# WNK2

Source: https://onco.cc/targets/wnk2/  
OnCo record `wnk2` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

IntOGen calls it a driver in 4 cohorts (3 activating, 1 loss-of-function), covering Hepatocellular Carcinoma, Leiomyosarcoma, Pleural Mesothelioma.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: WNK lysine deficient protein kinase 2; Serine/threonine-protein kinase WNK2; NY-CO-43; KIAA1760; SDCCAG43; PRKWNK2
- Tags: cancer-genes-wave
- Symbol: WNK2
- Class: kinase
- 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).
- Where found: 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

- 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.

## Sources

- HGNC HGNC:14542: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:14542
- UniProt Q9Y3S1: https://www.uniprot.org/uniprotkb/Q9Y3S1/entry
- NCBI Gene 65268: https://www.ncbi.nlm.nih.gov/gene/65268
- Ensembl ENSG00000165238: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000165238

## Connected records

- collections: [IntOGen](https://onco.cc/collections/intogen/)
- cancers: [Hepatocellular carcinoma](https://onco.cc/cancers/hcc/), [Leiomyosarcoma](https://onco.cc/cancers/leiomyosarcoma/), [Mesothelioma](https://onco.cc/cancers/mesothelioma/), [Pleural mesothelioma](https://onco.cc/cancers/pleural-mesothelioma/), [Sarcomas (soft tissue, bone, GIST)](https://onco.cc/cancers/sarcoma/)

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JSON: https://onco.cc/api/v1/entities/wnk2.json