SYNGAP1

SYNGAP1 encodes SynGAP, a brain-specific Ras/Rap GTPase-activating protein that is one of the most abundant proteins in the postsynaptic density (PSD) of excitatory synapses. SynGAP functions as a dual-specificity GAP for both Ras and Rap small GTPases. By accelerating GTP hydrolysis, SynGAP inactivates these signaling molecules, thereby serving as a negative regulator of Ras-ERK/MAPK and Rap signaling pathways at synapses. This regulation controls AMPA receptor trafficking to the postsynaptic membrane, dendritic spine maturation, and long-term synaptic plasticity. SynGAP is regulated by phosphorylation from CaMKII and CDK5, which modulates its GAP activity and synaptic localization. The protein contains PH, C2, and Ras-GAP domains, along with a C-terminal PDZ-binding motif that anchors it to PSD-95 and related scaffolds. De novo heterozygous loss-of-function mutations cause SYNGAP1-related intellectual disability and epilepsy through haploinsufficiency.

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

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