The Role of SHANK3 /PROSAP2 in the Pathophysiology of Autism Spectrum Disorder and Phelan–Mcdermid Syndrome

Abstract Phelan–McDermid syndrome (PMS) is a rare genetic disorder caused by a deletion or mutations of the SHANK3/ PROSAP2 gene, located on the terminal end of chromosome 22. The SHANK3/PROSAP2 gene produces a protein called SHANK3 , which is crucial for the development and function of synapses in the brain. Loss or dysfunction of SHANK3/ PROSAP2 leads to disruptions in synaptic function and plasticity. Individuals with PMS often experience developmental delay, intellectual disability and symptoms of autism spectrum disorder (ASD), including impaired communication and social interaction, repetitive behaviours and restricted interests. This review explores the role of SHANK3/ PROSAP2 in the pathogenesis of PMS and ASD, which may contribute to the cognitive and behavioural deficits seen in affected individuals. However, recent advances in understanding the underlying molecular and cellular mechanisms of PMS have led to the development of potential therapeutic targets, such as drugs that enhance synaptic function and behavioural therapies that target social communication and adaptive skills. Further research is needed to better understand the complex molecular and cellular mechanisms underlying PMS and ASD, and to develop effective treatments for these disorders. Key Concepts SHANK3/ PROSAP2 gene produces a synaptic protein whose mutation causes both in autism and philanthropy McDermid syndrome. SHANK3/ PROSAP2 is involved in synaptic transmission and functional connectivity. Recently developed mutant monkeys for SHANK3/ PROSAP2 may open invaluable insight into research of autism spectrum disorder and Phelan McDermid syndrome.