WNK2
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.
Overview
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.
IntOGen calls it a driver in 4 cohorts (3 activating, 1 loss-of-function), covering Hepatocellular Carcinoma, Leiomyosarcoma, Pleural Mesothelioma.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · 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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
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.
- 3 · How drugs use it
No product in this corpus aims at WNK2 yet. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
External identifiers
Sources: HGNC HGNC:14542 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q9Y3S1 (protein name, function text, keywords and locations (REST API)); IntOGen WNK2 (driver in 4 cohorts (Act 3, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
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).
- 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)
Notes
top- 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.
Latest papers
topQuery for this target: (TITLE:"WNK2" OR ABSTRACT:"WNK2" OR TITLE:"WNK lysine deficient protein kinase 2" OR ABSTRACT:"WNK lysine deficient protein kinase 2" OR TITLE:"Serine/threonine-protein kinase WNK2" OR ABSTRACT:"Serine/threonine-protein kinase WNK2" OR TITLE:"NY-CO-43" OR ABSTRACT:"NY-CO-43" OR TITLE:"KIAA1760" OR ABSTRACT:"KIAA1760" OR TITLE:"SDCCAG43" OR ABSTRACT:"SDCCAG43") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about WNK2, not a curated reading list.
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