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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.
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.
CIViC 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).
In plain words · 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.
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.
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.
No product in this corpus aims at TSC1 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 TSC1: RNA low tissue specificity; high antibody staining in 6 normal tissues; highest cancer staining head and neck cancer (1 of 4 high). Distribution: 8 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Bladder & urothelial cancer, Hepatocellular carcinoma, Renal cell carcinoma, Skin cancer (all types), Colorectal cancer, Breast cancer (all types), Gastric & gastro-oesophageal junction cancer and more); approvals of single-target medicines aimed at it also list Sarcomas (soft tissue, bone, GIST), not counted; Open Targets associates it with 6 specific cancer types at or above 0.5 (tuberous sclerosis, tuberous sclerosis 1, lymphangioleiomyomatosis, urinary bladder cancer, urinary bladder carcinoma, hereditary neoplastic syndrome). (Rule 7 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas TSC1 tissue; Open Targets ENSG00000165699 associations
First described 1996. Earliest sequence paper UniProt cites for the protein: Nagase et al, DNA Res, 1996, "Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain". Source.
Sources: HGNC HGNC:12362 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q92574 (protein name, function text, keywords and locations (REST API)); CIViC gene TSC1 (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)); Open Targets ENSG00000165699 (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)); IntOGen TSC1 (driver in 14 cohorts (Act 0, LoF 13); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
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).
RNA: low tissue specificity, detected in all normal tissues.
Medium: Adrenal gland, Appendix, Breast, Bronchus, Caudate, Cerebral cortex, Cervix, Colon.
Medium only: breast cancer, carcinoid, cervical cancer, colorectal cancer.
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:"TSC1" OR ABSTRACT:"TSC1" OR TITLE:"TSC complex subunit 1" OR ABSTRACT:"TSC complex subunit 1" OR TITLE:"Hamartin" OR ABSTRACT:"Hamartin" OR TITLE:"KIAA0243" OR ABSTRACT:"KIAA0243" OR TITLE:"hamartin" OR ABSTRACT:"hamartin") 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 TSC1, 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 PI3K / AKT / mTOR, CIViC, IntOGen, Breast cancer (all types).
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.
Shares PI3K / AKT / mTOR, CIViC, IntOGen, Open Targets Platform.
Shares PI3K / AKT / mTOR, CIViC, Open Targets Platform, Non-small-cell lung cancer.
Shares PI3K / AKT / mTOR, Gastric & gastro-oesophageal junction cancer, Breast cancer (all types).
Shares Sirolimus protein-bound particles, Breast cancer (all types).
Shares Sirolimus protein-bound particles, PI3K / AKT / mTOR, Renal cell carcinoma.