This study identifies proteins from the postsynaptic density (PSD) of human neocortex and finds that the PSD shows enrichment of genes involved in cognitive and affective phenotypes and that PSD mutations are associated with neurological and psychiatric disease. We isolated the postsynaptic density from human neocortex (hPSD) and identified 1,461 proteins. hPSD mutations cause 133 neurological and psychiatric diseases and were enriched in cognitive, affective and motor phenotypes underpinned by sets of genes. Strong protein sequence conservation in mammalian lineages, particularly in hub proteins, indicates conserved function and organization in primate and rodent models. The hPSD is an important structure for nervous system disease and behavior.

Characterization of the proteome, diseases and evolution of the human postsynaptic density