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    SYNGAP1 synaptic Ras GTPase activating protein 1 [ Homo sapiens (human) ]

    Gene ID: 8831, updated on 27-Nov-2024

    Summary

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    Official Symbol
    SYNGAP1provided by HGNC
    Official Full Name
    synaptic Ras GTPase activating protein 1provided by HGNC
    Primary source
    HGNC:HGNC:11497
    See related
    Ensembl:ENSG00000197283 MIM:603384; AllianceGenome:HGNC:11497
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    MRD5; RASA1; RASA5; SYNGAP
    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. [provided by RefSeq, Nov 2016]
    Expression
    Ubiquitous expression in brain (RPKM 17.6), ovary (RPKM 8.3) and 23 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See SYNGAP1 in Genome Data Viewer
    Location:
    6p21.32
    Exon count:
    23
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (33418167..33453689)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (33239529..33275052)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (33387842..33421466)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene PHD finger protein 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:33393157-33393699 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:33396849-33397470 Neighboring gene cutA divalent cation tolerance homolog Neighboring gene ReSE screen-validated silencer GRCh37_chr6:33405630-33405807 Neighboring gene SYNGAP1 antisense RNA 1 Neighboring gene microRNA 5004 Neighboring gene zinc finger and BTB domain containing 9 Neighboring gene uncharacterized LOC107986537 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:33499692-33500296 Neighboring gene RNA, 7SL, cytoplasmic 26, pseudogene

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Novel SYNGAP1 variant in a patient with intellectual disability and distinctive dysmorphisms. Kimura Y, et al. Congenit Anom (Kyoto), 2018 Nov. PMID 29381230
    2. Differential auditory brain response abnormalities in two intellectual disability conditions: SYNGAP1 mutations and Down syndrome. Côté V, et al. Clin Neurophysiol, 2021 Aug. PMID 34130248
    3. SYNGAP1-DEE: A visual sensitive epilepsy. Lo Barco T, et al. Clin Neurophysiol, 2021 Apr. PMID 33639450
    4. Multi-parametric analysis of 57 SYNGAP1 variants reveal impacts on GTPase signaling, localization, and protein stability. Meili F, et al. Am J Hum Genet, 2021 Jan 7. PMID 33308442, Free PMC Article
    5. Distinct patterns of repetition suppression in Fragile X syndrome, down syndrome, tuberous sclerosis complex and mutations in SYNGAP1. Côté V, et al. Brain Res, 2021 Jan 15. PMID 33189692

    See all (81) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Behavioural and neurodevelopmental characteristics of SYNGAP1.
      Title: Behavioural and neurodevelopmental characteristics of SYNGAP1.
    2. SYNGAP1-related developmental and epileptic encephalopathy: Genotypic and phenotypic characteristics and longitudinal insights.
      Title: SYNGAP1-related developmental and epileptic encephalopathy: Genotypic and phenotypic characteristics and longitudinal insights.
    3. Visual social attention in SYNGAP1-related intellectual disability.
      Title: Visual social attention in SYNGAP1-related intellectual disability.
    4. The Behavioral Profile of SYNGAP1-Related Intellectual Disability.
      Title: The Behavioral Profile of SYNGAP1-Related Intellectual Disability.
    5. Severe behavior problems in SYNGAP1-related disorder: A summary of 11 consecutive patients in a tertiary care specialty clinic.
      Title: Severe behavior problems in SYNGAP1-related disorder: A summary of 11 consecutive patients in a tertiary care specialty clinic.
    6. [Correlation of early neurodevelopmental features of children with SYNGAP1 variants and their genotypes].
      Title: [Correlation of early neurodevelopmental features of children with SYNGAP1 variants and their genotypes].
    7. Discovery of a non-canonical function of SYNGAP1 at early stages of human cortical neurogenesis.
      Title: Discovery of a non-canonical function of SYNGAP1 at early stages of human cortical neurogenesis.
    8. Non-synaptic function of the autism spectrum disorder-associated gene SYNGAP1 in cortical neurogenesis.
      Title: Non-synaptic function of the autism spectrum disorder-associated gene SYNGAP1 in cortical neurogenesis.
    9. Upregulation of SYNGAP1 expression in mice and human neurons by redirecting alternative splicing.
      Title: Upregulation of SYNGAP1 expression in mice and human neurons by redirecting alternative splicing.
    10. The SYNGAP1 3'UTR Variant in ALS Patients Causes Aberrant SYNGAP1 Splicing and Dendritic Spine Loss by Recruiting HNRNPK.
      Title: The SYNGAP1 3'UTR Variant in ALS Patients Causes Aberrant SYNGAP1 Splicing and Dendritic Spine Loss by Recruiting HNRNPK.
    Submit: New GeneRIF Correction See all GeneRIFs (38)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Intellectual disability, autosomal dominant 5
    MedGen: C2675473 OMIM: 612621 GeneReviews: SYNGAP1-Related Intellectual Disability
    		not available

