3671 lines
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Entry
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- *603384 - SYNAPTIC RAS-GTPase-ACTIVATING PROTEIN 1; SYNGAP1
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*603384</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/603384">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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</nav>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000197283;t=ENST00000646630" class="mim-tip-hint" title="Genome databases for vertebrates and other eukaryotic species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=8831" class="mim-tip-hint" title="Detailed views of the complete genomes of selected organisms from vertebrates to protozoa." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Genome Viewer', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Genome Viewer</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=603384" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000197283;t=ENST00000646630" class="mim-tip-hint" title="Transcript-based views for coding and noncoding DNA." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl (MANE Select)</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001130066,NM_006772,XM_047419450,XM_047419451,XM_047419452,XM_047419453,XM_047419454,XM_047419455,XM_047419456,XM_047419457,XM_047419458,XM_047419460,XM_047419461,XM_047419462,XM_047419463,XM_047419464,XM_047419465,XM_047419466,XM_047419467,XR_007059351" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_006772" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq (MANE)', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq (MANE Select)</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=603384" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=16018&isoform_id=16018_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
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<div><a href="https://www.proteinatlas.org/search/SYNGAP1" class="mim-tip-hint" title="The Human Protein Atlas contains information for a large majority of all human protein-coding genes regarding the expression and localization of the corresponding proteins based on both RNA and protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HumanProteinAtlas', 'domain': 'proteinatlas.org'})">Human Protein Atlas</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/protein/3169121,19584303,119624140,119624141,119624142,119624143,150421676,194248068,194248070,1159611419,1159611421,1159611423,1159611425,1159611427,2217363415,2217363417,2217363419,2217363421,2217363423,2217363425,2217363427,2217363429,2217363431,2217363434,2217363436,2217363438,2217363440,2217363442,2217363444,2217363446,2217363448,2462611058,2462611060,2462611062,2462611064,2462611066,2462611068,2462611070,2462611072,2462611075,2462611077,2462611079,2462611081,2462611083,2462611085,2462611087,2468022615,2468022617,2468022619,2468022621,2476336104,2476336107" class="mim-tip-hint" title="NCBI protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Protein', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Protein</a></div>
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<div><a href="https://www.uniprot.org/uniprotkb/Q96PV0" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="http://biogps.org/#goto=genereport&id=8831" class="mim-tip-hint" title="The Gene Portal Hub; customizable portal of gene and protein function information." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'BioGPS', 'domain': 'biogps.org'})">BioGPS</a></div>
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<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000197283;t=ENST00000646630" class="mim-tip-hint" title="Orthologs, paralogs, regulatory regions, and splice variants." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=SYNGAP1" class="mim-tip-hint" title="The Human Genome Compendium; web-based cards integrating automatically mined information on human genes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneCards', 'domain': 'genecards.org'})">GeneCards</a></div>
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<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=SYNGAP1" class="mim-tip-hint" title="Terms, defined using controlled vocabulary, representing gene product properties (biologic process, cellular component, molecular function) across species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneOntology', 'domain': 'amigo.geneontology.org'})">Gene Ontology</a></div>
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<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+8831" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<dd><a href="http://v1.marrvel.org/search/gene/SYNGAP1" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></dd>
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<dd><a href="https://monarchinitiative.org/NCBIGene:8831" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/8831" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr6&hgg_gene=ENST00000646630.1&hgg_start=33418167&hgg_end=33453689&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:11497" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:11497" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/syngap1" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=603384[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=603384[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/SYNGAP1/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000197283" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=SYNGAP1" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=SYNGAP1" class="mim-tip-hint" title="GWAS Central; summary level genotype-to-phenotype information from genetic association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Central', 'domain': 'gwascentral.org'})">GWAS Central </a></div>
