SGK1 Gene - Serum/Gluocorticoid Regulated Kinase 1 | Function, Mutations & Disease

SGK1 encodes a serine/threonine protein kinase that is transcriptionally regulated by serum and glucocorticoids. It plays a critical role in cellular stress response, ion transport (especially sodium and potassium), cell proliferation, and survival. SGK1 is activated by PI3K and mTOR signaling and phosphorylates multiple targets including NDRG1, FOXO3, and MDM2. Dysregulation of SGK1 is implicated in hypertension, diabetic nephropathy, cancer, and inflammatory disorders.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• PI3K-Akt signaling pathway (KEGG: hsa04151)

• mTOR signaling pathway (KEGG: hsa04150)

• Aldosterone-regulated sodium reabsorption (KEGG: hsa04960)

• FoxO signaling pathway (KEGG: hsa04068)

SGK1 is a 431-amino acid protein kinase with a catalytic domain similar to Akt/PKB. It contains an N-terminal regulatory domain and a C-terminal hydrophobic motif. SGK1 is activated by phosphorylation at Thr256 and Ser422 via PDK1 and mTORC2. It localizes to the cytoplasm and nucleus, and its activity is rapidly induced by various stimuli including glucocorticoids, serum, and osmotic stress. The protein regulates ion channels (ENaC, Kv1.3), transcription factors (FOXO3, NF-κB), and cell cycle regulators (p27, MDM2).