WNK4
WNK Lysine Deficient Protein Kinase 4
Gene Information Card
| Symbol | WNK4 |
|---|---|
| Full Name | WNK lysine deficient protein kinase 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 17q21.2 |
| NCBI Gene ID | 65266 ncbi.nlm.nih.gov/gene/65266 |
| Ensembl ID | ENSG00000126562 |
| UniProt ID | Q96J92 |
| OMIM ID | 601844 |
| HGNC ID | 14544 |
| Aliases | PRKWNK4, DKFZp686K05184 |
Description
WNK4 encodes a serine/threonine protein kinase belonging to the WNK (With No lysine (K)) family. The protein regulates ion transport by phosphorylating and modulating the activity of cation-chloride cotransporters, including NCC and NKCC2. Mutations in WNK4 cause pseudohypoaldosteronism type II (PHAII), a disorder characterized by hypertension and hyperkalemia.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Pseudohypoaldosteronism type II (PHAII) | Gain-of-function mutations increase NCC activity, leading to salt retention and hypertension. | OMIM #145260; ClinVar |
| Hypertension | WNK4 variants alter renal sodium handling and blood pressure regulation. | NCBI Gene; OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | Medium |
| Testis | 4.2 | Low |
| Colon | 3.1 | Low |
| Liver | 1.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 8.7 | RNA-seq data |
| HepG2 | 2.1 | Low expression |
| K-562 | 1.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.494G>A (p.Arg165Gln) | Missense | Rare | Gain-of-function; associated with PHAII |
| c.1465C>T (p.Arg489Trp) | Missense | Rare | Gain-of-function; associated with PHAII |
| c.1588G>A (p.Glu530Lys) | Missense | Rare | Gain-of-function; associated with PHAII |
Mutation functional classification
Loss of Function (LOF)
Not commonly reported for WNK4; most pathogenic mutations are gain-of-function.
Gain of Function (GOF)
Missense mutations in the acidic motif (e.g., p.Glu530Lys) increase NCC phosphorylation and activity, causing PHAII.
Dominant Negative (DN)
Not described for WNK4.
View complete mutation data：
Gene Ontology (GO)
| • protein serine/threonine kinase activity | • ATP binding |
| • ion transport | • regulation of sodium ion transport |
| • intracellular signal transduction |
Pathways
• WNK regulation of ion transport
• Aldosterone-regulated sodium reabsorption
• Sodium/chloride cotransporter activation
Protein Summary
WNK4 is a 1,222-amino acid serine/threonine kinase with a catalytic domain lacking the canonical lysine residue. It localizes to the distal nephron and regulates ion homeostasis by phosphorylating SPAK/OSR1 kinases, which in turn activate NCC. Mutations disrupt this regulation, leading to hypertension and electrolyte abnormalities.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| WNK4 Knockout HEK293 Cell Line | EDJ-KQ16148 | Human | 65266 | Details Get a Quote |
| WNK4 Knockout HCT 116 Cell Line | EDJ-KQ46107 | Human | 65266 | Details Get a Quote |
| WNK4 Knockout HeLa Cell Line | EDJ-KQ57108 | Human | 65266 | Details Get a Quote |
| WNK4 Knockout A-549 Cell Line | EDJ-KQ65623 | Human | 65266 | Details Get a Quote |
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