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<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=SYNGAP1" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=SYNGAP1&upstreamSize=0&downstreamSize=0&x=0&y=0" class="mim-tip-hint" title="National Heart, Lung, and Blood Institute Exome Variant Server." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NHLBI EVS', 'domain': 'evs.gs.washington.edu'})">NHLBI EVS</a></div>
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<div><a href="https://www.pharmgkb.org/gene/PA36279" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/gene/HGNC:11497" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0261570.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:3039785" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
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<div><a href="http://v1.marrvel.org/search/gene/SYNGAP1#HomologGenesPanel" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></div>
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<div><a href="http://www.informatics.jax.org/marker/MGI:3039785" class="mim-tip-hint" title="Mouse Genome Informatics; international database resource for the laboratory mouse, including integrated genetic, genomic, and biological data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Gene', 'domain': 'informatics.jax.org'})">MGI Mouse Gene</a></div>
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<div><a href="https://www.mmrrc.org/catalog/StrainCatalogSearchForm.php?search_query=" class="mim-tip-hint" title="Mutant Mouse Resource & Research Centers." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MMRRC', 'domain': 'mmrrc.org'})">MMRRC</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/8831/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=8831" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00001516;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-060503-370" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://catalog.coriell.org/Search?q=OmimNum:603384" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:8831" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=SYNGAP1&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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603384
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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SYNAPTIC RAS-GTPase-ACTIVATING PROTEIN 1; SYNGAP1
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</span>
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</h3>
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</div>
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<div>
|
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
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GTPase-ACTIVATING PROTEIN, RAS, SYNAPTIC, 135-KD, RAT, HOMOLOG OF<br />
|
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RAS-GTPase-ACTIVATING PROTEIN, SYNAPTIC, 135-KD, RAT, HOMOLOG OF<br />
|
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SYNAPTIC RAS-GTPase-ACTIVATING PROTEIN, 135-KD, RAT, HOMOLOG OF<br />
|
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SYNGAP, p135, RAT, HOMOLOG OF; SYNGAP
|
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</span>
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</h4>
|
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
|
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=SYNGAP1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">SYNGAP1</a></em></strong>
|
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</span>
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</p>
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/6/401?start=-3&limit=10&highlight=401">6p21.32</a>
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr6:33418167-33453689&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">6:33,418,167-33,453,689</a> </span>
|
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</em>
|
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
|
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</p>
|
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</div>
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<div>
|
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<br />
|
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</div>
|
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<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
|
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<tr class="active">
|
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<th>
|
|
Location
|
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</th>
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<th>
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|
Phenotype
|
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</th>
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<th>
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|
Phenotype <br /> MIM number
|
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</th>
|
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<th>
|
|
Inheritance
|
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</th>
|
