TSC2

Catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth. Within the TSC-TBC complex, TSC2 acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1. In absence of nutrients, the TSC-TBC complex inhibits mTORC1, thereby preventing phosphorylation of ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1) by the mTORC1 signalling.

CIViC holds 5 clinical evidence items and 0 assertions across 4 variants, naming Everolimus and MTOR Inhibitor. Open Targets scores its association with cancer at 0.80 (direct and indirect evidence; datatypes literature 0.96, affected pathway 0.71, genetic association 0.63, somatic mutation 0.90). IntOGen calls it a driver in 15 cohorts (6 activating, 8 loss-of-function), covering Angiosarcoma, Bladder Urothelial Carcinoma, Cholangiocarcinoma, Chromophobe Renal Cell Carcinoma, Oesophageal Adenocarcinoma, Hepatocellular Carcinoma and others. In OnCo, 1 product record names it (Sirolimus protein-bound particles).