OncoSignal
Live from Open Targets Platform, fetched 2026-11-12 00:05 UTC. Every row links to its source record.

TSC1 TSC complex subunit 1

ENSG00000165699 · protein coding · Open Targets profile

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 (PubMed:12172553, PubMed:12271141, PubMed:12906785, PubMed:15340059, PubMed:24529379, PubMed:28215400). 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 (PubMed:12906785, PubMed:15340059, PubMed:24529379). 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 signaling (PubMed:12271141, PubMed:24529379, PubMed:28215400, PubMed:33215753). The TSC-TBC complex is inactivated in response to nutrients, relieving inhibition of mTORC1 (PubMed:12172553, PubMed:24529379). Within the TSC-TBC complex, TSC1 stabilizes TSC2 and prevents TSC2 self-aggregation (PubMed:10585443, PubMed:28215400). Acts as a tumor suppressor (PubMed:9242607). Involved in microtubule- mediated protein transport via its ability to regulate mTORC1 signaling (By similarity). Also acts as a co-chaperone for HSP90AA1 facilitating HSP90AA1 chaperoning of protein clients such as kinases, TSC2 and glucocorticoid receptor NR3C1 (PubMed:29127155). Increases ATP binding to HSP90AA1 and inhibits HSP90AA1 ATPase activity (PubMed:29127155). Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed:29127155). Recruits TSC2 to HSP90AA1 and stabilizes TSC2 by preventing the interaction between TSC2 and ubiquitin ligase HERC1 (PubMed:16464865, PubMed:29127155). {ECO:0000250|UniProtKB:Q9Z136, ECO:0000269|PubMed:10585443, ECO:0000269|PubMed:12172553, ECO:0000269|PubMed:12271141, ECO:0000269|PubMed:12906785, ECO:0000269|PubMed:15340059, ECO:0000269|PubMed:16464865, ECO:0000269|PubMed:24529379, ECO:0000269|PubMed:28215400, ECO:0000269|PubMed:29127155, ECO:0000269|PubMed:33215753, ECO:0000269|PubMed:9242607}.

In 10 of 15 cancers, the evidence for TSC1 comes mainly from mutations found in tumours

Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.

Inherited (germline) variantsMutations in tumours (somatic)
00.250.50.751tuberous sclerosistuberous sclerosistuberous sclerosis: germline 0.94tuberous sclerosis 1tuberous sclerosis 1tuberous sclerosis 1: somatic 0.19tuberous sclerosis 1: germline 0.95lymphangioleiomyomatosislymphangioleiomyomatosislymphangioleiomyomatosis: germline 0.93urinary bladder cancerurinary bladder cancerurinary bladder cancer: somatic 0.83urinary bladder carcinomaurinary bladder carcinomaurinary bladder carcinoma: somatic 0.79hereditary neoplastic syndromehereditary neoplastic syndromehereditary neoplastic syndrome: germline 0.93hepatocellular carcinomahepatocellular carcinomahepatocellular carcinoma: somatic 0.52Cortical tubersCortical tubersCortical tubers: germline 0.67colorectal adenocarcinomacolorectal adenocarcinomacolorectal adenocarcinoma: somatic 0.52prostate carcinomaprostate carcinomaprostate carcinoma: somatic 0.61bladder transitional cell carcinomabladder transitional cell carcinomabladder transitional cell carcinoma: somatic 0.61subependymal giant cell astrocytomasubependymal giant cell astrocytomasubependymal giant cell astrocytoma: somatic 0.61Unclassified Renal Cell CarcinomaUnclassified Renal Cell CarcinomaUnclassified Renal Cell Carcinoma: somatic 0.61hemangioblastomahemangioblastomahemangioblastoma: somatic 0.61skin basal cell carcinomaskin basal cell carcinomaskin basal cell carcinoma: somatic 0.61

Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.

Tractability

Antibody
UniProt loc high conf, GO CC high conf
PROTAC
UniProt Ubiquitination, Database Ubiquitination, Half-life Data

gnomAD loss of function constraint: o/e 0.1609099954366684 (upper bound 0.23382000625133514). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.

Who runs trials of these drugs

No named investigators on registry trials of TSC1's approved or late-stage drugs in the last three years.

No terminated, withdrawn or suspended trials of TSC1's drugs are registered

All 0 drugs and clinical candidates as a table

Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.

DrugTypeHighest stageIndicationsSource records
No drugs or clinical candidates recorded.