CLIC1 Gene

HGNC Family	Ion channels
Name	chloride intracellular channel 1
Description	Chloride channels are a diverse group of proteins that regulate fundamental cellular processes including stabilization of cell membrane potential, transepithelial transport, maintenance of intracellular pH, and regulation of cell volume. Chloride intracellular channel 1 is a member of the p64 family; the protein localizes principally to the cell nucleus and exhibits both nuclear and plasma membrane chloride ion channel activity. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Chloride intracellular channel 1 (CLIC1) is a highly conserved protein that uniquely exists in both soluble and membrane‐integrated forms. Its ability to reversibly transition from a soluble monomer to a membrane‐incorporated channel is governed by redox and pH conditions. Under oxidative conditions, CLIC1 undergoes a conformational change—characterized by the formation of an intramolecular disulfide bond and dimerization—that exposes a hydrophobic surface required for membrane integration and subsequent chloride ion conductance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its channel activity, CLIC1 has been implicated in cell cycle regulation. Its plasma membrane expression is selectively observed during the G2/M phase, suggesting that the protein may play a role in progression through cell division."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n CLIC1 also links redox signalling to innate immune responses. In macrophages, following events such as potassium efflux and mitochondrial reactive oxygen species production, CLIC1 translocates to the plasma membrane where it facilitates chloride efflux that is essential for the assembly and activation of the NLRP3 inflammasome. This, in turn, promotes caspase‐1 activation and the secretion of inflammatory interleukin‑1β."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Similarly, in microglia, amyloid β stimulation up‐regulates CLIC1 expression and function, leading to enhanced cytokine release and contributing to neurotoxicity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In cancer, aberrant CLIC1 expression and its altered intracellular localization have been associated with tumor progression. Overexpression of CLIC1 in glioblastoma stem cells is correlated with increased proliferation and self‐renewal, while in colorectal and colon cancers, up‐regulated CLIC1 facilitates processes such as regulatory volume decrease that promote cell migration and invasion via ROS/ERK signalling pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": " In glioblastoma, CLIC1 is also found in extracellular vesicles, where its dose‐dependent effects further stimulate tumor growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings indicate that CLIC1 serves as a multifunctional protein bridging redox regulation, ion channel activity, and signal transduction. Through its redox‐dependent conformational changes and targeted membrane integration, CLIC1 modulates key cellular processes including cell division, inflammasome activation in immune cells, and mechanisms driving cancer cell invasion and proliferation.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Dene R Littler, Stephen J Harrop, W Douglas Fairlie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The intracellular chloride ion channel protein CLIC1 undergoes a redox-controlled structural transition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M308444200"}], "href": "https://doi.org/10.1074/jbc.M308444200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14613939"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14613939"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "S J Harrop, M Z DeMaere, W D Fairlie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Crystal structure of a soluble form of the intracellular chloride ion channel CLIC1 (NCC27) at 1.4-A resolution."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M107804200"}], "href": "https://doi.org/10.1074/jbc.M107804200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11551966"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11551966"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kristina Warton, Raffaella Tonini, W Douglas Fairlie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Recombinant CLIC1 (NCC27) assembles in lipid bilayers via a pH-dependent two-state process to form chloride ion channels with identical characteristics to those observed in Chinese hamster ovary cells expressing CLIC1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M203666200"}], "href": "https://doi.org/10.1074/jbc.M203666200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11978800"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11978800"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "S M Valenzuela, M Mazzanti, R Tonini, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The nuclear chloride ion channel NCC27 is involved in regulation of the cell cycle."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Physiol (2000)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1469-7793.2000.00541.x"}], "href": "https://doi.org/10.1111/j.1469-7793.2000.00541.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11195932"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11195932"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Lele Jiang, Kanin Salao, Hui Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Intracellular chloride channel protein CLIC1 regulates macrophage function through modulation of phagosomal acidification."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.110072"}], "href": "https://doi.org/10.1242/jcs.110072"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22956539"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22956539"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Raquel Domingo-Fernández, Rebecca C Coll, Jay Kearney, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The intracellular chloride channel proteins CLIC1 and CLIC4 induce IL-1β transcription and activate the NLRP3 inflammasome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M117.797126"}], "href": "https://doi.org/10.1074/jbc.M117.797126"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28576828"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28576828"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Gaia Novarino, Cinzia Fabrizi, Raffaella Tonini, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Involvement of the intracellular ion channel CLIC1 in microglia-mediated beta-amyloid-induced neurotoxicity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.1170-04.2004"}], "href": "https://doi.org/10.1523/JNEUROSCI.1170-04.2004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15190104"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15190104"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Matteo Setti, Nicoletta Savalli, Daniela Osti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional role of CLIC1 ion channel in glioblastoma-derived stem/progenitor cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Natl Cancer Inst (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/jnci/djt278"}], "href": "https://doi.org/10.1093/jnci/djt278"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24115360"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24115360"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Darinka Todorova Petrova, Abdul R Asif, Victor W Armstrong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of chloride intracellular channel protein 1 (CLIC1) and tumor protein D52 (TPD52) as potential biomarkers for colorectal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Biochem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.clinbiochem.2008.07.012"}], "href": "https://doi.org/10.1016/j.clinbiochem.2008.07.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18710659"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18710659"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Pan Wang, Yun Zeng, Tao Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Chloride intracellular channel 1 regulates colon cancer cell migration and invasion through ROS/ERK pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "World J Gastroenterol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3748/wjg.v20.i8.2071"}], "href": "https://doi.org/10.3748/wjg.v20.i8.2071"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24587680"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24587680"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Matteo Setti, Daniela Osti, Cristina Richichi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Extracellular vesicle-mediated transfer of CLIC1 protein is a novel mechanism for the regulation of glioblastoma growth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.5105"}], "href": "https://doi.org/10.18632/oncotarget.5105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26429879"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26429879"}]}]}]}
Synonyms	G6, NCC27, CL1C1
Proteins	CLIC1_HUMAN
NCBI Gene ID	1192
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CLIC1 has 7,988 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 111 datasets.

Click the + buttons to view associations for CLIC1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CLIC1 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CLIC1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of CLIC1 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of CLIC1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of CLIC1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CLIC1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of CLIC1 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CLIC1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CLIC1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CLIC1 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of CLIC1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CLIC1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CLIC1 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CLIC1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CLIC1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of CLIC1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CLIC1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CLIC1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CLIC1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with CLIC1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of CLIC1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CLIC1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CLIC1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CLIC1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of CLIC1 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CLIC1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with CLIC1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CLIC1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with CLIC1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with CLIC1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CLIC1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at CLIC1 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CLIC1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CLIC1 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing CLIC1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with CLIC1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with CLIC1 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of CLIC1 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with CLIC1 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing CLIC1 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of CLIC1 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.