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.
Abnormalities with PSD proteins are linked to various neuropsychiatric diseases including neurodevelopmental disorders such as autism spectrum disorder and schizophrenia.
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.
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).