protein
Tuberin
Gene
TSC2
Organism
Homo sapiens(9606)
Length
1807 aa
Mass
200,608 Da
Tuberin (TSC2) is the catalytic component of the TSC-TBC complex, a multiprotein complex that negatively regulates mTORC1, a central nutrient sensor controlling anabolic reactions and cellular growth (UniProt: P49815). Within this complex, TSC2 functions as a GTPase-activating protein for RHEB, thereby inhibiting mTORC1's phosphorylation of downstream effectors like RPS6KB1/2 and EIF4EBP1 in nutrient-depleted conditions. The complex is inactivated in response to nutrient availability, allowing mTORC1 activation to proceed.
TSC2 mutations cause tuberous sclerosis 2, an autosomal dominant multi-system disorder affecting the brain, kidneys, heart, and skin, characterized by hamartomas and clinical features including epilepsy, learning difficulties, behavioral problems, and skin lesions (UniProt: P49815). TSC2 is also associated with lymphangioleiomyomatosis, a progressive lung disease primarily affecting women, and focal cortical dysplasia 2, which presents with medically refractory epilepsy and disrupted cortical organization in pediatric and adult populations.
TSC2 is classified as a syndromic autism-associated gene by SFARI (SFARI Cat S), indicating its relevance to autism within the context of tuberous sclerosis complex, where developmental and behavioral manifestations overlap with autism spectrum features.
Generated from the curated entity record below. May contain errors — verify against source links.
Genetic Evidence · ASD
Source: SFARI Gene database · gene.sfari.org
Related Publications
Browse all →Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
Ruzzo Elizabeth K et al.Cell2019PMID 31398340Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
Guo Hui et al.Molecular autism2018PMID 30564305Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
C Yuen Ryan K et al.Nature neuroscience2017PMID 28263302Identification of common genetic risk variants for autism spectrum disorder.
Grove Jakob et al.Nature genetics2019PMID 30804558Synaptic, transcriptional and chromatin genes disrupted in autism.
De Rubeis Silvia et al.Nature2014PMID 25363760
Function
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:12842888, PubMed:12906785, PubMed:15340059, PubMed:22819219, PubMed:24529379, PubMed:28215400, PubMed:33436626, PubMed:35772404). 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 (PubMed:12172553, PubMed:12820960, PubMed:12842888, PubMed:12906785, PubMed:15340059, PubMed:22819219, PubMed:24529379, PubMed:33436626). 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:12172553, PubMed:12271141, PubMed:12842888, PubMed:12906785, PubMed:22819219, PubMed:24529379, PubMed:28215400, PubMed:35772404). The TSC-TBC complex is inactivated in response to nutrients, relieving inhibition of mTORC1 (PubMed:12172553, PubMed:24529379). Involved in microtubule-mediated protein transport via its ability to regulate mTORC1 signaling (By similarity). Also stimulates the intrinsic GTPase activity of the Ras-related proteins RAP1A and RAB5 (By similarity)
Disease associations
Tuberous sclerosis 2TSC2
An autosomal dominant multi-system disorder that affects especially the brain, kidneys, heart, and skin. It is characterized by hamartomas (benign overgrowths predominantly of a cell or tissue type that occurs normally in the organ) and hamartias (developmental abnormalities of tissue combination). Clinical manifestations include epilepsy, learning difficulties, behavioral problems, and skin lesions. Seizures can be intractable and premature death can occur from a variety of disease-associated causes.
LymphangioleiomyomatosisLAM
Progressive and often fatal lung disease characterized by a diffuse proliferation of abnormal smooth muscle cells in the lungs. It affects almost exclusively young women and can occur as an isolated disorder or in association with tuberous sclerosis complex.
Focal cortical dysplasia 2FCORD2
A form of focal cortical dysplasia, a malformation of cortical development that results in medically refractory epilepsy in the pediatric population and in adults. FCORD2 is a severe form, with onset usually in childhood, characterized by disrupted cortical lamination and specific cytological abnormalities. It is classified in 2 subtypes: type IIA characterized by dysmorphic neurons and lack of balloon cells; type IIB with dysmorphic neurons and balloon cells.
Sources
Last updated 5/6/2026, 5:25:03 AM