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<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
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</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/6/401?start=-3&limit=10&highlight=401">
|
|
6p21.32
|
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</a>
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<p>The SYNGAP1 gene encodes a brain-specific synaptic Ras GTP-ase activating protein that is largely localized to dendritic spines in neocortical pyramidal neurons, where it suppresses signaling pathways linked to NMDA receptor (NMDAR)-mediated synaptic plasticity and AMPA receptor (AMPAR) membrane insertion (summary by <a href="#4" class="mim-tip-reference" title="Clement, J. P., Aceti, M., Creson, T. K., Ozkan, E. D., Shi, Y., Reish, N. J., Almonte, A. G., Miller, B. H., Wiltgen, B. J., Miller, C. A., Xu, X., Rumbaugh, G. <strong>Pathogenic SYNGAP1 mutations impair cognitive development by disrupting maturation of dendritic spine synapses.</strong> Cell 151: 709-723, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23141534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23141534</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23141534[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.cell.2012.08.045" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23141534">Clement et al., 2012</a> and <a href="#1" class="mim-tip-reference" title="Berryer, M. H., Hamdan, F. F., Klitten, L. L., Moller, R. S., Carmant, L., Schwartzentruber, J., Patry, L., Dobrzeniecka, S., Rochefort, D., Neugnot-Cerioli, M., Lacaille, J.-C., Niu, Z., and 15 others. <strong>Mutations in SYNGAP1 cause intellectual disability, autism, and a specific form of epilepsy by inducing haploinsufficiency.</strong> Hum. Mutat. 34: 385-394, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23161826/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23161826</a>] [<a href="https://doi.org/10.1002/humu.22248" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23161826">Berryer et al., 2013</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=23141534+23161826" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Calmodulin-dependent protein kinase II (CaMKII; e.g., <a href="/entry/114078">114078</a>) is activated in hippocampal neurons by the rise in intracellular calcium that follows stimulation of NMDA receptors (e.g., <a href="/entry/138249">138249</a>). CaMKII is concentrated in the postsynaptic density (PSD), a complex of proteins that colocalize with NMDA receptors at synapses. To determine the targets of CaMKII at the postsynaptic site, <a href="#3" class="mim-tip-reference" title="Chen, H.-J., Rojas-Soto, M., Oguni, A., Kennedy, M. B. <strong>A synaptic Ras-GTPase activating protein (p135 SynGAP) inhibited by CaM kinase II.</strong> Neuron 20: 895-904, 1998. Note: Erratum: Neuron 33: 151 only, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9620694/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9620694</a>] [<a href="https://doi.org/10.1016/s0896-6273(00)80471-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9620694">Chen et al. (1998)</a> sequenced tryptic peptides from rat forebrain PSDs, performed RT-PCR using degenerate primers based on the peptide sequences, and screened a rat brain cDNA library with the PCR products. They isolated cDNAs encoding a novel synaptic Ras-GTPase-activating protein, p135-Syngap, which is a major component of the PSD. The deduced p135-Syngap protein contains a putative pleckstrin homology domain in the N-terminal segment; a region showing partial identity to the C2 domain of p120-RASGAP; a RasGAP motif; a proline-rich, putative SH3 domain-binding site; 29 consensus sites for phosphorylation by CaMKII; and a C-terminal consensus sequence that can bind to the scaffold protein PSD95 (<a href="/entry/602887">602887</a>). The authors found that p135-Syngap is most highly expressed in the brain, localizes to glutamatergic synapses, and forms a complex with PSD95. <a href="#3" class="mim-tip-reference" title="Chen, H.-J., Rojas-Soto, M., Oguni, A., Kennedy, M. B. <strong>A synaptic Ras-GTPase activating protein (p135 SynGAP) inhibited by CaM kinase II.</strong> Neuron 20: 895-904, 1998. Note: Erratum: Neuron 33: 151 only, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9620694/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9620694</a>] [<a href="https://doi.org/10.1016/s0896-6273(00)80471-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9620694">Chen et al. (1998)</a> also isolated cDNAs representing alternatively spliced p135-Syngap transcripts, 1 of which encodes a variant p135-Syngap protein lacking the C-terminal consensus site. <a href="#8" class="mim-tip-reference" title="Oh, J. S., Chen, H.-J., Rojas-Soto, M., Oguni, A., Kennedy, M. B. <strong>Erratum.</strong> Neuron 33: 151 only, 2002."None>Oh et al. (2002)</a> corrected the observation of <a href="#3" class="mim-tip-reference" title="Chen, H.-J., Rojas-Soto, M., Oguni, A., Kennedy, M. B. <strong>A synaptic Ras-GTPase activating protein (p135 SynGAP) inhibited by CaM kinase II.</strong> Neuron 20: 895-904, 1998. Note: Erratum: Neuron 33: 151 only, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9620694/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9620694</a>] [<a href="https://doi.org/10.1016/s0896-6273(00)80471-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9620694">Chen et al. (1998)</a> regarding the activity of p135-SYNGAP and stated that the Ras-GTPase-activating protein is phosphorylated, rather than inhibited, by CaMKII. