{"entity":{"id":"tsc2","kind":"target","name":"TSC2","aka":["TSC complex subunit 2","Tuberin","tuberin","PPP1R160","TSC4"],"tldr":"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.","summary":"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.\n\nCIViC 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).","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:12363","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:12363"},{"label":"UniProt P49815","url":"https://www.uniprot.org/uniprotkb/P49815/entry"},{"label":"NCBI Gene 7249","url":"https://www.ncbi.nlm.nih.gov/gene/7249"},{"label":"Ensembl ENSG00000103197","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000103197"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["hcc","rcc","thyroid","neuroendocrine","urothelial","esophageal","pancreatic","gastric"],"sections":[],"technologies":[],"targets":[],"drugs":["sirolimus-albumin-bound"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05103358"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: CIViC lists 2 therapies; IntOGen calls it an activating (Act) driver in 6 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 8 cohorts; CIViC holds 5 clinical evidence items on its variants. Evidence tier \"approved-drug\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate.","Diseases the sources name that have no OnCo cancer page yet, so they are not linked: Tuberous Sclerosis."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"TSC2","role":["drug-target","oncogene-driver","tumour-suppressor","biomarker"],"evidenceTier":"approved-drug","sources":[{"label":"HGNC HGNC:12363","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:12363","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P49815","url":"https://www.uniprot.org/uniprotkb/P49815/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene TSC2","url":"https://civicdb.org/features/47","note":"5 evidence items, 0 assertions, 4 variants; diseases: Tuberous Sclerosis, Thyroid Gland Carcinoma, Renal Cell Carcinoma (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000103197","url":"https://platform.opentargets.org/target/ENSG00000103197/associations","note":"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)"},{"label":"IntOGen TSC2","url":"https://www.intogen.org/search?gene=TSC2","note":"driver in 15 cohorts (Act 6, LoF 8); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"hgnc":"HGNC:12363","ensembl":"ENSG00000103197","uniprot":"P49815","entrez":"7249","biology":"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).","whereFound":["Hepatocellular carcinoma: Open Targets association 0.60 with hepatocellular carcinoma (MONDO_0007256); IntOGen driver in 5 cohorts (HCC)","Renal cell carcinoma: Open Targets association 0.57 with renal cell carcinoma (MONDO_0005086); CIViC evidence names this disease","Thyroid cancer: CIViC evidence names this disease","Neuroendocrine tumours: Open Targets association 0.57 with neuroendocrine neoplasm (MONDO_0019496); IntOGen driver in 1 cohort (PANET)","Bladder & urothelial cancer: IntOGen driver in 1 cohort (BLCA)","Oesophageal cancer: IntOGen driver in 1 cohort (ESCA)"],"targetClass":"tumor-suppressor","prevalence":[]},"route":"/targets/tsc2/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"hcc","kind":"cancer","name":"Hepatocellular carcinoma","route":"/cancers/hcc/"},{"id":"neuroendocrine","kind":"cancer","name":"Neuroendocrine tumours","route":"/cancers/neuroendocrine/"},{"id":"esophageal","kind":"cancer","name":"Oesophageal cancer","route":"/cancers/esophageal/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"},{"id":"thyroid","kind":"cancer","name":"Thyroid cancer","route":"/cancers/thyroid/"}],"drug":[{"id":"sirolimus-albumin-bound","kind":"drug","name":"Sirolimus protein-bound particles","route":"/drugs/sirolimus-albumin-bound/"}],"trial":[{"id":"nct05103358","kind":"trial","name":"Phase 2 Basket Trial of Nab-sirolimus in Patients With Malignant Solid Tumors With Pathogenic Alterations in TSC1/TSC2 Genes (PRECISION 1)","route":"/trials/nct05103358/"}]}}