SYNGAP1
Synaptic Ras GTPase Activating Protein 1
Gene Information Card
| Symbol | SYNGAP1 |
|---|---|
| Full Name | Synaptic Ras GTPase Activating Protein 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 6p21.32 |
| NCBI Gene ID | 8831 ncbi.nlm.nih.gov/gene/8831 |
| Ensembl ID | ENSG00000100162 |
| UniProt ID | Q96PV0 |
| OMIM ID | 603384 |
| HGNC ID | 11497 |
| Aliases | SYNGAP, MRD5, RASA1, RASA5 |
Description
The SYNGAP1 gene encodes a Ras GTPase-activating protein that is critical for synaptic plasticity and cognitive function. It is predominantly expressed in the brain and regulates the Ras-MAPK signaling pathway at excitatory synapses. Loss-of-function mutations in SYNGAP1 cause a neurodevelopmental disorder characterized by intellectual disability, epilepsy, autism spectrum disorder, and language impairment.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| SYNGAP1-related intellectual disability (MRD5) | Loss-of-function mutations impair synaptic Ras signaling, leading to altered dendritic spine morphology and synaptic plasticity | ClinVar, OMIM |
| Epilepsy, early-onset (often with myoclonic seizures) | Haploinsufficiency disrupts excitatory/inhibitory balance in cortical circuits | ClinVar, PubMed |
| Autism spectrum disorder | SYNGAP1 mutations affect synaptic maturation and neuronal connectivity | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | High |
| Brain (hippocampus) | 11.8 | High |
| Brain (cerebellum) | 8.2 | Medium |
| Testis | 2.1 | Low |
| Other tissues | <1.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.3 | High expression |
| U-87 MG (glioblastoma) | 9.7 | Medium expression |
| HEK293 (embryonic kidney) | 0.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1684C>T (p.Arg562*) | Nonsense | ~5% of cases | Loss of function; premature truncation |
| c.2663delC (p.Pro888Leufs*2) | Frameshift | ~3% of cases | Loss of function; protein truncation |
| c.3583G>A (p.Gly1195Arg) | Missense | Rare | Likely loss of function; impaired GAP activity |
Mutation functional classification
Loss of Function (LOF)
Most SYNGAP1 mutations are loss-of-function (nonsense, frameshift, splice-site, or missense with reduced GAP activity), leading to haploinsufficiency.
Gain of Function (GOF)
No gain-of-function mutations have been reported for SYNGAP1.
Dominant Negative (DN)
Dominant-negative effects are not well established; most pathogenic variants act via haploinsufficiency.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activator activity | • Ras GTPase binding |
| • synaptic signaling | • dendritic spine morphogenesis |
| • regulation of long-term synaptic potentiation |
Pathways
• Ras-MAPK signaling pathway
• Synaptic plasticity pathway
• Glutamatergic synapse signaling
Protein Summary
SYNGAP1 is a 1,343-amino-acid protein that contains a Ras-GAP domain, a PH domain, and a C2 domain. It localizes to the postsynaptic density of excitatory synapses, where it inactivates Ras by stimulating GTP hydrolysis. This regulation is essential for proper synaptic development, plasticity, and cognitive function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SYNGAP1 Knockout HEK293 Cell Line | EDJ-KQ677 | Human | 8831 | Details Get a Quote |
| SYNGAP1 Knockout A-549 Cell Line | EDJ-KQ20570 | Human | 8831 | Details Get a Quote |
| SYNGAP1 Knockout HCT 116 Cell Line | EDJ-KQ20572 | Human | 8831 | Details Get a Quote |
| SYNGAP1 Knockout HeLa Cell Line | EDJ-KQ20573 | Human | 8831 | Details Get a Quote |