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9620694" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The sequence of a human cosmid clone from chromosome 6 that contains the first 2 exons of a human homolog of rat p135-Syngap, named SYNGAP1, has been deposited in GenBank (<a href="https://www.ncbi.nlm.nih.gov/search/all/?term=AL021366" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">AL021366</a>).</p><p>SYNGAP1 is expressed throughout the forebrain, with particularly high levels in the hippocampus. In mice, <a href="#4" class="mim-tip-reference" title="Clement, J. P., Aceti, M., Creson, T. K., Ozkan, E. D., Shi, Y., Reish, N. J., Almonte, A. G., Miller, B. H., Wiltgen, B. J., Miller, C. A., Xu, X., Rumbaugh, G. <strong>Pathogenic SYNGAP1 mutations impair cognitive development by disrupting maturation of dendritic spine synapses.</strong> Cell 151: 709-723, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23141534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23141534</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23141534[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.cell.2012.08.045" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23141534">Clement et al. (2012)</a> found peak expression of the Syngap1 gene in the hippocampus around postnatal day 14. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23141534" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#10" class="mim-tip-reference" title="Tomoda, T., Kim, J. H., Zhan, C., Hatten, M. E. <strong>Role of Unc51.1 and its binding partners in CNS axon outgrowth.</strong> Genes Dev. 18: 541-558, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15014045/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15014045</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15014045[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1101/gad.1151204" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15014045">Tomoda et al. (2004)</a> found that SynGAP, a negative regulator of Ras (<a href="/entry/190020">190020</a>), was expressed within axons and growth cones of developing mouse granule cells. Overexpression of SynGAP blocked neurite outgrowth by a mechanism that involved a Ras-like GTPase cascade. Using a yeast 2-hybrid assay, <a href="#10" class="mim-tip-reference" title="Tomoda, T., Kim, J. H., Zhan, C., Hatten, M. E. <strong>Role of Unc51.1 and its binding partners in CNS axon outgrowth.</strong> Genes Dev. 18: 541-558, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15014045/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15014045</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15014045[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1101/gad.1151204" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15014045">Tomoda et al. (2004)</a> determined that the C terminus of mouse Unc51.1 (<a href="/entry/603168">603168</a>) bound the C terminus of SynGAP. Both proteins localized to the membrane fraction of mouse cerebral cortex lysates. Using a reporter assay, <a href="#10" class="mim-tip-reference" title="Tomoda, T., Kim, J. H., Zhan, C., Hatten, M. E. <strong>Role of Unc51.1 and its binding partners in CNS axon outgrowth.</strong> Genes Dev. 18: 541-558, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15014045/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15014045</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15014045[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1101/gad.1151204" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15014045">Tomoda et al. (2004)</a> found that Unc51.1 inhibited SynGAP through its kinase activity. They concluded that Unc51.1 and SynGAP function cooperatively in axon formation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15014045" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Rumbaugh, G., Adams, J. P., Kim, J. H., Huganir, R. L. <strong>SynGAP regulates synaptic strength and mitogen-activated protein kinases in cultured neurons.</strong> Proc. Nat. Acad. Sci. 103: 4344-4351, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16537406/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16537406</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16537406[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0600084103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16537406">Rumbaugh et al. (2006)</a> found that SynGAP1 regulated AMPA receptor (AMPAR; see <a href="/entry/138248">138248</a>) trafficking, excitatory synaptic transmission, and the number of silent synapses (i.e., excitatory synapses that lack functional AMPARs) in rodent hippocampal and cortical cultured neurons. The results suggested that SynGAP1 affects these characteristics by regulating the MAP kinase (see MAPK1; <a href="/entry/176948">176948</a>) signaling pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16537406" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In 3 of 94 patients with nonsyndromic intellectual developmental disorder-5 (MRD5; <a href="/entry/612621">612621</a>), <a href="#7" class="mim-tip-reference" title="Hamdan, F. F., Gauthier, J., Spiegelman, D., Noreau, A., Yang, Y., Pellerin, S., Dobrzeniecka, S., Cote, M., Perreault-Linck, E., Carmant, L., D'Anjou, G., Fombonne, E., and 13 others. <strong>Mutations in SYNGAP1 in autosomal nonsyndromic mental retardation.