WNK1
WNK Lysine Deficient Protein Kinase 1
Gene Information Card
| Symbol | WNK1 |
|---|---|
| Full Name | WNK lysine deficient protein kinase 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 12p13.33 |
| NCBI Gene ID | 65125 ncbi.nlm.nih.gov/gene/65125 |
| Ensembl ID | ENSG00000060237 |
| UniProt ID | Q9H4A3 |
| OMIM ID | 605232 |
| HGNC ID | 14540 |
| Aliases | KDP, PRKWNK1, hWNK1 |
Description
WNK1 encodes a serine/threonine protein kinase that lacks a conserved catalytic lysine residue, characteristic of the WNK kinase family. It plays a critical role in regulating ion homeostasis, blood pressure, and neuronal signaling through modulation of ion transporters and channels.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Pseudohypoaldosteronism type 2 (PHA2) | Gain-of-function mutations in WNK1 increase activity of the Na-Cl cotransporter NCC, leading to hypertension and hyperkalemia. | OMIM #145260 |
| Hereditary sensory and autonomic neuropathy type 2A (HSAN2A) | Loss-of-function mutations disrupt axonal transport and sensory neuron survival. | OMIM #201300 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.3 | Medium |
| Testis | 8.7 | Medium |
| Brain | 6.5 | Low |
| Heart | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.1 | High expression |
| HeLa | 9.8 | Moderate expression |
| K-562 | 7.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1465C>T (p.Arg489Cys) | Missense | Rare | Gain-of-function; associated with PHA2 |
| c.2260C>T (p.Arg754*) | Nonsense | Rare | Loss-of-function; associated with HSAN2A |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations in WNK1 cause hereditary sensory neuropathy type 2A by impairing kinase activity and protein stability.
Gain of Function (GOF)
Missense mutations in the acidic motif or kinase domain enhance NCC phosphorylation, leading to pseudohypoaldosteronism type 2.
Dominant Negative (DN)
Not well documented for WNK1.
View complete mutation data：
Gene Ontology (GO)
| • protein serine/threonine kinase activity | • ion transmembrane transport |
| • regulation of blood pressure | • chloride transmembrane transport |
| • intracellular signal transduction |
Pathways
• WNK regulation of ion transport
• Aldosterone-regulated sodium reabsorption
• mTOR signaling
Protein Summary
WNK1 is a 2382-amino acid serine/threonine kinase with an N-terminal kinase domain, an autoinhibitory domain, and multiple coiled-coil regions. It phosphorylates and activates downstream kinases (OSR1, SPAK), which in turn regulate ion cotransporters (NCC, NKCC1). WNK1 is widely expressed, with highest levels in kidney, testis, and brain.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| WNK1 Knockout HAP1 Cell Line | EDC08378 | Human | 65125 | Details Get a Quote |
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