OncoSignal
Live from Open Targets Platform, fetched 2026-11-12 04:45 UTC. Every row links to its source record.

TSC2 TSC complex subunit 2

ENSG00000103197 · protein coding · Open Targets profile

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 (PubMed:12172553, PubMed:12271141, PubMed:12842888, PubMed:12906785, PubMed:15340059, PubMed:22819219, PubMed:24529379, PubMed:28215400, PubMed:33436626, PubMed:35772404). 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 (PubMed:12172553, PubMed:12820960, PubMed:12842888, PubMed:12906785, PubMed:15340059, PubMed:22819219, PubMed:24529379, PubMed:33436626). 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 signaling (PubMed:12172553, PubMed:12271141, PubMed:12842888, PubMed:12906785, PubMed:22819219, PubMed:24529379, PubMed:28215400, PubMed:35772404). The TSC-TBC complex is inactivated in response to nutrients, relieving inhibition of mTORC1 (PubMed:12172553, PubMed:24529379). Involved in microtubule-mediated protein transport via its ability to regulate mTORC1 signaling (By similarity). Also stimulates the intrinsic GTPase activity of the Ras- related proteins RAP1A and RAB5 (By similarity). {ECO:0000250|UniProtKB:P49816, ECO:0000269|PubMed:12172553, ECO:0000269|PubMed:12271141, ECO:0000269|PubMed:12820960, ECO:0000269|PubMed:12842888, ECO:0000269|PubMed:12906785, ECO:0000269|PubMed:15340059, ECO:0000269|PubMed:22819219, ECO:0000269|PubMed:24529379, ECO:0000269|PubMed:28215400, ECO:0000269|PubMed:33436626, ECO:0000269|PubMed:35772404}.

In 9 of 15 cancers, the evidence for TSC2 comes mainly from inherited variants

Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.

Inherited (germline) variantsMutations in tumours (somatic)
00.250.50.751tuberous sclerosistuberous sclerosistuberous sclerosis: germline 0.95tuberous sclerosis 2tuberous sclerosis 2tuberous sclerosis 2: somatic 0.88tuberous sclerosis 2: germline 0.95lymphangioleiomyomatosislymphangioleiomyomatosislymphangioleiomyomatosis: somatic 0.63lymphangioleiomyomatosis: germline 0.88hepatocellular carcinomahepatocellular carcinomahepatocellular carcinoma: somatic 0.76hereditary neoplastic syndromehereditary neoplastic syndromehereditary neoplastic syndrome: germline 0.94attenuated familial adenomatous polypos…attenuated familial adenomatous polyposisattenuated familial adenomatous polyposis: germline 0.90familial adenomatous polyposis 3familial adenomatous polyposis 3familial adenomatous polyposis 3: germline 0.90tuberous sclerosis 1tuberous sclerosis 1tuberous sclerosis 1: germline 0.83Cortical tubersCortical tubersCortical tubers: germline 0.72lung lymphangioleiomyomatosislung lymphangioleiomyomatosislung lymphangioleiomyomatosis: somatic 0.61lung lymphangioleiomyomatosis: germline 0.20non-small cell lung carcinomanon-small cell lung carcinomanon-small cell lung carcinoma: somatic 0.61ovarian cancerovarian cancerovarian cancer: germline 0.62neoplasm with perivascular epithelioid …neoplasm with perivascular epithelioid cell differentiationneoplasm with perivascular epithelioid cell differentiation: somatic 0.61kidney angiomyolipomakidney angiomyolipomakidney angiomyolipoma: somatic 0.61prostate carcinomaprostate carcinomaprostate carcinoma: somatic 0.61

Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.

Tractability

Antibody
UniProt loc high conf
PROTAC
UniProt Ubiquitination, Database Ubiquitination, Half-life Data

gnomAD loss of function constraint: o/e 0.14340999722480774 (upper bound 0.1955299973487854). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.

Who runs trials of these drugs

No named investigators on registry trials of TSC2's approved or late-stage drugs in the last three years.

No terminated, withdrawn or suspended trials of TSC2's drugs are registered

All 0 drugs and clinical candidates as a table

Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.

DrugTypeHighest stageIndicationsSource records
No drugs or clinical candidates recorded.