Gene: SYNGAP1

Alternate names for this Gene: MRD5|RASA1|RASA5|SYNGAP

Gene Summary: 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.

Gene is located in Chromosome: 6

Location in Chromosome : 6p21.32

Description of this Gene: synaptic Ras GTPase activating protein 1

Type of Gene: protein-coding

rs9461856 in SYNGAP1 gene and Child Development Disorders, Pervasive PMID 28540026 2017 Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.

rs1131692154 in SYNGAP1 gene and Dysmorphic features PMID 26079862 2015 De novo, heterozygous, loss-of-function mutations in SYNGAP1 cause a syndromic form of intellectual disability.

PMID 25533962 2015 Large-scale discovery of novel genetic causes of developmental disorders.

PMID 28576131 2017 Analysis of 31-year-old patient with SYNGAP1 gene defect points to importance of variants in broader splice regions and reveals developmental trajectory of SYNGAP1-associated phenotype: case report.

PMID 21376300 2011 Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability.

PMID 27827368 2016 Decrease of SYNGAP1 in GABAergic cells impairs inhibitory synapse connectivity, synaptic inhibition and cognitive function.

PMID 26989088 2016 Genetic and neurodevelopmental spectrum of SYNGAP1-associated intellectual disability and epilepsy.

PMID 23934111 2013 De novo mutations in epileptic encephalopathies.

PMID 24267886 2013 Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism.

PMID 23161826 2013 Mutations in SYNGAP1 cause intellectual disability, autism, and a specific form of epilepsy by inducing haploinsufficiency.

PMID 23033978 2012 Diagnostic exome sequencing in persons with severe intellectual disability.

PMID 22604720 2012 Evolution and functional impact of rare coding variation from deep sequencing of human exomes.

PMID 23708187 2013 Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.

PMID 23020937 2012 Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study.

PMID 20531469 2010 Functional impact of global rare copy number variation in autism spectrum disorders.

PMID 23141534 2012 Pathogenic SYNGAP1 mutations impair cognitive development by disrupting maturation of dendritic spine synapses.

PMID 15312654 2004 SynGAP-MUPP1-CaMKII synaptic complexes regulate p38 MAP kinase activity and NMDA receptor-dependent synaptic AMPA receptor potentiation.

PMID 19196676 2009 Mutations in SYNGAP1 in autosomal nonsyndromic mental retardation.

PMID 21237447 2011 De novo SYNGAP1 mutations in nonsyndromic intellectual disability and autism.

rs1131691979 in SYNGAP1 gene and Mental Retardation, Autosomal Dominant 5 PMID 25418537 2014 Recurrent de novo mutations implicate novel genes underlying simplex autism risk.

PMID 21237447 2011 De novo SYNGAP1 mutations in nonsyndromic intellectual disability and autism.

PMID 26989088 2016 Genetic and neurodevelopmental spectrum of SYNGAP1-associated intellectual disability and epilepsy.

PMID 23161826 2013 Mutations in SYNGAP1 cause intellectual disability, autism, and a specific form of epilepsy by inducing haploinsufficiency.

PMID 21076407 2010 A de novo paradigm for mental retardation.

PMID 19196676 2009 Mutations in SYNGAP1 in autosomal nonsyndromic mental retardation.

PMID 23708187 2013 Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.

PMID 28554332 2017 Genomic diagnosis for children with intellectual disability and/or developmental delay.

PMID 25167861 2014 Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.

PMID 26795593 2016 Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy.

PMID 25356970 2015 Enhanced utility of family-centered diagnostic exome sequencing with inheritance model-based analysis: results from 500 unselected families with undiagnosed genetic conditions.

rs1554122252 in SYNGAP1 gene and Movement Disorders PMID 23020937 2012 Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study.

PMID 21376300 2011 Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability.

PMID 19196676 2009 Mutations in SYNGAP1 in autosomal nonsyndromic mental retardation.

PMID 27827368 2016 Decrease of SYNGAP1 in GABAergic cells impairs inhibitory synapse connectivity, synaptic inhibition and cognitive function.