    Copy number response

    Description
    Copy number response
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated 2021-11-09)

    ClinGen Genome Curation PagePubMed
    Triplosensitivity

    No evidence available (Last evaluated 2021-11-09)

    ClinGen Genome Curation Page

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • KIAA1938, DKFZp761G1421

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables GTPase activator activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables SH3 domain binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in Ras protein signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in axonogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in dendrite development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in maintenance of postsynaptic specialization structure IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of Ras protein signal transduction ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative regulation of axonogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of neuron apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in neuron apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in pattern specification process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in receptor clustering IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of MAPK cascade IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of long-term neuronal synaptic plasticity IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of synapse structure or activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of synaptic plasticity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in visual learning IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in dendritic shaft IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in glutamatergic synapse IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in postsynaptic density IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    ras/Rap GTPase-activating protein SynGAP
    Names
    Ras GTPase-activating protein SynGAP
    Ras/Rap GTPase-activating protein 1
    neuronal RasGAP
    synaptic Ras GTPase activating protein 1 homolog
    synaptic Ras GTPase activating protein, 135kDa

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_016137.2 RefSeqGene

      Range
      4996..38620
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_1193

    mRNA and Protein(s)

    1. NM_001130066.2 → NP_001123538.1  ras/Rap GTPase-activating protein SynGAP isoform 2

      Status: REVIEWED

      Source sequence(s)
      AK094225, AK124666, AK307888, AL662799, AL713634, DA057307
      Consensus CDS
      CCDS93894.1
      UniProtKB/TrEMBL
      A0A2R8Y6T2, B7ZCA0
      Related
      ENSP00000416519.4, ENST00000449372.7
      Conserved Domains (5) summary
      cd05136
      Location:415 → 722
      RasGAP_DAB2IP; The DAB2IP family of Ras GTPase-activating proteins includes DAB2IP, nGAP, and Syn GAP. Disabled 2 interactive protein, (DAB2IP; also known as ASK-interacting protein 1 (AIP1)), is a member of the GTPase-activating proteins, down-regulates Ras-mediated...
      pfam09744
      Location:1154 → 1266
      Jnk-SapK_ap_N; JNK_SAPK-associated protein-1
      pfam12004
      Location:719 → 1282
      DUF3498; Domain of unknown function (DUF3498)
      cd04013
      Location:252 → 414
      C2_SynGAP_like; C2 domain present in Ras GTPase activating protein (GAP) family
      cl00273
      Location:136 → 249
      PH-like; Pleckstrin homology-like domain

    2. NM_006772.3 → NP_006763.2  ras/Rap GTPase-activating protein SynGAP isoform 1

      See identical proteins and their annotated locations for NP_006763.2

      Status: REVIEWED

      Source sequence(s)
      AK094225, AK124666, AK307888, AL662799, AL713634, BX282051, DA057307
      Consensus CDS
      CCDS34434.2
      UniProtKB/Swiss-Prot
      A2AB17, A2BEL6, A2BEL7, A8MQC4, Q8TCS2, Q96PV0, Q9UGE2
      UniProtKB/TrEMBL
      A0A1U9X8L0, A0A2R8Y6T2
      Related
      ENSP00000496007.1, ENST00000646630.1
      Conserved Domains (4) summary
      cd04013
      Location:252 → 414
      C2_SynGAP_like; C2 domain present in Ras GTPase activating protein (GAP) family
      cd05136
      Location:405 → 728
      RasGAP_DAB2IP; Ras-GTPase Activating Domain of DAB2IP and similar proteins
      cd13375
      Location:122 → 313
      PH_SynGAP; Synaptic Ras-GTPase activating protein Pleckstrin homology (PH) domain
      pfam12004
      Location:718 → 1310
      DUF3498; Domain of unknown function (DUF3498)

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      33418167..33453689
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047419455.1 → XP_047275411.1  ras/Rap GTPase-activating protein SynGAP isoform X5

