STK39: Serine/Threonine Kinase 39 (SPAK)
A key regulator of ion transport, blood pressure, and cellular stress responses.
Gene Information Card
| Symbol | STK39 |
|---|---|
| Full Name | Serine/Threonine Kinase 39 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q24.3 |
| NCBI Gene ID | 27347 ncbi.nlm.nih.gov/gene/27347 |
| Ensembl ID | ENSG00000101210 |
| UniProt ID | Q9UEW8 |
| OMIM ID | 607648 |
| HGNC ID | 17717 |
| Aliases | SPAK, DCHT, PASK |
Description
STK39 (serine/threonine kinase 39), also known as SPAK (Ste20-related proline-alanine-rich kinase), encodes a member of the STE20/SPS1 family of kinases. It acts downstream of WNK kinases to phosphorylate and regulate cation-chloride cotransporters (e.g., NKCC1, NKCC2, NCC), thereby playing a critical role in ion homeostasis, blood pressure regulation, and cell volume control. STK39 is also implicated in cellular stress responses and cancer progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hypertension (essential) | STK39 variants (e.g., rs3754777) alter gene expression, affecting renal sodium reabsorption via NCC/NKCC2 phosphorylation, leading to increased blood pressure. | GWAS studies (PMID: 19430483); ClinVar association |
| Pseudohypoaldosteronism type II (PHAII) | Gain-of-function mutations in STK39 or upstream WNK kinases cause constitutive activation of NCC, resulting in hypertension and hyperkalemia. | OMIM #145260; functional studies (PMID: 17210641) |
| Colorectal cancer | STK39 overexpression promotes cell migration and invasion via activation of the p38 MAPK pathway. | COSMIC; PMID: 25605242 |
| Breast cancer | STK39 is upregulated and correlates with poor prognosis; it modulates estrogen receptor signaling and cell proliferation. | COSMIC; PMID: 29367642 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | Medium |
| Brain | 8.3 | Medium |
| Lung | 6.1 | Low |
| Colon | 5.4 | Low |
| Breast | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression |
| MCF7 | 7.8 | Medium expression |
| HCT116 | 6.5 | Medium expression |
| A549 | 5.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs3754777 (promoter) | SNP | ~20% (European) | Increased STK39 expression; associated with hypertension |
| p.Arg307Gln | Missense | <0.1% | Impaired kinase activity; reduced NCC phosphorylation |
| p.Thr233Ala | Missense | <0.1% | Altered ATP binding; loss-of-function |
Mutation functional classification
Loss of Function (LOF)
p.Arg307Gln, p.Thr233Ala – reduced kinase activity and NCC phosphorylation.
Gain of Function (GOF)
Constitutive activation via upstream WNK mutations (not directly in STK39 but in pathway); overexpression in cancers.
Dominant Negative (DN)
Not reported for STK39.
View complete mutation data：
Gene Ontology (GO)
| • protein serine/threonine kinase activity | • ATP binding |
| • ion transmembrane transport | • regulation of blood pressure |
| • cell volume homeostasis | • signal transduction |
| • protein phosphorylation |
Pathways
• WNK-SPAK/OSR1 signaling pathway
• Ion transport by Na+-K+-Cl- cotransporters
• p38 MAPK signaling
• Regulation of cell volume
Protein Summary
STK39 (SPAK) is a 556-amino acid serine/threonine kinase with an N-terminal catalytic domain and a C-terminal regulatory domain containing a PASK (proline-alanine-rich Ste20-related kinase) domain. It is activated by WNK kinases via phosphorylation at Ser373. Active STK39 phosphorylates cation-chloride cotransporters (NKCC1, NKCC2, NCC) at key threonine residues, regulating their membrane trafficking and activity. The protein is widely expressed, with highest levels in kidney and brain. Dysregulation contributes to hypertension, electrolyte disorders, and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| STK39 Knockout HEK293 Cell Line | EDJ-KQ8771 | Human | 27347 | Details Get a Quote |
| STK39 Knockout HCT 116 Cell Line | EDJ-KQ35039 | Human | 27347 | Details Get a Quote |
| STK39 Knockout HeLa Cell Line | EDJ-KQ35040 | Human | 27347 | Details Get a Quote |
| STK39 Knockout A-549 Cell Line | EDJ-KQ33782 | Human | 27347 | Details Get a Quote |
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