TSC1
Chr 9ADTSC complex subunit 1
Also known as: LAM, TSC
This gene is a tumor suppressor gene that encodes the growth inhibitory protein hamartin. The encoded protein interacts with and stabilizes the GTPase activating protein tuberin. This hamartin-tuberin complex negatively regulates mammalian target of rapamycin complex 1 (mTORC1) signaling which is a major regulator of anabolic cell growth. This protein also functions as a co-chaperone for Hsp90 that inhibits its ATPase activity. This protein functions as a facilitator of Hsp90-mediated folding of kinase and non-kinase clients, including TSC2 and thereby preventing their ubiquitination and proteasomal degradation. Mutations in this gene have been associated with tuberous sclerosis and lymphangioleiomyomatosis. [provided by RefSeq, May 2022]
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Moderately missense-constrained (top ~2.5%)
ClinVar Variant Classifications
5711 submitted variants in ClinVar
Classification Summary
Protein Context — Lollipop Plot
TSC1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
Gene2Phenotype Curations
TSC1-related tuberous sclerosis
definitiveGene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org
OMIM — Genotype-Phenotype Relationships
2 OMIM entries
External Resources
Links to major genomics databases and tools
Variant Interpretation
Population Databases
Gene Resources
Expert Curation
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Testing the Addition of Ipatasertib to the Usual Chemotherapy Treatment (Paclitaxel and Carboplatin) for Stage III or IV Epithelial Ovarian Cancer
ACTIVE NOT RECRUITINGPhase 2 Basket Trial of Nab-sirolimus in Patients With Malignant Solid Tumors With Pathogenic Alterations in TSC1/TSC2 Genes (PRECISION 1)
ACTIVE NOT RECRUITINGCanadian Profiling and Targeted Agent Utilization Trial (CAPTUR)
RECRUITINGPrevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History
NOT YET RECRUITINGTesting the Addition of an Anti-cancer Drug, Sapanisertib, to the Usual Chemotherapy Treatment (Cabozantinib) in Metastatic Liver Cell Cancer With a Change in Genes for the Protein β-Catenin, The SAPHIRE Trial
RECRUITINGPrecision Medicine in the Treatment of Epilepsy
RECRUITINGTargeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)
ACTIVE NOT RECRUITINGAdapting Treatment to the Tumor Molecular Alterations for Patients With Advanced Solid Tumors: MyOwnSpecificTreatment
RECRUITINGTargeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
ACTIVE NOT RECRUITINGTAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer
RECRUITINGThe CATALINA Study
RECRUITINGExternal Resources
Links to major genomics databases and tools