# TSC2

Source: https://onco.cc/targets/tsc2/  
OnCo record `tsc2` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

CIViC 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).

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: TSC complex subunit 2; Tuberin; tuberin; PPP1R160; TSC4
- Tags: cancer-genes-wave
- Symbol: TSC2
- Class: tumor-suppressor
- 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).
- Where found: 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)

## 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.

## Sources

- HGNC HGNC:12363: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:12363
- UniProt P49815: https://www.uniprot.org/uniprotkb/P49815/entry
- NCBI Gene 7249: https://www.ncbi.nlm.nih.gov/gene/7249
- Ensembl ENSG00000103197: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000103197

## 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/), [Gastric & gastro-oesophageal junction cancer](https://onco.cc/cancers/gastric/), [Hepatocellular carcinoma](https://onco.cc/cancers/hcc/), [Neuroendocrine tumours](https://onco.cc/cancers/neuroendocrine/), [Oesophageal cancer](https://onco.cc/cancers/esophageal/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Renal cell carcinoma](https://onco.cc/cancers/rcc/), [Thyroid cancer](https://onco.cc/cancers/thyroid/)
- drugs: [Sirolimus protein-bound particles](https://onco.cc/drugs/sirolimus-albumin-bound/)
- 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/tsc2.json