# TSC1

Source: https://onco.cc/targets/tsc1/  
OnCo record `tsc1` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

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).

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: TSC complex subunit 1; Hamartin; KIAA0243; hamartin
- Tags: cancer-genes-wave
- Symbol: TSC1
- Class: tumor-suppressor
- 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).
- Where found: 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

- 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.

## Sources

- HGNC HGNC:12362: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:12362
- UniProt Q92574: https://www.uniprot.org/uniprotkb/Q92574/entry
- NCBI Gene 7248: https://www.ncbi.nlm.nih.gov/gene/7248
- Ensembl ENSG00000165699: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000165699

## Connected records

- collections: [CIViC](https://onco.cc/collections/civic/), [IntOGen](https://onco.cc/collections/intogen/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Bladder & urothelial cancer](https://onco.cc/cancers/urothelial/), [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Gastric & gastro-oesophageal junction cancer](https://onco.cc/cancers/gastric/), [Hepatocellular carcinoma](https://onco.cc/cancers/hcc/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Renal cell carcinoma](https://onco.cc/cancers/rcc/), [Skin cancer (all types)](https://onco.cc/cancers/skin-cancer/)
- drugs: [Sirolimus protein-bound particles](https://onco.cc/drugs/sirolimus-albumin-bound/)
- pathways: [PI3K / AKT / mTOR](https://onco.cc/pathways/pi3k-akt-mtor/)
- trials: [Phase 2 Basket Trial of Nab-sirolimus in Patients With Malignant Solid Tumors With Pathogenic Alterations in TSC1/TSC2 Genes (PRECISION 1)](https://onco.cc/trials/nct05103358/)

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JSON: https://onco.cc/api/v1/entities/tsc1.json