TSC1
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.
Overview
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).
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
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.
- 3 · How drugs use it
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).
External identifiers
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)
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).
- 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)
Notes
top- 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.
Latest papers
topQuery 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.
Similar pages
not linked directly; found by shared links- TargetTSC2
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.
- TrialInetetamab Plus Rapamycin and Chemotherapy for HER2+ Metastatic Breast Cancer With Abnormal Activation of PAM Pathway
Shares Sirolimus protein-bound particles, Breast cancer (all types).
- TreatmentTemsirolimus
Shares Sirolimus protein-bound particles, PI3K / AKT / mTOR, Renal cell carcinoma.
- CancerPerivascular epithelioid cell tumour (PEComa)
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.
- TermMetabolic syndrome and insulin resistance
Shares PI3K / AKT / mTOR, Hepatocellular carcinoma, Colorectal cancer.
- TargetmTOR
Shares Sirolimus protein-bound particles, PI3K / AKT / mTOR, Renal cell carcinoma.
- PathwayFGF / FGFR signalling
Shares PI3K / AKT / mTOR, Bladder & urothelial cancer, Gastric & gastro-oesophageal junction cancer.
- TechnologyFasting and fasting-mimicking diets around chemotherapy
Shares PI3K / AKT / mTOR, Colorectal cancer.