</strong> New Eng. J. Med. 360: 599-605, 2009. Note: Erratum: New Eng. J. Med. 361: 1814 only, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19196676/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19196676</a>] [<a href="https://doi.org/10.1056/NEJMoa0805392" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19196676">Hamdan et al. (2009)</a> identified 3 different de novo heterozygous truncating mutations in the SYNGAP1 gene (<a href="#0001">603384.0001</a>-<a href="#0003">603384.0003</a>). All patients showed global developmental delay with delayed motor development, hypotonia, moderate to severe mental retardation, and severe language impairment without dysmorphic features. Nonpathologic missense variants in the SYNGAP1 gene were identified in 9 of 142 individuals with autism spectrum disorders and 6 of 143 individuals with schizophrenia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19196676" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 3 of 60 patients with nonsyndromic intellectual disability, including 30 with autism spectrum disorder and 9 with epilepsy, <a href="#6" class="mim-tip-reference" title="Hamdan, F. F., Daoud, H., Piton, A., Gauthier, J., Dobrzeniecka, S., Krebs, M.-O., Joober, R., Lacaille, J.-C., Nadeau, A., Milunsky, J. M., Wang, Z., Carmant, L., Mottron, L., Beauchamp, M. H., Rouleau, G. A., Michaud, J. L. <strong>De novo SYNGAP1 mutations in nonsyndromic intellectual disability and autism.</strong> Biol. Psychiat. 69: 898-901, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21237447/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21237447</a>] [<a href="https://doi.org/10.1016/j.biopsych.2010.11.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21237447">Hamdan et al. (2011)</a> identified de novo heterozygous truncating mutations in the SYNGAP1 gene (see, e.g., <a href="#0005">603384.0005</a> and <a href="#0006">603384.0006</a>). The children also showed behavioral abnormalities and mood problems. Two had well-controlled epilepsy and acquired microcephaly, and 1 had autism, thus expanding the phenotypic spectrum associated with SYNGAP1 mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21237447" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Berryer, M. H., Hamdan, F. F., Klitten, L. L., Moller, R. S., Carmant, L., Schwartzentruber, J., Patry, L., Dobrzeniecka, S., Rochefort, D., Neugnot-Cerioli, M., Lacaille, J.-C., Niu, Z., and 15 others. <strong>Mutations in SYNGAP1 cause intellectual disability, autism, and a specific form of epilepsy by inducing haploinsufficiency.</strong> Hum. Mutat. 34: 385-394, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23161826/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23161826</a>] [<a href="https://doi.org/10.1002/humu.22248" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23161826">Berryer et al. (2013)</a> identified 5 different SYNGAP1 mutations (see, e.g., <a href="#0007">603384.0007</a> and <a href="#0008">603384.0008</a>) in 5 unrelated patients with nonsyndromic intellectual disability. There were 3 truncating mutations and 2 missense mutations. These patients were identified by targeted sequencing of the SYNGAP1 gene in several cohorts including a total of 34 patients with nonsyndromic intellectual disability. Of the 5 with mutations, 4 had early-childhood onset of epilepsy, 3 had autism, and 3 had behavioral abnormalities. There were no notable dysmorphic features or structural brain abnormalities. Four of the mutations occurred de novo; 1 was inherited from a mildly affected parent who was mosaic for the mutation. None of the mutant proteins were detected in neuronal cells transfected with the mutations, suggesting decreased stability, even of the missense mutations. Studies in cortical pyramidal neurons showed that the missense mutations were unable to suppress activity-mediated ERK (<a href="/entry/176872">176872</a>), consistent with a loss of protein function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23161826" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Carvill, G. L., Heavin, S. B., Yendle, S. C., McMahon, J. M., O'Roak, B. J., Cook, J., Khan, A., Dorschner, M. O., Weaver, M., Calvert, S., Malone, S., Wallace, G., and 22 others. <strong>Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.</strong> Nature Genet. 45: 825-830, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23708187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23708187</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23708187[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2646" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23708187">Carvill et al. (2013)</a> reported 5 unrelated patients with mental retardation and epileptic encephalopathy associated with heterozygous truncating mutations in the SYNGAP1 gene (see, e.g., <a href="#0009">603384.0009</a>-<a href="#0010">603384.0010</a>). All had delayed development and onset of various seizure types between 6 months and 3 years that were associated with multiple EEG abnormalities and cognitive regression. Four patients had autistic spectrum disorder. In 2 patients, the mutations occurred de novo; in the other 3 patients, DNA from one or both parents was not available for study. <a href="#2" class="mim-tip-reference" title="Carvill, G. L., Heavin, S. B., Yendle, S. C., McMahon, J. M., O'Roak, B. J., Cook, J., Khan, A., Dorschner, M. O., Weaver, M., Calvert, S., Malone, S., Wallace, G., and 22 others. <strong>Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.</strong> Nature Genet. 