{"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"}],"specificitySources":[],"hgnc":"HGNC:14542","ensembl":"ENSG00000165238","uniprot":"Q9Y3S1","entrez":"65268","firstDescribed":2000,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Nagase et al, DNA Res, 2000, \"Prediction of the coding sequences of unidentified human genes. XIX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/11214970/","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/"}]}}