WNK1
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.
Overview
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.
CIViC holds 1 clinical evidence item and 0 assertions across 1 variant.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · 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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
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.
- 3 · How drugs use it
No product in this corpus aims at WNK1 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:14540 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q9H4A3 (protein name, function text, keywords and locations (REST API)); CIViC gene WNK1 (1 evidence items, 0 assertions, 1 variants; diseases: Burkitt Lymphoma (GraphQL API, CC0))
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).
- Burkitt lymphoma: CIViC evidence names this disease
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: 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.
Latest papers
topQuery for this target: (TITLE:"WNK1" OR ABSTRACT:"WNK1" OR TITLE:"WNK lysine deficient protein kinase 1" OR ABSTRACT:"WNK lysine deficient protein kinase 1" OR TITLE:"Serine/threonine-protein kinase WNK1" OR ABSTRACT:"Serine/threonine-protein kinase WNK1" OR TITLE:"HSAN2" OR ABSTRACT:"HSAN2" OR TITLE:"PPP1R167" OR ABSTRACT:"PPP1R167" OR TITLE:"PRKWNK1" OR ABSTRACT:"PRKWNK1") 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 WNK1, not a curated reading list.
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