The human TSC1 gene has been identified as a candidate susceptibility locus for autism spectrum disorder (FBhh0000514). TSC1 (tuberous sclerosis 1) acts in a complex with TSC2 and has a role in the regulation of cell growth and proliferation. There is a single orthologous gene in Drosophila, Dmel\Tsc1, for which loss-of-function alleles, RNAi targeting constructs, and alleles caused by insertional mutagenesis have been generated. TSC1 has also been implicated in tuberous sclerosis 1 (FBhh0000224, MIM:191100) and Lymphangioleiomyomatosis (MIM:606690).
The human TSC1 gene has not been introduced into flies.
Animals homozygous for loss-of-function alleles of Dmel\Tsc1 die before the end of larval stage. Effects upon cell growth have been assayed using somatic clones. RNAi-effected loss of function leads to reduced behavioral flexibility as shown by severe reversal-learning impairment; it is postulated that this phenotype results from the failure to properly activate Rac1-dependent forgetting. Extensive genetic and physical interactions for Dmel\Tsc1 have been described; see below and in the gene report for Tsc1.
[updated Mar. 2017 by FlyBase; FBrf0222196]
Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic, and ritualized patterns of interests and behavior (Bailey et al., 1996, pubmed:8655659; Risch et al., 1999, pubmed:10417292). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (MIM:608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008; pubmed:18698615). [from MIM:209850; 2017.03.18]
The SFARI Gene autism database ( https:gene.sfari.org ) rates the gene-autism association for TSC1 as high confidence (score 1). [2020.11.05]
In a complex with TSC2, TSC1 inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling. [from Gene Cards, TSC1; 2017.03.20]
One to one (1 human to 1 Drosophila).
High-scoring ortholog of human TSC1 (1 Drosophila to 1 human); Dmel\Tsc1 shares 23% identity and 40% similarity with the human gene.
