WNK2: WNK Lysine Deficient Protein Kinase 2
A serine/threonine protein kinase involved in ion transport, cell signaling, and tumor suppression.
Gene Information Card
| Symbol | WNK2 |
|---|---|
| Full Name | WNK lysine deficient protein kinase 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 9q22.31 |
| NCBI Gene ID | 65268 ncbi.nlm.nih.gov/gene/65268 |
| Ensembl ID | ENSG00000165238 |
| UniProt ID | Q9Y3S1 |
| OMIM ID | 606249 |
| HGNC ID | 14542 |
| Aliases | KIAA1760, PRKWNK2, NY-CO-43 |
Description
WNK2 (WNK lysine deficient protein kinase 2) is a member of the WNK family of serine/threonine protein kinases, characterized by the absence of a conserved lysine in the catalytic domain. It plays a critical role in regulating ion transport, cell signaling, and cytoskeletal organization. WNK2 is implicated in blood pressure regulation and acts as a tumor suppressor in various cancers, including glioblastoma and hepatocellular carcinoma.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Glioblastoma | WNK2 expression is frequently silenced by promoter hypermethylation, leading to loss of tumor suppressor function and increased cell proliferation. | PMID: 17634560 |
| Hepatocellular carcinoma | Reduced WNK2 expression correlates with poor prognosis; loss promotes cell migration and invasion via altered actin dynamics. | PMID: 24755471 |
| Essential hypertension | WNK2 variants may contribute to blood pressure regulation through modulation of ion transporters (e.g., NCC, NKCC). | PMID: 18577715 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Kidney | 8.3 | Low |
| Heart | 6.1 | Low |
| Liver | 4.7 | Low |
| Lung | 3.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | High expression in embryonic kidney cells |
| U87MG | 2.1 | Low expression in glioblastoma cell line |
| HepG2 | 5.8 | Moderate expression in liver cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | Rare | Loss of function; truncation of kinase domain |
| c.567G>A (p.Trp189*) | Nonsense | Rare | Loss of function; premature stop codon |
| c.2101A>G (p.Thr701Ala) | Missense | Unknown | Potential impact on kinase activity |
Mutation functional classification
Loss of Function (LOF)
Nonsense mutations (e.g., p.Arg412*, p.Trp189*) lead to truncated, non-functional protein, consistent with tumor suppressor role.
Gain of Function (GOF)
No gain-of-function mutations have been reported in WNK2.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for WNK2.
View complete mutation data：
Gene Ontology (GO)
Pathways
• WNK signaling pathway (Reactome: R-HSA-2672351)
• Ion transport by WNK kinases (Reactome: R-HSA-5621480)
• Regulation of actin cytoskeleton (KEGG: hsa04810)
Protein Summary
WNK2 is a 2296-amino acid serine/threonine protein kinase with a unique catalytic domain lacking the canonical lysine. It localizes to the cytoplasm and nucleus, and regulates ion cotransporters (e.g., NCC, NKCC) via phosphorylation of SPAK/OSR1 kinases. WNK2 also modulates actin polymerization and cell migration. Its expression is frequently silenced by hypermethylation in cancers, supporting a tumor suppressor function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| WNK2 Knockout HEK293 Cell Line | EDJ-KQ16146 | Human | 65268 | Details Get a Quote |
| WNK2 Knockout A-549 Cell Line | EDJ-KQ47330 | Human | 65268 | Details Get a Quote |
| WNK2 Knockout HCT 116 Cell Line | EDJ-KQ47331 | Human | 65268 | Details Get a Quote |
| WNK2 Knockout HeLa Cell Line | EDJ-KQ47332 | Human | 65268 | Details Get a Quote |
