CLCNKB Gene

HGNC Family	Ion channels
Name	chloride channel, voltage-sensitive Kb
Description	The protein encoded by this gene is a member of the family of voltage-gated chloride channels. Chloride channels have several functions, including the regulation of cell volume, membrane potential stabilization, signal transduction and transepithelial transport. This gene is expressed predominantly in the kidney and may be important for renal salt reabsorption. Mutations in this gene are associated with autosomal recessive Bartter syndrome type 3 (BS3). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The ClC‐Kb chloride channel, encoded by the CLCNKB gene, is predominantly expressed in the basolateral membranes of cells in the thick ascending limb and distal convoluted tubule of the kidney, where it mediates Cl– reabsorption and thereby plays a crucial role in renal salt handling and fluid balance. Mutations in CLCNKB disrupt this reabsorption process and give rise to a spectrum of salt‐wasting tubulopathies such as classic Bartter syndrome, which is characterized by hypokalemic metabolic alkalosis, variable degrees of polyuria, growth retardation, and electrolyte disturbances – with clinical phenotypes that may even overlap with those seen in Gitelman syndrome ["}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "]. In contrast, gain‐of‐function polymorphisms such as T481S increase chloride current amplitude and have been linked to enhanced NaCl reabsorption and a predisposition to essential hypertension ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "]. Although some studies did not confirm an association of the T481S variant with blood pressure in certain populations ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "], the overall data highlight the sensitivity of ClC‐Kb function to both loss‐ and gain‐of‐function genetic alterations. Moreover, the activity and cell‐surface expression of ClC‐Kb are influenced by interacting proteins (for example, the accessory subunit barttin) and regulatory factors such as extracellular Ca²⁺ and pH, which modulate its gating and stability. Together, these findings underscore that ClC‐Kb is a key determinant of electrolyte homeostasis in the kidney, and that its dysfunction—whether through reduced surface expression or abnormal channel properties—not only underlies renal salt‐losing disorders but may also impact blood pressure regulation.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Melanie Peters, Nikola Jeck, Stephan Reinalter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical presentation of genetically defined patients with hypokalemic salt-losing tubulopathies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0002-9343(01)01086-5"}], "href": "https://doi.org/10.1016/s0002-9343(01"}, {"type": "t", "text": "01086-5) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11893344"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11893344"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Israel Zelikovic, Raymonde Szargel, Ali Hawash, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel mutation in the chloride channel gene, CLCNKB, as a cause of Gitelman and Bartter syndromes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Kidney Int (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1046/j.1523-1755.2003.00730.x"}], "href": "https://doi.org/10.1046/j.1523-1755.2003.00730.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12472765"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12472765"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Karine Brochard, Olivia Boyer, Anne Blanchard, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phenotype-genotype correlation in antenatal and neonatal variants of Bartter syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nephrol Dial Transplant (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/ndt/gfn689"}], "href": "https://doi.org/10.1093/ndt/gfn689"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19096086"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19096086"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Kandai Nozu, Xue Jun Fu, Koichi Nakanishi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular analysis of patients with type III Bartter syndrome: picking up large heterozygous deletions with semiquantitative PCR."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pediatr Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1203/PDR.0b013e318123fb90"}], "href": "https://doi.org/10.1203/PDR.0b013e318123fb90"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17622951"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17622951"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Wenbin Liang, Lihong Huang, Dongling Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Swelling-activated Cl- currents and intracellular CLC-3 are involved in proliferation of human pulmonary artery smooth muscle cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hypertens (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/HJH.0000000000000013"}], "href": "https://doi.org/10.1097/HJH.0000000000000013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24284495"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24284495"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "A Grill, I M Schießl, B Gess, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Salt-losing nephropathy in mice with a null mutation of the Clcnk2 gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Physiol (Oxf) (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/apha.12755"}], "href": "https://doi.org/10.1111/apha.12755"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27421685"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27421685"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Nikola Jeck, Siegfried Waldegger, Angelika Lampert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activating mutation of the renal epithelial chloride channel ClC-Kb predisposing to hypertension."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hypertension (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/01.HYP.0000129824.12959.f0"}], "href": "https://doi.org/10.1161/01.HYP.0000129824.12959.f0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15148291"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15148291"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Helen J L Speirs, William Y S Wang, Adam V Benjafield, et al. "}, {"type": "b", "children": [{"type": "t", "text": "No association with hypertension of CLCNKB and TNFRSF1B polymorphisms at a hypertension locus on chromosome 1p36."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hypertens (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/01.hjh.0000174300.73992.cc"}], "href": "https://doi.org/10.1097/01.hjh.0000174300.73992.cc"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16003175"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16003175"}]}]}]}
Synonyms	CLC-KB, CLCKB, CLC-K2
Proteins	CLCKB_HUMAN
NCBI Gene ID	1188
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CLCNKB has 3,832 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 110 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

CLCNKB Gene

Functional Associations

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

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by CLCNKB gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CLCNKB gene relative to other tissues from the Allen Brain Atlas Adult Human 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 CLCNKB 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 CLCNKB gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CLCNKB 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 CLCNKB 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 CLCNKB 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 CLCNKB 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 CLCNKB gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CLCNKB 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 CLCNKB gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CLCNKB 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 CLCNKB gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CLCNKB 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 CLCNKB 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 CLCNKB gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with CLCNKB 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 CLCNKB gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CLCNKB protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CLCNKB protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CLCNKB 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 CLCNKB 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 CLCNKB gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CLCNKB gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CLCNKB gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CLCNKB gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CLCNKB gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving CLCNKB gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving CLCNKB gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with CLCNKB 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 CLCNKB 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 CLCNKB 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 CLCNKB gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CLCNKB 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 CLCNKB 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 CLCNKB gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CLCNKB 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 CLCNKB from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with CLCNKB gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with CLCNKB gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.