CLCN7 Gene

HGNC Family	Ion channels, Protein phosphatase 1 regulatory subunits (PPP1R)
Name	chloride channel, voltage-sensitive 7
Description	The product of this gene belongs to the CLC chloride channel family of proteins. Chloride channels play important roles in the plasma membrane and in intracellular organelles. This gene encodes chloride channel 7. Defects in this gene are the cause of osteopetrosis autosomal recessive type 4 (OPTB4), also called infantile malignant osteopetrosis type 2 as well as the cause of autosomal dominant osteopetrosis type 2 (OPTA2), also called autosomal dominant Albers-Schonberg disease or marble disease autosoml dominant. Osteopetrosis is a rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. OPTA2 is the most common form of osteopetrosis, occurring in adolescence or adulthood. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CLCN7 is a late endosomal/lysosomal member of the CLC family that functions primarily as a chloride‐proton (Cl<sup>−</sup>/H<sup>+</sup>) antiporter. Its activity provides the essential counterion conductance that permits vacuolar H<sup>+</sup>-ATPases to efficiently acidify lysosomes and the resorption lacunae generated by osteoclasts. In osteoclasts, proper CLCN7 function is critical for bone resorption because it facilitates acidification of the bone–cell interface; although osteoclast formation may be preserved, mutations that impair CLCN7 activity result in insufficient acidification and greatly reduced resorption efficiency. Moreover, CLCN7 does not operate alone but assembles into a complex with the accessory β‐subunit OSTM1, which is required for its stability, proper lysosomal targeting, and full transport activity. Mutations in the CLCN7 gene are directly linked to osteopetrosis and are further associated with lysosomal storage disease and, in some cases, neurodegeneration, underscoring the transporter’s broader role in maintaining lysosomal protein degradation in diverse tissues. Furthermore, studies using point mutations that convert CLCN7 into an uncoupled chloride conductor have demonstrated that while chloride conductance per se may partially support osteoclast function, the full Cl<sup>−</sup>/H<sup>+</sup> exchange activity of CLCN7 is necessary for normal lysosomal chloride accumulation and cell homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, CLCN7 plays a pivotal role in lysosomal acidification and osteoclast-mediated bone resorption by acting as the major pathway for chloride ions across the lysosomal membrane. Its functional integrity—ensured through proper complex formation with OSTM1—is indispensable for maintaining the acidic environment required for lysosomal enzyme activity and for effective bone turnover. Disruption of this system as a result of CLCN7 mutations results in a spectrum of pathologic conditions, ranging from osteopetrosis and abnormal bone mineral density to lysosomal storage and neurodegenerative disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Austin R Graves, Patricia K Curran, Carolyn L Smith, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Cl-/H+ antiporter ClC-7 is the primary chloride permeation pathway in lysosomes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature06907"}], "href": "https://doi.org/10.1038/nature06907"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18449189"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18449189"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Dagmar Kasper, Rosa Planells-Cases, Jens C Fuhrmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of the chloride channel ClC-7 leads to lysosomal storage disease and neurodegeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.emboj.7600576"}], "href": "https://doi.org/10.1038/sj.emboj.7600576"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15706348"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15706348"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Philipp F Lange, Lena Wartosch, Thomas J Jentsch, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ClC-7 requires Ostm1 as a beta-subunit to support bone resorption and lysosomal function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature04535"}], "href": "https://doi.org/10.1038/nature04535"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16525474"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16525474"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Stefanie Weinert, Sabrina Jabs, Chayarop Supanchart, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lysosomal pathology and osteopetrosis upon loss of H+-driven lysosomal Cl- accumulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1188072"}], "href": "https://doi.org/10.1126/science.1188072"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20430974"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20430974"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Kim Henriksen, Jeppe Gram, Sophie Schaller, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of osteoclasts from patients harboring a G215R mutation in ClC-7 causing autosomal dominant osteopetrosis type II."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/S0002-9440(10)63712-1"}], "href": "https://doi.org/10.1016/S0002-9440(10"}, {"type": "t", "text": "63712-1) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15111300"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15111300"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Amitabha Majumdar, Estibaliz Capetillo-Zarate, Dana Cruz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Degradation of Alzheimer's amyloid fibrils by microglia requires delivery of ClC-7 to lysosomes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E10-09-0745"}], "href": "https://doi.org/10.1091/mbc.E10-09-0745"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21441306"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21441306"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ana Belinda Campos-Xavier, Jorge M Saraiva, Letícia M Ribeiro, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Chloride channel 7 (CLCN7) gene mutations in intermediate autosomal recessive osteopetrosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Genet (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00439-002-0861-9"}], "href": "https://doi.org/10.1007/s00439-002-0861-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12522560"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12522560"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Patrick Schulz, Johannes Werner, Tobias Stauber, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The G215R mutation in the Cl-/H+-antiporter ClC-7 found in ADO II osteopetrosis does not abolish function but causes a severe trafficking defect."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0012585"}], "href": "https://doi.org/10.1371/journal.pone.0012585"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20830208"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20830208"}]}]}]}
Synonyms	OPTA2, OPTB4, CLC7, CLC-7, PPP1R63
Proteins	CLCN7_HUMAN
NCBI Gene ID	1186
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CLCN7 has 7,939 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 130 datasets.

Click the + buttons to view associations for CLCN7 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CLCN7 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 CLCN7 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 CLCN7 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of CLCN7 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of CLCN7 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 CLCN7 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 CLCN7 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 CLCN7 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 CLCN7 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 CLCN7 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of CLCN7 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CLCN7 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 CLCN7 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CLCN7 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CLCN7 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 CLCN7 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CLCN7 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 CLCN7 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with CLCN7 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with CLCN7 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CLCN7 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CLCN7 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CLCN7 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing CLCN7 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CLCN7 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 CLCN7 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 CLCN7 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CLCN7 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with CLCN7 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of CLCN7 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 CLCN7 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving CLCN7 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving CLCN7 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with CLCN7 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with CLCN7 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 CLCN7 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 CLCN7 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 CLCN7 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CLCN7 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 CLCN7 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 CLCN7 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.