{"entity":{"id":"wnk1","kind":"target","name":"WNK1","aka":["WNK lysine deficient protein kinase 1","Serine/threonine-protein kinase WNK1","HSAN2","PPP1R167","PRKWNK1","HSN2"],"tldr":"WNK1 (Serine/threonine-protein kinase WNK1) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Burkitt lymphoma.","summary":"Serine/threonine-protein kinase component of the WNK1-SPAK/OSR1 kinase cascade, which acts as a key regulator of blood pressure and regulatory volume increase by promoting ion influx. WNK1 mediates regulatory volume increase in response to hyperosmotic stress by acting as a molecular crowding sensor, which senses cell shrinkage and mediates formation of a membraneless compartment by undergoing liquid-liquid phase separation. The membraneless compartment concentrates WNK1 with its substrates, OXSR1/OSR1 and STK39/SPAK, promoting WNK1-dependent phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK.\n\nCIViC holds 1 clinical evidence item and 0 assertions across 1 variant.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:14540","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:14540"},{"label":"UniProt Q9H4A3","url":"https://www.uniprot.org/uniprotkb/Q9H4A3/entry"},{"label":"NCBI Gene 65125","url":"https://www.ncbi.nlm.nih.gov/gene/65125"},{"label":"Ensembl ENSG00000060237","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000060237"}],"tags":["cancer-genes-wave"],"related":["civic"],"cancers":["burkitt-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: CIViC holds 1 clinical evidence items on its variants. Evidence tier \"clinical-evidence\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"WNK1","role":["biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:14540","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:14540","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q9H4A3","url":"https://www.uniprot.org/uniprotkb/Q9H4A3/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene WNK1","url":"https://civicdb.org/features/14591","note":"1 evidence items, 0 assertions, 1 variants; diseases: Burkitt Lymphoma (GraphQL API, CC0)"}],"hgnc":"HGNC:14540","ensembl":"ENSG00000060237","uniprot":"Q9H4A3","entrez":"65125","biology":"Serine/threonine-protein kinase component of the WNK1-SPAK/OSR1 kinase cascade, which acts as a key regulator of blood pressure and regulatory volume increase by promoting ion influx. WNK1 mediates regulatory volume increase in response to hyperosmotic stress by acting as a molecular crowding sensor, which senses cell shrinkage and mediates formation of a membraneless compartment by undergoing liquid-liquid phase separation. The membraneless compartment concentrates WNK1 with its substrates, OXSR1/OSR1 and STK39/SPAK, promoting WNK1-dependent phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK. Following activation, OXSR1/OSR1 and STK39/SPAK catalyse phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A5/KCC2 and SLC12A6/KCC3, regulating their activity. Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion efflux. Also acts as a regulator of angiogenesis in endothelial cells via activation of OXSR1/OSR1 and STK39/SPAK: activation of OXSR1/OSR1 regulates chemotaxis and invasion, while STK39/SPAK regulates endothelial cell proliferation. Location: Cytoplasm; Nucleus; Cytoplasm, cytoskeleton, spindle (UniProt). Locus 12p13.33 (HGNC).","whereFound":["Burkitt lymphoma: CIViC evidence names this disease"],"targetClass":"kinase","prevalence":[]},"route":"/targets/wnk1/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"}],"cancer":[{"id":"burkitt-lymphoma","kind":"cancer","name":"Burkitt lymphoma","route":"/cancers/burkitt-lymphoma/"}]}}