protein
Ras/Rap GTPase-activating protein SynGAP
Gene
SYNGAP1
Organism
Homo sapiens(9606)
Length
1343 aa
Mass
148,284 Da
SynGAP (SYNGAP1) is a Ras/Rap GTPase-activating protein and major constituent of the postsynaptic density in excitatory synapses (UniProt: Q96PV0). It functions as an inhibitory regulator of the Ras-cAMP pathway and exhibits dual GTPase-activating specificity for Ras and Rap, playing a key role in NMDAR-dependent synaptic plasticity, AMPAR trafficking, and the regulation of excitatory postsynaptic currents.
SynGAP is a critical member of the NMDAR signaling complex at excitatory synapses and is implicated in brain injury-related learning and memory deficits. Loss-of-function mutations in SYNGAP1 cause autosomal dominant intellectual developmental disorder-5 (MRD5), characterized by global developmental delay, hypotonia, moderate-to-severe intellectual disability, and severe language impairment.
SYNGAP1 is classified as a high-confidence autism-risk gene (SFARI Cat 1) with a syndromic presentation. Epilepsy and autism spectrum disorder are documented clinical features in some MRD5 patients, reflecting the protein's essential role in glutamatergic synaptic signaling and neurodevelopmental processes.
Generated from the curated entity record below. May contain errors — verify against source links.
Genetic Evidence · ASD
High confidence — strong genetic evidence from multiple studies
Source: SFARI Gene database · gene.sfari.org
Related Publications
Browse all →Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
Ruzzo Elizabeth K et al.Cell2019PMID 31398340Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
Guo Hui et al.Molecular autism2018PMID 30564305Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
C Yuen Ryan K et al.Nature neuroscience2017PMID 28263302Identification of common genetic risk variants for autism spectrum disorder.
Grove Jakob et al.Nature genetics2019PMID 30804558Synaptic, transcriptional and chromatin genes disrupted in autism.
De Rubeis Silvia et al.Nature2014PMID 25363760
Function
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)
Disease associations
Intellectual developmental disorder, autosomal dominant 5MRD5
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.
Sources
Last updated 5/6/2026, 5:25:14 AM