45: 825-830, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23708187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23708187</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23708187[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2646" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23708187">Carvill et al. (2013)</a> concluded that epileptic encephalopathy should be part of the phenotypic spectrum associated with SYNGAP1 mutations. These patients were identified from a large cohort of 500 patients with epileptic encephalopathy who underwent targeted sequencing of candidate genes. SYNGAP1 mutations accounted for 1% of cases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23708187" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#4" class="mim-tip-reference" title="Clement, J. P., Aceti, M., Creson, T. K., Ozkan, E. D., Shi, Y., Reish, N. J., Almonte, A. G., Miller, B. H., Wiltgen, B. J., Miller, C. A., Xu, X., Rumbaugh, G. <strong>Pathogenic SYNGAP1 mutations impair cognitive development by disrupting maturation of dendritic spine synapses.</strong> Cell 151: 709-723, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23141534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23141534</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23141534[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.cell.2012.08.045" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23141534">Clement et al. (2012)</a> found that haploinsufficiency for Syngap1 in mice accelerated the maturation of glutamatergic synapses in the hippocampus during the first few weeks of neonatal hippocampal development. Dendritic spines in pyramidal neurons grew larger in the mutant mice compared to wildtype mice during this critical developmental period, and the changes persisted into adulthood. There was a disruption in spine head size, with more mushroom-type spines and fewer stubby spines, the spine motility rates were decreased, and there were spine signaling abnormalities. These changes were accompanied by premature acquisition of functional AMPA receptors in the synapses. Syngap1 haploinsufficiency altered disrupted excitatory/inhibitory balance in the hippocampus, with increased excitation and increased seizure susceptibility. Changes occurred in neural networks that support cognition and behavior, such as the hippocampus, and these effects were linked to lifelong intellectual disability and impaired memory. These studies provided a neurophysiologic mechanism linking abnormal glutamatergic synapse maturation during development to enduring abnormalities in behaviors indicative of neurodevelopmental disorders in humans. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23141534" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a female patient with nonsyndromic intellectual developmental disorder (MRD5; <a href="/entry/612621">612621</a>), <a href="#7" class="mim-tip-reference" title="Hamdan, F. F., Gauthier, J., Spiegelman, D., Noreau, A., Yang, Y., Pellerin, S., Dobrzeniecka, S., Cote, M., Perreault-Linck, E., Carmant, L., D'Anjou, G., Fombonne, E., and 13 others. <strong>Mutations in SYNGAP1 in autosomal nonsyndromic mental retardation.</strong> New Eng. J. Med. 360: 599-605, 2009. Note: Erratum: New Eng. J. Med. 361: 1814 only, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19196676/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19196676</a>] [<a href="https://doi.org/10.1056/NEJMoa0805392" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19196676">Hamdan et al. (2009)</a> identified a de novo heterozygous 1735C-T transition in the SYNGAP1 gene, resulting in an arg579-to-ter (R579X) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19196676" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a female patient with nonsyndromic intellectual developmental disorder (MRD5; <a href="/entry/612621">612621</a>), <a href="#7" class="mim-tip-reference" title="Hamdan, F. F., Gauthier, J., Spiegelman, D., Noreau, A., Yang, Y., Pellerin, S., Dobrzeniecka, S., Cote, M., Perreault-Linck, E., Carmant, L., D'Anjou, G., Fombonne, E., and 13 others. <strong>Mutations in SYNGAP1 in autosomal nonsyndromic mental retardation.</strong> New Eng. J. Med. 360: 599-605, 2009. Note: Erratum: New Eng. J. Med. 361: 1814 only, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19196676/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19196676</a>] [<a href="https://doi.org/10.1056/NEJMoa0805392" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19196676">Hamdan et al. (2009)</a> identified a de novo heterozygous 1-bp deletion (2438delT) in the SYNGAP1 gene, resulting in a frameshift and premature termination. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19196676" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2151161019 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2151161019;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2151161019" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs2151161019" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000032868" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032868" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032868</a>
