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TSC2 (Tuberin) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and an approved or late-stage drug is recorded against it. Tied to Hepatocellular carcinoma, Renal cell carcinoma, Thyroid cancer and 5 more.
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).
In plain words · TSC2 (Tuberin) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and an approved or late-stage drug is recorded against it. Tied to Hepatocellular carcinoma, Renal cell carcinoma, Thyroid cancer and 5 more.
TSC2 (Tuberin) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and an approved or late-stage drug is recorded against it. Tied to Hepatocellular carcinoma, Renal cell carcinoma, Thyroid cancer and 5 more.
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.
No product in this corpus aims at TSC2 yet. Because the protein is lost rather than overactive, drugs either restore its function or exploit the weakness its loss leaves (synthetic lethality).
Broadly expressed or essential: HPA finds the RNA at low tissue specificity; the 1 medicine aimed at it (Sirolimus protein-bound particles) act on the wild-type protein, so normal tissue is exposed and the therapeutic window comes from the tumour's faster division or its dependence on the protein. HPA TSC2: RNA low tissue specificity; no normal tissue stained high; highest cancer staining liver cancer (6 of 12 high). Distribution: 8 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Hepatocellular carcinoma, Renal cell carcinoma, Thyroid cancer, Neuroendocrine tumours, Bladder & urothelial cancer, Oesophageal cancer, Pancreatic ductal adenocarcinoma and more); approvals of single-target medicines aimed at it also list Sarcomas (soft tissue, bone, GIST), not counted; Open Targets associates it with 8 specific cancer types at or above 0.5 (tuberous sclerosis, tuberous sclerosis 2, lymphangioleiomyomatosis, hepatocellular carcinoma, hereditary neoplastic syndrome, familial adenomatous polyposis 3 and more). (Rule 7 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas TSC2 tissue; Open Targets ENSG00000103197 associations
First described 1993. Earliest sequence paper UniProt cites for the protein: Nellist et al, Cell, 1993, "Identification and characterization of the tuberous sclerosis gene on chromosome 16". Source.
Sources: HGNC HGNC:12363 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P49815 (protein name, function text, keywords and locations (REST API)); CIViC gene TSC2 (5 evidence items, 0 assertions, 4 variants; diseases: Tuberous Sclerosis, Thyroid Gland Carcinoma, Renal Cell Carcinoma (GraphQL API, CC0)); Open Targets ENSG00000103197 (association with cancer (MONDO_0004992) 0.80; per-cancer scores at or above 0.5: non-small cell lung carcinoma 0.53, colorectal cancer 0.54, hepatocellular carcinoma 0.60, renal cell carcinoma 0.57, ovarian cancer 0.51, melanoma 0.57 (GraphQL API, CC0)); IntOGen TSC2 (driver in 15 cohorts (Act 6, LoF 8); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
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. The TSC-TBC complex is inactivated in response to nutrients, relieving inhibition of mTORC1. Involved in microtubule-mediated protein transport via its ability to regulate mTORC1 signalling. Also stimulates the intrinsic GTPase activity of the Ras-related proteins RAP1A and RAB5. Location: Lysosome membrane; Cytoplasm, cytosol (UniProt). Locus 16p13.3 (HGNC).
RNA: low tissue specificity, detected in all normal tissues.
No normal tissue stained high; medium in Adrenal gland, Caudate, Cerebellum, Cerebral cortex, Colon, Duodenum and more.
Medium only: colorectal cancer, endometrial cancer, lung cancer, melanoma.
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
Query for this target: (TITLE:"TSC2" OR ABSTRACT:"TSC2" OR TITLE:"TSC complex subunit 2" OR ABSTRACT:"TSC complex subunit 2" OR TITLE:"Tuberin" OR ABSTRACT:"Tuberin" OR TITLE:"tuberin" OR ABSTRACT:"tuberin" OR TITLE:"PPP1R160" OR ABSTRACT:"PPP1R160" OR TITLE:"TSC4" OR ABSTRACT:"TSC4") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about TSC2, not a curated reading list.
Shares Phase 2 Basket Trial of Nab-sirolimus in Patients With Malignant Solid Tumors With Pathogenic Alterations in TSC1/TSC2 Genes (PRECISION 1), Sirolimus protein-bound particles, Renal cell carcinoma, Bladder & urothelial cancer.
Shares Thyroid cancer, Neuroendocrine tumours, Oesophageal cancer, IntOGen.
Shares Thyroid cancer, Renal cell carcinoma, Bladder & urothelial cancer, CIViC.
Shares Thyroid cancer, Neuroendocrine tumours, Hepatocellular carcinoma, IntOGen.
Shares Thyroid cancer, Neuroendocrine tumours, Hepatocellular carcinoma, CIViC.
Shares Thyroid cancer, Renal cell carcinoma, CIViC, IntOGen.
Shares Thyroid cancer, Neuroendocrine tumours, Bladder & urothelial cancer, CIViC.
Shares Thyroid cancer, Neuroendocrine tumours, CIViC, Open Targets Platform.