Fig. 1

Proteins known to cause monogenic ASD are shown in red. Some of these, including TSC1/2, directly impact on ribosomal translation via the AKT-mTORC1 (mechanistic target of rapamycin complex 1) pathway, leading to altered synaptic protein expression and hence altered synaptic function. Others feed into this loop at the level of transcript production (MECP2 [125]) and selection (FMRP [123]) and protein degradation (UBE3A [128], not shown). Many other ASD-linked proteins also act within this synaptopathic loop, including various cell adhesion molecules (e.g. neuroligins [NLGNs], neurexins [NRXNs] [129, 130]), scaffolding proteins (e.g. postsynaptic density protein 95 [PSD95] [131]), cytoskeletal proteins (e.g. disrupted in schizophrenia 1 [DISC1] [132]), receptors (e.g. AMPA, NMDA, mGluR [133, 134]) and DNA-binding proteins (e.g. chromodomain-helicase-DNA-binding protein 8 [CHD8] [135, 136]). The entire rapidly expanding list of over 900 ASD-linked genes can be found at the Simons Foundation Autism Research Initiative (SFARI) database (https://gene.sfari.org/database/human-gene/)