PMID 20531469 2010 Functional impact of global rare copy number variation in autism spectrum disorders.

PMID 23141534 2012 Pathogenic SYNGAP1 mutations impair cognitive development by disrupting maturation of dendritic spine synapses.

PMID 21237447 2011 De novo SYNGAP1 mutations in nonsyndromic intellectual disability and autism.

PMID 23934111 2013 De novo mutations in epileptic encephalopathies.

PMID 24267886 2013 Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism.

PMID 26079862 2015 De novo, heterozygous, loss-of-function mutations in SYNGAP1 cause a syndromic form of intellectual disability.

PMID 23161826 2013 Mutations in SYNGAP1 cause intellectual disability, autism, and a specific form of epilepsy by inducing haploinsufficiency.

PMID 15312654 2004 SynGAP-MUPP1-CaMKII synaptic complexes regulate p38 MAP kinase activity and NMDA receptor-dependent synaptic AMPA receptor potentiation.

PMID 23033978 2012 Diagnostic exome sequencing in persons with severe intellectual disability.

PMID 23708187 2013 Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.

PMID 25533962 2015 Large-scale discovery of novel genetic causes of developmental disorders.

PMID 28576131 2017 Analysis of 31-year-old patient with SYNGAP1 gene defect points to importance of variants in broader splice regions and reveals developmental trajectory of SYNGAP1-associated phenotype: case report.

PMID 26989088 2016 Genetic and neurodevelopmental spectrum of SYNGAP1-associated intellectual disability and epilepsy.

PMID 22604720 2012 Evolution and functional impact of rare coding variation from deep sequencing of human exomes.

rs1131692154 in SYNGAP1 gene and Muscle hypotonia PMID 15312654 2004 SynGAP-MUPP1-CaMKII synaptic complexes regulate p38 MAP kinase activity and NMDA receptor-dependent synaptic AMPA receptor potentiation.

PMID 28576131 2017 Analysis of 31-year-old patient with SYNGAP1 gene defect points to importance of variants in broader splice regions and reveals developmental trajectory of SYNGAP1-associated phenotype: case report.

PMID 26989088 2016 Genetic and neurodevelopmental spectrum of SYNGAP1-associated intellectual disability and epilepsy.

PMID 25533962 2015 Large-scale discovery of novel genetic causes of developmental disorders.

PMID 24267886 2013 Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism.

PMID 23020937 2012 Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study.

PMID 27827368 2016 Decrease of SYNGAP1 in GABAergic cells impairs inhibitory synapse connectivity, synaptic inhibition and cognitive function.

PMID 19196676 2009 Mutations in SYNGAP1 in autosomal nonsyndromic mental retardation.

PMID 23141534 2012 Pathogenic SYNGAP1 mutations impair cognitive development by disrupting maturation of dendritic spine synapses.

PMID 20531469 2010 Functional impact of global rare copy number variation in autism spectrum disorders.

PMID 23934111 2013 De novo mutations in epileptic encephalopathies.

PMID 21376300 2011 Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability.

PMID 22604720 2012 Evolution and functional impact of rare coding variation from deep sequencing of human exomes.

PMID 23033978 2012 Diagnostic exome sequencing in persons with severe intellectual disability.

PMID 21237447 2011 De novo SYNGAP1 mutations in nonsyndromic intellectual disability and autism.

PMID 26079862 2015 De novo, heterozygous, loss-of-function mutations in SYNGAP1 cause a syndromic form of intellectual disability.

PMID 23708187 2013 Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.

PMID 23161826 2013 Mutations in SYNGAP1 cause intellectual disability, autism, and a specific form of epilepsy by inducing haploinsufficiency.

rs211456 in SYNGAP1 gene and Rheumatoid Arthritis PMID 19503088 2009 REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis.

rs9461856 in SYNGAP1 gene and Schizophrenia PMID 30285260 2019 Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect.

PMID 28540026 2017 Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.

PMID 26198764 2015 Genome-wide association study of schizophrenia in Ashkenazi Jews.