    2. XM_047419464.1 → XP_047275420.1  ras/Rap GTPase-activating protein SynGAP isoform X9

    3. XM_047419463.1 → XP_047275419.1  ras/Rap GTPase-activating protein SynGAP isoform X9

      Related
      ENSP00000403636.3, ENST00000418600.7

    4. XM_047419450.1 → XP_047275406.1  ras/Rap GTPase-activating protein SynGAP isoform X13

    5. XM_047419451.1 → XP_047275407.1  ras/Rap GTPase-activating protein SynGAP isoform X1

    6. XM_047419457.1 → XP_047275413.1  ras/Rap GTPase-activating protein SynGAP isoform X6

    7. XM_047419452.1 → XP_047275408.1  ras/Rap GTPase-activating protein SynGAP isoform X2

    8. XM_047419453.1 → XP_047275409.1  ras/Rap GTPase-activating protein SynGAP isoform X3

    9. XM_047419454.1 → XP_047275410.1  ras/Rap GTPase-activating protein SynGAP isoform X4

    10. XM_047419465.1 → XP_047275421.1  ras/Rap GTPase-activating protein SynGAP isoform X14

      UniProtKB/TrEMBL
      B7ZCA0

    11. XM_047419461.1 → XP_047275417.1  ras/Rap GTPase-activating protein SynGAP isoform X9

    12. XM_047419458.1 → XP_047275414.1  ras/Rap GTPase-activating protein SynGAP isoform X7

      Related
      ENSP00000486431.1, ENST00000628646.2

    13. XM_047419460.1 → XP_047275416.1  ras/Rap GTPase-activating protein SynGAP isoform X8

    14. XM_047419467.1 → XP_047275423.1  ras/Rap GTPase-activating protein SynGAP isoform X12

    15. XM_047419456.1 → XP_047275412.1  ras/Rap GTPase-activating protein SynGAP isoform X5

    16. XM_047419462.1 → XP_047275418.1  ras/Rap GTPase-activating protein SynGAP isoform X10

      Related
      ENSP00000412475.2, ENST00000428982.4

    17. XM_047419466.1 → XP_047275422.1  ras/Rap GTPase-activating protein SynGAP isoform X11

    RNA

    1. XR_007059351.1 RNA Sequence

    Reference GRCh38.p14 ALT_REF_LOCI_7

    Genomic

    1. NT_167249.2 Reference GRCh38.p14 ALT_REF_LOCI_7

      Range
      4868790..4902412
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      33239529..33275052
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054356657.1 → XP_054212632.1  ras/Rap GTPase-activating protein SynGAP isoform X5

    2. XM_054356665.1 → XP_054212640.1  ras/Rap GTPase-activating protein SynGAP isoform X9

    3. XM_054356664.1 → XP_054212639.1  ras/Rap GTPase-activating protein SynGAP isoform X9

    4. XM_054356653.1 → XP_054212628.1  ras/Rap GTPase-activating protein SynGAP isoform X1

    5. XM_054356659.1 → XP_054212634.1  ras/Rap GTPase-activating protein SynGAP isoform X6

    6. XM_054356654.1 → XP_054212629.1  ras/Rap GTPase-activating protein SynGAP isoform X2

    7. XM_054356655.1 → XP_054212630.1  ras/Rap GTPase-activating protein SynGAP isoform X3

    8. XM_054356656.1 → XP_054212631.1  ras/Rap GTPase-activating protein SynGAP isoform X4

    9. XM_054356662.1 → XP_054212637.1  ras/Rap GTPase-activating protein SynGAP isoform X9

    10. XM_054356660.1 → XP_054212635.1  ras/Rap GTPase-activating protein SynGAP isoform X7

    11. XM_054356661.1 → XP_054212636.1  ras/Rap GTPase-activating protein SynGAP isoform X8

    12. XM_054356667.1 → XP_054212642.1  ras/Rap GTPase-activating protein SynGAP isoform X12

    13. XM_054356658.1 → XP_054212633.1  ras/Rap GTPase-activating protein SynGAP isoform X5

    14. XM_054356663.1 → XP_054212638.1  ras/Rap GTPase-activating protein SynGAP isoform X10

    15. XM_054356666.1 → XP_054212641.1  ras/Rap GTPase-activating protein SynGAP isoform X11

    RNA

    1. XR_008487455.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q96PV0.4 GenPept UniProtKB/Swiss-Prot:Q96PV0

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