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<p>In a boy (patient 16) with intellectual developmental disorder with epilepsy, sleep disturbances, no speech, and no dysmorphic features (MRD5; <a href="/entry/612621">612621</a>), <a href="#5" class="mim-tip-reference" title="de Ligt, J., Willemsen, M. H., van Bon, B. W. M., Kleefstra, T., Yntema, H. G., Kroes, T., Vulto-van Silfhout, A. T., Koolen, D. A., de Vries, P., Gilissen, C., del Rosario, M., Hoischen, A., Scheffer, H., de Vries, B. B. A., Brunner, H. G., Veltman, J. A., Vissers, L. E. L. M. <strong>Diagnostic exome sequencing in persons with severe intellectual disability.</strong> New Eng. J. Med. 367: 1921-1929, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23033978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23033978</a>] [<a href="https://doi.org/10.1056/NEJMoa1206524" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23033978">de Ligt et al. (2012)</a> identified a de novo heterozygous splice site mutation in the SYNGAP1 gene (501-1G-A), likely resulting in exon skipping. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23033978" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 5</strong>
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SYNGAP1, 1-BP DEL, 2677C
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1581995953 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1581995953;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1581995953" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1581995953" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000034345" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000034345" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000034345</a>
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<p>In an 8-month-old girl with intellectual developmental disorder with well-controlled epilepsy and acquired microcephaly (MRD5; <a href="/entry/612621">612621</a>), <a href="#6" class="mim-tip-reference" title="Hamdan, F. F., Daoud, H., Piton, A., Gauthier, J., Dobrzeniecka, S., Krebs, M.-O., Joober, R., Lacaille, J.-C., Nadeau, A., Milunsky, J. M., Wang, Z., Carmant, L., Mottron, L., Beauchamp, M. H., Rouleau, G. A., Michaud, J. L. <strong>De novo SYNGAP1 mutations in nonsyndromic intellectual disability and autism.</strong> Biol. Psychiat. 69: 898-901, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21237447/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21237447</a>] [<a href="https://doi.org/10.1016/j.biopsych.2010.11.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21237447">Hamdan et al. (2011)</a> identified a de novo heterozygous 1-bp deletion (2677delC) in the SYNGAP1 gene, resulting in a frameshift and premature termination (Q893Rfs). Brain imaging was normal. The mutation was not found in 380 control individuals. The child also showed behavioral abnormalities and mood problems. She was 1 of 3 patients with a SYNGAP1 mutation identified from a larger cohort of 60 patients with nonsyndromic intellectual disability. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21237447" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 5</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1554121970 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1554121970;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1554121970" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1554121970" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000034346 OR RCV001260864 OR RCV003441726" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000034346, RCV001260864, RCV003441726" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000034346...</a>
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<p>In a 13-year-old boy with intellectual developmental disorder with autistic features (MRD5; <a href="/entry/612621">612621</a>), <a href="#6" class="mim-tip-reference" title="Hamdan, F. F., Daoud, H., Piton, A., Gauthier, J., Dobrzeniecka, S., Krebs, M.-O., Joober, R., Lacaille, J.-C., Nadeau, A., Milunsky, J. M., Wang, Z., Carmant, L., Mottron, L., Beauchamp, M. H., Rouleau, G. A., Michaud, J. L. <strong>De novo SYNGAP1 mutations in nonsyndromic intellectual disability and autism.</strong> Biol. Psychiat. 69: 898-901, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21237447/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21237447</a>] [<a href="https://doi.org/10.1016/j.biopsych.2010.11.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21237447">Hamdan et al. (2011)</a> identified a de novo heterozygous G-to-A transition in intron 13 of the SYNGAP1 gene (2294+1G-A) that was shown to cause the skipping of exon 13 and premature termination (Glu706LeufsTer38). The mutation was not found in 380 controls. The child also showed behavioral abnormalities and mood problems. He was 1 of 3 patients with a SYNGAP1 mutation identified from a larger cohort of 60 patients with nonsyndromic intellectual disability, including 30 with autistic spectrum disorders. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21237447" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0007 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 5</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1581987445 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1581987445;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1581987445" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1581987445" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000034347" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000034347" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000034347</a>
