expressed in brain; metanephros; skin; and spleen. Orthologous to human CLIC4 (chloride intracellular channel 4). [provided by Alliance of Genome Resources, Jul 2025]
Expression: Ubiquitous expression in lung adult (RPKM 93.5), bladder adult (RPKM 63.6) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 4 D3; 4 67.19 cM

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	4	NC_000070.7 (134941280..135000071, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	4	NC_000070.6 (135213969..135272760, complement)

Chromosome 4 - NC_000070.7 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: 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?

Chloride intracellular channel 4 blockade improves cognition in mice with Alzheimer's disease: CLIC4 protein expression and tau protein hyperphosphorylation.
Title: Chloride intracellular channel 4 blockade improves cognition in mice with Alzheimer's disease: CLIC4 protein expression and tau protein hyperphosphorylation.
CLIC4 Regulates Endothelial Barrier Control by Mediating PAR1 Signaling via RhoA.
Title: CLIC4 Regulates Endothelial Barrier Control by Mediating PAR1 Signaling via RhoA.
The oxidoreductase CLIC4 is required to maintain mitochondrial function and resistance to exogenous oxidants in breast cancer cells.
Title: The oxidoreductase CLIC4 is required to maintain mitochondrial function and resistance to exogenous oxidants in breast cancer cells.
Chloride intracellular channel 4 (CLIC4) expression profile in the mouse medial prefrontal cortex and its regulation by ethanol.
Title: Chloride intracellular channel 4 (CLIC4) expression profile in the mouse medial prefrontal cortex and its regulation by ethanol.
Retinal pigment epithelium-specific CLIC4 mutant is a mouse model of dry age-related macular degeneration.
Title: Retinal pigment epithelium-specific CLIC4 mutant is a mouse model of dry age-related macular degeneration.
CLIC1 and CLIC4 mediate endothelial S1P receptor signaling to facilitate Rac1 and RhoA activity and function.
Title: CLIC1 and CLIC4 mediate endothelial S1P receptor signaling to facilitate Rac1 and RhoA activity and function.
Results indicate CLICs (CLIC1, CLIC4 and CLIC5)-dependent chloride efflux as an essential and proximal upstream event for NLRP3 activation.
Title: CLICs-dependent chloride efflux is an essential and proximal upstream event for NLRP3 inflammasome activation.
Data, including data from studies in primary cells from knockout mice, suggest Clic1 and Clic4 participate in signaling interleukin 1beta secretion and in activation of Nlrp3 inflammasomes; in LPS macrophage activation, Clic1 and Clic4 are translocated to nucleus/cell membranes. (Clic1 = chloride intracellular channel 1; Clic4 = chloride intracellular channel 4, mitochondrial; Nlrp3 = NLR family pyrin domain containing 3)
Title: The intracellular chloride channel proteins CLIC1 and CLIC4 induce IL-1β transcription and activate the NLRP3 inflammasome.
study reports an alternately-spliced form of Smad7, Smad7Delta, that is induced by TGF-beta and CLIC4, is a dominant inhibitor of Smad7 and enhances TGF-beta signaling
Title: Elevating CLIC4 in Multiple Cell Types Reveals a TGF- Dependent Induction of a Dominant Negative Smad7 Splice Variant.
The findings indicate that CLIC4/CLIC5A-mediated ERM activation is required for maintenance of the glomerular capillary architecture.
Title: Both CLIC4 and CLIC5A activate ERM proteins in glomerular endothelium.

Submit: New GeneRIF Correction See all GeneRIFs (24)

Variation

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Alleles

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

Endonuclease-mediated (5)
Gene trapped (2)
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

D11Bhm20 (e-PCR), detects polymorphism
- UniSTS:141619

D9Mit34.1 (e-PCR), detects polymorphism
- UniSTS:131903

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables chloride channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables chloride channel activity	IEA Inferred from Electronic Annotation more info
enables chloride channel activity	ISO Inferred from Sequence Orthology more info	PubMed
enables oxidoreductase activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-containing complex binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within angiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within branching morphogenesis of an epithelial tube	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to calcium ion	IEA Inferred from Electronic Annotation more info
involved_in cellular response to calcium ion	ISO Inferred from Sequence Orthology more info
involved_in chloride transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in chloride transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in chloride transport	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within chloride transport	ISO Inferred from Sequence Orthology more info	PubMed
acts_upstream_of_or_within endothelial cell morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in epidermal cell differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within fertilization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in keratinocyte differentiation	IEA Inferred from Electronic Annotation more info
involved_in keratinocyte differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in keratinocyte differentiation	ISO Inferred from Sequence Orthology more info
involved_in monoatomic ion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in monoatomic ion transport	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within multicellular organism growth	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cell migration	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cell migration	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cell migration	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within retina vasculature morphogenesis in camera-type eye	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within vacuolar acidification	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in anchoring junction	IEA Inferred from Electronic Annotation more info
located_in apical part of cell	IEA Inferred from Electronic Annotation more info
located_in apical part of cell	ISO Inferred from Sequence Orthology more info
located_in cell surface	IEA Inferred from Electronic Annotation more info
located_in cell surface	ISO Inferred from Sequence Orthology more info
located_in cell-cell junction	IEA Inferred from Electronic Annotation more info
located_in cell-cell junction	ISO Inferred from Sequence Orthology more info
located_in centrosome	IEA Inferred from Electronic Annotation more info
located_in centrosome	ISO Inferred from Sequence Orthology more info
part_of chloride channel complex	IEA Inferred from Electronic Annotation more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
located_in cytoplasmic vesicle	IEA Inferred from Electronic Annotation more info
located_in cytoplasmic vesicle membrane	IEA Inferred from Electronic Annotation 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 membrane	IBA Inferred from Biological aspect of Ancestor more info
colocalizes_with microtubule cytoskeleton	IEA Inferred from Electronic Annotation more info
colocalizes_with microtubule cytoskeleton	ISO Inferred from Sequence Orthology more info
located_in microvillus	IEA Inferred from Electronic Annotation more info
located_in microvillus	ISO Inferred from Sequence Orthology more info
located_in midbody	IEA Inferred from Electronic Annotation more info
located_in midbody	ISO Inferred from Sequence Orthology more info
located_in mitochondrial outer membrane	ISO Inferred from Sequence Orthology more info
located_in mitochondrion	HDA more info	PubMed
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrion	IEA Inferred from Electronic Annotation more info
located_in mitochondrion	ISO Inferred from Sequence Orthology more info
part_of monoatomic ion channel complex	IEA Inferred from Electronic Annotation more info
located_in nuclear matrix	IEA Inferred from Electronic Annotation more info
located_in nuclear matrix	ISO Inferred from Sequence Orthology more info
located_in nucleus	IEA Inferred from Electronic Annotation more info
located_in perinuclear region of cytoplasm	IEA Inferred from Electronic Annotation more info
located_in perinuclear region of cytoplasm	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: chloride intracellular channel protein 4

Names: chloride intracellular channel 4 (mitochondrial); glutaredoxin-like oxidoreductase CLIC4; mc3s5/mtCLIC

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.