This study identifies <i>CAPG</i> and <i>VDAC3</i> as candidate genes and provides additional support for genes encoding PSD proteins in ASD susceptibility.
Mutations within the <i>Shank3</i> gene, which encodes a key postsynaptic density (PSD) protein at glutamatergic synapses, contribute to the genetic etiology of defined autism spectrum disorders (ASDs), including Phelan-McDermid syndrome (PMS) and intellectual disabilities (ID).
The <i>SHANK3</i> gene (and to a lesser degree <i>SHANK2</i>) which encode for the postsynaptic density (PSD) proteins SHANK3/SHANK2 and the <i>CONTACTIN 4</i> gene which encodes for the neuronal glycoprotein CONTACTIN4 (CNTN4) exhibit mutated variants which are associated with ASD.
Abnormalities with PSD proteins are linked to various neuropsychiatric diseases including neurodevelopmental disorders such as autism spectrum disorder and schizophrenia.
Several PSD proteins associated with ASDs are part of a complex centered around ProSAP/Shank proteins and many ProSAP/Shank interaction partners play a role in signaling within dendritic spines.