SGK3: Serum/Glucocorticoid Regulated Kinase Family Member 3
A key regulator of cell survival, ion transport, and cancer progression
Gene Information Card
| Symbol | SGK3 |
|---|---|
| Full Name | Serum/Glucocorticoid Regulated Kinase Family Member 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 8q12.3 |
| NCBI Gene ID | 23678 ncbi.nlm.nih.gov/gene/23678 |
| Ensembl ID | ENSG00000104231 |
| UniProt ID | Q96BR1 |
| OMIM ID | 607589 |
| HGNC ID | 10812 |
| Aliases | SGK2, CISK, SGK-like |
Description
SGK3 (serum/glucocorticoid regulated kinase family member 3) encodes a serine/threonine protein kinase that belongs to the AGC family of kinases. It is activated by growth factors, hormones, and cellular stress via PI3K-dependent phosphorylation. SGK3 regulates cell survival, proliferation, ion transport, and glucose metabolism. It is widely expressed and has been implicated in cancer, particularly breast cancer, where it can compensate for loss of AKT signaling.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast Cancer | SGK3 overexpression promotes cell survival and proliferation via PI3K/AKT-independent activation of mTORC1 and phosphorylation of TSC2. | PMID: 21804531, COSMIC |
| Prostate Cancer | SGK3 is upregulated and associated with poor prognosis; regulates androgen receptor signaling. | PMID: 23542147 |
| Hepatocellular Carcinoma | SGK3 promotes tumor growth and metastasis through activation of the PI3K/AKT pathway. | PMID: 27626308 |
| Colorectal Cancer | SGK3 overexpression correlates with advanced stage and metastasis; regulates cell migration. | PMID: 26077642 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Breast | 12.5 | Medium |
| Prostate | 9.8 | Medium |
| Liver | 7.2 | Low |
| Colon | 6.5 | Low |
| Kidney | 15.3 | High |
| Testis | 18.1 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 14.2 | High expression |
| PC3 (prostate cancer) | 11.0 | Medium expression |
| HepG2 (liver cancer) | 8.5 | Low expression |
| HEK293 (embryonic kidney) | 16.7 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1124A>G (p.Asn375Ser) | Missense | <0.1% | Unknown functional effect; reported in COSMIC |
| c.1483C>T (p.Arg495Trp) | Missense | <0.1% | Reported in breast cancer; potential loss of function |
| c.1765G>A (p.Glu589Lys) | Missense | <0.1% | Reported in colorectal cancer; uncertain significance |
Mutation functional classification
Loss of Function (LOF)
Mutations in the kinase domain (e.g., p.Arg495Trp) may impair catalytic activity, reducing downstream signaling.
Gain of Function (GOF)
Amplification or overexpression of SGK3 is observed in cancers, leading to enhanced survival signaling.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for SGK3.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004672 - protein kinase activity | • GO:0005524 - ATP binding |
| • GO:0006468 - protein phosphorylation | • GO:0016310 - phosphorylation |
| • GO:0046777 - protein autophosphorylation | • GO:0035556 - intracellular signal transduction |
| • GO:0008284 - positive regulation of cell population proliferation | • GO:0043066 - negative regulation of apoptotic process |
Pathways
• PI3K/AKT signaling pathway (Reactome: R-HSA-1257604)
• mTORC1 signaling (Reactome: R-HSA-165159)
• Insulin signaling (Reactome: R-HSA-74752)
• Ion transport by Na+/K+ ATPase (Reactome: R-HSA-936837)
Protein Summary
SGK3 is a 496-amino acid serine/threonine kinase with an N-terminal catalytic domain and a C-terminal hydrophobic motif. It is activated by PDK1 and mTORC2 phosphorylation. SGK3 shares high homology with SGK1 and SGK2 but has distinct tissue expression and regulation. It phosphorylates substrates such as NDRG1, TSC2, and FOXO3a, influencing cell growth, survival, and metabolism. In cancer, SGK3 can substitute for AKT in PI3K-driven tumors, making it a potential therapeutic target.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| C8orf44-SGK3 Knockout HEK293 Cell Line | EDJ-KQ1525 | Human | 100533105 | Details Get a Quote |
| SGK3 Knockout HEK293 Cell Line | EDJ-KQ51127 | Human | 23678 | Details Get a Quote |
| SGK3 Knockout HeLa Cell Line | EDJ-KQ55794 | Human | 23678 | Details Get a Quote |
| C8orf44-SGK3 Knockout HeLa Cell Line | EDJ-KQ60967 | Human | 100533105 | Details Get a Quote |
| SGK3 Knockout A-549 Cell Line | EDJ-KQ64290 | Human | 23678 | Details Get a Quote |
| C8orf44-SGK3 Knockout A-549 Cell Line | EDJ-KQ69442 | Human | 100533105 | Details Get a Quote |
| SGK3 Knockout HCT 116 Cell Line | EDJ-KQ72738 | Human | 23678 | Details Get a Quote |
| C8orf44-SGK3 Knockout HCT 116 Cell Line | EDJ-KQ77793 | Human | 100533105 | Details Get a Quote |
| SGK3 Knockout HAP1 Cell Line | EDC07766 | Human | 23678 | Details Get a Quote |
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