{"entity":{"id":"tsc1","kind":"target","name":"TSC1","aka":["TSC complex subunit 1","Hamartin","KIAA0243","hamartin"],"tldr":"TSC1 (Hamartin) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, a tumour suppressor and a biomarker, and an approved or late-stage drug is recorded against it. Tied to Bladder & urothelial cancer, Hepatocellular carcinoma, Renal cell carcinoma and 5 more.","summary":"Non-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. The TSC-TBC complex 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 9 clinical evidence items and 0 assertions across 4 variants, naming Everolimus, MTOR Inhibitor and Sirolimus. Open Targets scores its association with cancer at 0.81 (direct and indirect evidence; datatypes literature 0.97, affected pathway 0.89, genetic association 0.20, somatic mutation 0.95). IntOGen calls it a driver in 14 cohorts (0 activating, 13 loss-of-function), covering Bladder Urothelial Carcinoma, Invasive Breast Carcinoma, Colorectal Adenocarcinoma, Hepatocellular Carcinoma, Lung Adenocarcinoma, Renal Cell Carcinoma and others. In OnCo, 1 product record names it (Sirolimus protein-bound particles).","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:12362","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:12362"},{"label":"UniProt Q92574","url":"https://www.uniprot.org/uniprotkb/Q92574/entry"},{"label":"NCBI Gene 7248","url":"https://www.ncbi.nlm.nih.gov/gene/7248"},{"label":"Ensembl ENSG00000165699","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000165699"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["urothelial","hcc","rcc","skin-cancer","colorectal","breast-cancer","gastric","nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["sirolimus-albumin-bound"],"companies":[],"institutions":[],"pathways":["pi3k-akt-mtor"],"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 3 therapies; IntOGen calls it a loss-of-function (LoF) driver in 13 cohorts; CIViC holds 9 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; Invasive Bladder Transitional Cell Carcinoma."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"TSC1","role":["drug-target","tumour-suppressor","biomarker"],"evidenceTier":"approved-drug","sources":[{"label":"HGNC HGNC:12362","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:12362","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q92574","url":"https://www.uniprot.org/uniprotkb/Q92574/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene TSC1","url":"https://civicdb.org/features/46","note":"9 evidence items, 0 assertions, 4 variants; diseases: Tuberous Sclerosis, Renal Cell Carcinoma, Bladder Carcinoma, Lung Adenocarcinoma, Invasive Bladder Transitional Cell Carcinoma (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000165699","url":"https://platform.opentargets.org/target/ENSG00000165699/associations","note":"association with cancer (MONDO_0004992) 0.81; per-cancer scores at or above 0.5: colorectal cancer 0.53, urinary bladder cancer 0.73, renal cell carcinoma 0.57, melanoma 0.59, skin cancer 0.59 (GraphQL API, CC0)"},{"label":"IntOGen TSC1","url":"https://www.intogen.org/search?gene=TSC1","note":"driver in 14 cohorts (Act 0, LoF 13); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"hgnc":"HGNC:12362","ensembl":"ENSG00000165699","uniprot":"Q92574","entrez":"7248","biology":"Non-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. The TSC-TBC complex 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. Within the TSC-TBC complex, TSC1 stabilises TSC2 and prevents TSC2 self-aggregation. Acts as a tumour suppressor. Location: Lysosome membrane; Cytoplasm, cytosol (UniProt). Locus 9q34.13 (HGNC).","whereFound":["Bladder & urothelial cancer: Open Targets association 0.73 with urinary bladder cancer (MONDO_0001187); CIViC evidence names this disease","Hepatocellular carcinoma: IntOGen driver in 3 cohorts (HCC)","Renal cell carcinoma: Open Targets association 0.57 with renal cell carcinoma (MONDO_0005086); CIViC evidence names this disease","Skin cancer: Open Targets association 0.59 with skin cancer (MONDO_0002898)","Colorectal cancer: Open Targets association 0.53 with colorectal cancer (MONDO_0005575); IntOGen driver in 1 cohort (COADREAD)","Breast cancer: IntOGen driver in 1 cohort (BRCA)"],"targetClass":"tumor-suppressor","prevalence":[]},"route":"/targets/tsc1/","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":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"hcc","kind":"cancer","name":"Hepatocellular carcinoma","route":"/cancers/hcc/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"}],"drug":[{"id":"sirolimus-albumin-bound","kind":"drug","name":"Sirolimus protein-bound particles","route":"/drugs/sirolimus-albumin-bound/"}],"pathway":[{"id":"pi3k-akt-mtor","kind":"pathway","name":"PI3K / AKT / mTOR","route":"/pathways/pi3k-akt-mtor/"}],"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/"}]}}