WNK1 Gene

HGNC Family	Minor histocompatibility antigens, Protein phosphatase 1 regulatory subunits (PPP1R)
Name	WNK lysine deficient protein kinase 1
Description	This gene encodes a member of the WNK subfamily of serine/threonine protein kinases. The encoded protein may be a key regulator of blood pressure by controlling the transport of sodium and chloride ions. Mutations in this gene have been associated with pseudohypoaldosteronism type II and hereditary sensory neuropathy type II. Alternatively spliced transcript variants encoding different isoforms have been described but the full-length nature of all of them has yet to be determined.[provided by RefSeq, May 2010]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nWNK1 is a unique serine–threonine kinase that sits at the apex of a signaling cascade regulating ion transport. It phosphorylates and activates the SPAK and OSR1 kinases, which in turn target key cation–chloride cotransporters (NKCC1, NKCC2, NCC, and KCC) to modulate ion flux under osmotic or hypotonic stress. In this capacity, WNK1-mediated phosphorylation constitutes a central mechanism whereby cells rapidly adjust ion balance in response to extracellular disturbances, thereby impacting blood pressure and electrolyte homeostasis. (See."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in activating downstream kinases, WNK1 functions as an intrinsic sensor and regulator through several regulatory mechanisms. Its catalytic activity is modulated directly by intracellular chloride binding—which stabilizes an inactive conformation by inhibiting autophosphorylation—and by phosphorylation at critical residues (such as Ser382 and Thr60) in response to hyperosmolar conditions or PI3K-activating hormones. Complex alternative promoter usage and splicing yield distinct isoforms, including a long, kinase‐active WNK1 and a kidney‐specific, kinase‐defective variant (KS-WNK1) that exerts opposing effects—for example, in controlling ROMK1 channel trafficking and in organizing “WNK bodies” within the distal convoluted tubule. Such isoform-specific actions are essential for fine-tuning renal Na+ and K+ handling and blood pressure regulation. (See."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "12"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nWNK1 is further regulated by cross-talk with other signaling pathways and by genetic variation. It is a substrate for protein kinase B (Akt) and SGK1, which phosphorylate key threonine residues to further modulate its regulatory capacity on ROMK endocytosis. Moreover, WNK1 has been shown to phosphorylate components such as synaptotagmin 2—thereby altering Ca2+ sensitivity and influencing membrane protein trafficking—and genetic polymorphisms in its coding and regulatory regions can predict variations in antihypertensive responses. In certain neoplasms, including chronic lymphocytic leukemia and chordoma, aberrant WNK1 activity or fusion events further underscore its broader relevance as a molecular driver. (See."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "19"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tetsuo Moriguchi, Seiichi Urushiyama, Naoki Hisamoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "WNK1 regulates phosphorylation of cation-chloride-coupled cotransporters via the STE20-related kinases, SPAK and OSR1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M510042200"}], "href": "https://doi.org/10.1074/jbc.M510042200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16263722"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16263722"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Alexander T Piala, Thomas M Moon, Radha Akella, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Chloride sensing by WNK1 involves inhibition of autophosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Signal (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/scisignal.2005050"}], "href": "https://doi.org/10.1126/scisignal.2005050"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24803536"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24803536"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Alberto C Vitari, Jacob Thastrup, Fatema H Rafiqi, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "WNK1 and OSR1 regulate the Na+, K+, 2Cl- cotransporter in HeLa cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0604607103"}], "href": "https://doi.org/10.1073/pnas.0604607103"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16832045"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16832045"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ahmed Lazrak, Zhen Liu, Chou-Long Huang "}, {"type": "b", "children": [{"type": "t", "text": "Antagonistic regulation of ROMK by long and kidney-specific WNK1 isoforms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0510609103"}], "href": "https://doi.org/10.1073/pnas.0510609103"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16428287"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16428287"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Guocheng He, Hao-Ran Wang, Shao-Kuei Huang, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "WNK1 kinase polymorphism and blood pressure response to a thiazide diuretic."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hypertension (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/01.HYP.0000186240.81996.57"}], "href": "https://doi.org/10.1161/01.HYP.0000186240.81996.57"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16172412"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16172412"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Alberto C Vitari, Maria Deak, Barry J Collins, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Alternatively spliced proline-rich cassettes link WNK1 to aldosterone action."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI75245"}], "href": "https://doi.org/10.1172/JCI75245"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26241057"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26241057"}]}]}]}
Synonyms	HSN2, KDP, HSAN2, PPP1R167, PRKWNK1
Proteins	WNK1_HUMAN
NCBI Gene ID	65125
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

WNK1 has 12,303 functional associations with biological entities spanning 8 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) extracted from 146 datasets.

Click the + buttons to view associations for WNK1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

WNK1 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 WNK1 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 WNK1 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 WNK1 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 WNK1 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 WNK1 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 WNK1 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 WNK1 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 WNK1 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 WNK1 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 WNK1 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 WNK1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of WNK1 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 WNK1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with WNK1 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with WNK1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with WNK1 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 WNK1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of WNK1 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 WNK1 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 WNK1 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with WNK1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of WNK1 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing WNK1 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of WNK1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing WNK1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing WNK1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with WNK1 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 WNK1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing WNK1 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of WNK1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with WNK1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with WNK1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with WNK1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DGIdb Drug Targets 2026	interacting drugs for WNK1 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving WNK1 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving WNK1 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with WNK1 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 WNK1 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 WNK1 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 WNK1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.