FIGURE 2: Upstream mTOR regulation and associated mutations causing mTORpathies. The TSC1/TSC2 complex, FMRP, PTEN and NF1 are negative regulators of mTORC1. Loss of function-mutations in these genes lead to an increased mTORC1 activity and a reduced autophagy induction and produce a subset of neurodevelopmental disorders known as mTORopathies. TSC1/2: Tuberous sclerosis complex 1/2, FMRP: Fragile X mental retardation protein, PTEN: Phosphatase and tensin homolog deleted on chromosome ten and NF1: Neurofibromatosis type 1.