SYNGAP1

At least 40 mutations in the SYNGAP1 gene have been found to cause SYNGAP1-related intellectual disability. In addition to mild-to-moderate intellectual disability, this condition commonly features other neurological problems, including recurrent seizures (epilepsy) and autism spectrum disorder, which affects communication and social interaction. 

Gene mutations involved in SYNGAP1-related intellectual disability prevent the production of functional SynGAP protein from one copy of the gene, reducing the protein's activity in cells. Studies show that a reduction of SynGAP activity can have multiple effects in nerve cells, including pushing synapses to develop (mature) too early. The changes triggered by a reduction of SynGAP activity disrupt the synaptic adaptations in the brain that underlie learning and memory, leading to cognitive impairment and other neurological problems characteristic of SYNGAP1-related intellectual disability.

At least five SYNGAP1 gene mutations have been identified in people with autism spectrum disorder (ASD), a condition that appears early in childhood development, varies in severity, and is characterized by impaired social skills, communication problems, and repetitive behaviors. These mutations result in a SynGAP protein with impaired function or prevent the production of the protein. Changes in synaptic adaptation in individuals with these mutations may underlie the behavioral abnormalities characteristic of ASD. It is not known why some people with SYNGAP1 gene mutations develop ASD while others have the additional features of SYNCAP1-related intellectual disability (described above).