SYNGAP1

This gene encodes a Ras GTPase activating protein that is a member of the N-methyl-D-aspartate receptor complex. The N-terminal domain of the protein contains a Ras-GAP domain, a pleckstrin homology domain, and a C2 domain that may be involved in binding of calcium and phospholipids. The C-terminal domain consists of a ten histidine repeat region, serine and tyrosine phosphorylation sites, and a T/SXV motif required for postsynaptic scaffold protein interaction. The encoded protein negatively regulates Ras, Rap and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor trafficking to the postsynaptic membrane to regulate synaptic plasticity and neuronal homeostasis. Allelic variants of this gene are associated with intellectual disability and autism spectrum disorder. Alternative splicing results in multiple transcript variants.

synaptic Ras GTPase activating protein 1

Major constituent of the PSD essential for postsynaptic signaling. Inhibitory regulator of the Ras-cAMP pathway. Member of the NMDAR signaling complex in excitatory synapses, it may play a role in NMDAR-dependent control of AMPAR potentiation, AMPAR membrane trafficking and synaptic plasticity. Regulates AMPAR-mediated miniature excitatory postsynaptic currents. Exhibits dual GTPase-activating specificity for Ras and Rap. May be involved in certain forms of brain injury, leading to long-term learning and memory deficits (By similarity).

Biological Process axonogenesisIEA:Ensembl
Biological Process dendrite developmentIEA:Ensembl
Biological Process maintenance of postsynaptic specialization structureIEA:Ensembl
Biological Process negative regulation of axonogenesisIEA:Ensembl
Biological Process negative regulation of neuron apoptotic processIEA:Ensembl
Biological Process negative regulation of Ras protein signal transductionISS:UniProtKB
Biological Process neuron apoptotic processIEA:Ensembl
Biological Process pattern specification processIEA:Ensembl
Biological Process Ras protein signal transductionIEA:Ensembl
Biological Process receptor clusteringIEA:Ensembl
Biological Process regulation of GTPase activityIEA:InterPro
Biological Process regulation of long-term neuronal synaptic plasticityIEA:Ensembl
Biological Process regulation of MAPK cascadeIEA:Ensembl
Biological Process regulation of synapse structure or activityIEA:Ensembl
Biological Process regulation of synaptic plasticityISS:UniProtKB
Biological Process visual learningIEA:Ensembl

cytosol
dendritic shaft
glutamatergic synapse
plasma membrane
postsynaptic density

Intellectual developmental disorder, autosomal dominant 5 (MRD5):
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD5 patients show global developmental delay with delayed motor development, hypotonia, moderate-to-severe intellectual disability, and severe language impairment. Epilepsy and autism can be present in some patients.

Phosphorylated by CaM-kinase II. Dephosphorylated upon NMDA receptor activation or SYNGAP1/MPDZ complex disruption. Phosphorylation by PLK2 promotes its activity (By similarity).