{"entity":{"id":"wnk2","kind":"target","name":"WNK2","aka":["WNK lysine deficient protein kinase 2","Serine/threonine-protein kinase WNK2","NY-CO-43","KIAA1760","SDCCAG43","PRKWNK2"],"tldr":"WNK2 (Serine/threonine-protein kinase WNK2) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as an oncogene driver and a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Sarcomas, Hepatocellular carcinoma, Mesothelioma and 2 more.","summary":"Serine/threonine-protein kinase component of the WNK2-SPAK/OSR1 kinase cascade, which plays an important role in the regulation of electrolyte homeostasis, cell signalling, survival, and proliferation. The WNK2-SPAK/OSR1 kinase cascade is composed of WNK2, which mediates phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK. Following activation, OXSR1/OSR1 and STK39/SPAK catalyse phosphorylation of ion cotransporters, regulating their activity.\n\nIntOGen calls it a driver in 4 cohorts (3 activating, 1 loss-of-function), covering Hepatocellular Carcinoma, Leiomyosarcoma, Pleural Mesothelioma.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:14542","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:14542"},{"label":"UniProt Q9Y3S1","url":"https://www.uniprot.org/uniprotkb/Q9Y3S1/entry"},{"label":"NCBI Gene 65268","url":"https://www.ncbi.nlm.nih.gov/gene/65268"},{"label":"Ensembl ENSG00000165238","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000165238"}],"tags":["cancer-genes-wave"],"related":["intogen"],"cancers":["sarcoma","hcc","mesothelioma","leiomyosarcoma","pleural-mesothelioma"],"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: IntOGen calls it an activating (Act) driver in 3 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 1 cohort. Evidence tier \"cohort-driver\" 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":"WNK2","role":["oncogene-driver","tumour-suppressor"],"evidenceTier":"cohort-driver","sources":[{"label":"HGNC HGNC:14542","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:14542","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q9Y3S1","url":"https://www.uniprot.org/uniprotkb/Q9Y3S1/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"IntOGen WNK2","url":"https://www.intogen.org/search?gene=WNK2","note":"driver in 4 cohorts (Act 3, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"hgnc":"HGNC:14542","ensembl":"ENSG00000165238","uniprot":"Q9Y3S1","entrez":"65268","biology":"Serine/threonine-protein kinase component of the WNK2-SPAK/OSR1 kinase cascade, which plays an important role in the regulation of electrolyte homeostasis, cell signalling, survival, and proliferation. The WNK2-SPAK/OSR1 kinase cascade is composed of WNK2, which mediates phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK. Following activation, OXSR1/OSR1 and STK39/SPAK catalyse phosphorylation of ion cotransporters, regulating their activity. Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively. Activates SLC12A2, SCNN1A, SCNN1B, SCNN1D and SGK1 and inhibits SLC12A5. Negatively regulates the EGF-induced activation of the ERK/MAPK-pathway and the downstream cell cycle progression. Location: Cytoplasm; Cell membrane (UniProt). Locus 9q22.31 (HGNC).","whereFound":["Sarcomas: IntOGen driver in 2 cohorts (LMS)","Hepatocellular carcinoma: IntOGen driver in 1 cohort (HCC)","Mesothelioma: IntOGen driver in 1 cohort (PLMESO)","Leiomyosarcoma: IntOGen driver in 2 cohorts (LMS)","Pleural mesothelioma: IntOGen driver in 1 cohort (PLMESO)"],"targetClass":"kinase","prevalence":[]},"route":"/targets/wnk2/","neighbours":{"collection":[{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"}],"cancer":[{"id":"hcc","kind":"cancer","name":"Hepatocellular carcinoma","route":"/cancers/hcc/"},{"id":"leiomyosarcoma","kind":"cancer","name":"Leiomyosarcoma","route":"/cancers/leiomyosarcoma/"},{"id":"mesothelioma","kind":"cancer","name":"Mesothelioma","route":"/cancers/mesothelioma/"},{"id":"pleural-mesothelioma","kind":"cancer","name":"Pleural mesothelioma","route":"/cancers/pleural-mesothelioma/"},{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"}]}}