TSC1

TSC1 is a human gene that encodes hamartin, a protein involved in regulating cell growth. The gene is located on chromosome 9 and, together with TSC2, forms a protein complex that suppresses cellular proliferation.

The hamartin-tuberin complex acts as a GTPase-activating protein for the Rheb GTPase, inhibiting the mTORC1 signaling pathway in response to growth signals and cellular energy status. This regulation helps control cell growth and proliferation in various tissues.

Mutations in TSC1 or TSC2 cause tuberous sclerosis complex (TSC), an autosomal dominant neurocutaneous disorder characterized by hamartomas in multiple organs, including cortical tubers and subependymal nodules in the brain, renal angiomyolipomas, cardiac rhabdomyomas, and various skin manifestations. Inheritance is autosomal dominant, but many cases arise from de novo mutations. TSC1 mutations are often associated with a broader range of manifestations, while TSC2 mutations are more frequently linked to more severe disease.

Management focuses on monitoring and treating affected organs. mTOR inhibitors such as everolimus can reduce the size of certain TSC-associated tumors, including renal angiomyolipomas and subependymal giant cell astrocytomas. Seizure control, neurodevelopmental support, and regular surveillance for organ involvement are important components of care, with genetic testing used for diagnosis and family counseling.