OXSR1: Oxidative Stress Responsive Kinase 1
A key regulator of ion transport and cell volume homeostasis
Gene Information Card
| Symbol | OXSR1 |
|---|---|
| Full Name | Oxidative Stress Responsive Kinase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 3p22.1 |
| NCBI Gene ID | 9943 ncbi.nlm.nih.gov/gene/9943 |
| Ensembl ID | ENSG00000172939 |
| UniProt ID | O95747 |
| OMIM ID | 601902 |
| HGNC ID | 8531 |
| Aliases | OSR1, SPAK, DKFZp686I1527 |
Description
OXSR1 (oxidative stress responsive kinase 1), also known as OSR1 or SPAK, encodes a serine/threonine kinase that acts downstream of WNK kinases to regulate ion cotransporters, particularly NKCC1, NKCC2, and NCC. It plays a critical role in cell volume regulation, blood pressure control, and ion homeostasis. The kinase is activated by osmotic stress and phosphorylates cation-chloride cotransporters to modulate their activity.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hypertension | Dysregulation of WNK-OSR1 signaling leads to altered sodium reabsorption in the kidney | PMID: 17959757 |
| Pseudohypoaldosteronism type II (PHAII) | Gain-of-function mutations in WNK kinases enhance OSR1 activity, causing hypertension and hyperkalemia | PMID: 11574891 |
| Cancer (various) | OXSR1 overexpression or mutation may promote tumor cell survival under osmotic stress | COSMIC database |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 28.5 | High |
| Brain | 15.2 | Medium |
| Lung | 12.8 | Medium |
| Heart | 10.1 | Medium |
| Liver | 6.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 22.4 | High expression |
| HeLa | 18.7 | Moderate expression |
| A549 | 14.2 | Moderate expression |
| MCF7 | 9.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1012C>T (p.Arg338Trp) | Missense | 0.01% | Unknown functional effect |
| c.1456G>A (p.Glu486Lys) | Missense | 0.005% | Potential loss of kinase activity |
| c.1742A>G (p.Asn581Ser) | Missense | 0.002% | Reported in COSMIC for colorectal cancer |
Mutation functional classification
Loss of Function (LOF)
Mutations in the kinase domain (e.g., p.Glu486Lys) may impair ATP binding or catalytic activity, reducing phosphorylation of downstream cotransporters.
Gain of Function (GOF)
Activating mutations in upstream WNK kinases (e.g., WNK1, WNK4) indirectly enhance OSR1 activity; direct gain-of-function mutations in OSR1 are rare.
Dominant Negative (DN)
Not well characterized; truncated forms lacking the kinase domain could interfere with normal signaling.
View complete mutation data：
Gene Ontology (GO)
Pathways
• WNK signaling pathway (Reactome: R-HSA-2672351)
• Ion transport by P-type ATPases (Reactome: R-HSA-936837)
• Regulation of water balance by renal aquaporins (Reactome: R-HSA-432040)
Protein Summary
OXSR1 (OSR1/SPAK) is a 527-amino acid serine/threonine kinase with an N-terminal kinase domain and a C-terminal regulatory domain. It is activated by WNK kinases via phosphorylation at Ser325 and Thr243. The active kinase phosphorylates and activates cation-chloride cotransporters (NKCC1, NKCC2, NCC), thereby regulating ion flux and cell volume. It is ubiquitously expressed with highest levels in kidney and brain. Dysregulation contributes to hypertension and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| OXSR1 Knockout HEK293 Cell Line | EDJ-KQ6833 | Human | 9943 | Details Get a Quote |
| OXSR1 Knockout HeLa Cell Line | EDJ-KQ30014 | Human | 9943 | Details Get a Quote |
| OXSR1 Knockout A-549 Cell Line | EDJ-KQ31373 | Human | 9943 | Details Get a Quote |
| OXSR1 Knockout HCT 116 Cell Line | EDJ-KQ31374 | Human | 9943 | Details Get a Quote |
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