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<p>In a 3.5-year-old boy of European descent with intellectual developmental disorder with epilepsy and autism (MRD5; <a href="/entry/612621">612621</a>), <a href="#1" class="mim-tip-reference" title="Berryer, M. H., Hamdan, F. F., Klitten, L. L., Moller, R. S., Carmant, L., Schwartzentruber, J., Patry, L., Dobrzeniecka, S., Rochefort, D., Neugnot-Cerioli, M., Lacaille, J.-C., Niu, Z., and 15 others. <strong>Mutations in SYNGAP1 cause intellectual disability, autism, and a specific form of epilepsy by inducing haploinsufficiency.</strong> Hum. Mutat. 34: 385-394, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23161826/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23161826</a>] [<a href="https://doi.org/10.1002/humu.22248" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23161826">Berryer et al. (2013)</a> identified a de novo heterozygous 1084T-C transition in the SYNGAP1 gene, resulting in a trp362-to-arg (W362R) substitution at a conserved residue in the C2 domain. The mutation was not found in 570 controls or in several large SNP or exome databases. The mutant protein was not detected in neuronal cells transfected with the mutation, suggesting decreased stability. Studies in cortical pyramidal neurons showed that the missense mutation was unable to suppress activity-mediated ERK (<a href="/entry/176872">176872</a>), consistent with a loss of protein function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23161826" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0008 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 5</strong>
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SYNGAP1, PRO562LEU
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs397514670 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397514670;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs397514670" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs397514670" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000034348 OR RCV000254832 OR RCV000623832 OR RCV001265525 OR RCV003156067" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000034348, RCV000254832, RCV000623832, RCV001265525, RCV003156067" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000034348...</a>
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<p>In a 4-year-old girl of European ancestry with intellectual developmental disorder with autism (MRD5; <a href="/entry/612621">612621</a>), <a href="#1" class="mim-tip-reference" title="Berryer, M. H., Hamdan, F. F., Klitten, L. L., Moller, R. S., Carmant, L., Schwartzentruber, J., Patry, L., Dobrzeniecka, S., Rochefort, D., Neugnot-Cerioli, M., Lacaille, J.-C., Niu, Z., and 15 others. <strong>Mutations in SYNGAP1 cause intellectual disability, autism, and a specific form of epilepsy by inducing haploinsufficiency.</strong> Hum. Mutat. 34: 385-394, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23161826/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23161826</a>] [<a href="https://doi.org/10.1002/humu.22248" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23161826">Berryer et al. (2013)</a> identified a de novo heterozygous 1685C-T transition in the SYNGAP1 gene, resulting in a pro562-to-leu (P562L) substitution at a conserved residue in the GAP domain. Pro562 is located below the presumed RAS/RAP binding groove in a peptide segment connecting 2 alpha-helices, and the substitution may cause steric clashes and destablization of the protein. The mutation was not found in 570 controls or in several large SNP or exome databases. The mutant protein was not detected in neuronal cells transfected with the mutation, suggesting decreased stability. Studies in cortical pyramidal neurons showed that the missense mutation was unable to suppress activity-mediated ERK (<a href="/entry/176872">176872</a>), consistent with a loss of protein function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23161826" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0009 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 5</strong>
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<p>In a 26-year-old woman with intellectual developmental disorder with autistic features and epileptic encephalopathy (MRD5; <a href="/entry/612621">612621</a>), <a href="#2" class="mim-tip-reference" title="Carvill, G. L., Heavin, S. B., Yendle, S. C., McMahon, J. M., O'Roak, B. J., Cook, J., Khan, A., Dorschner, M. O., Weaver, M., Calvert, S., Malone, S., Wallace, G., and 22 others. <strong>Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.</strong> Nature Genet. 45: 825-830, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23708187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23708187</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23708187[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2646" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23708187">Carvill et al. (2013)</a> identified a de novo heterozygous trp257-to-ter mutation in the SYNGAP1 gene. The patient had delayed development, onset of atypical absence seizures at age 3 years, followed by atonic seizures, focal dyscognitive seizures, and myoclonic jerks associated with EEG abnormalities. She showed cognitive regression after seizure onset. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23708187" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs397514741 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397514741;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs397514741" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs397514741" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000054513 OR RCV000599367 OR RCV001265523" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000054513, RCV000599367, RCV001265523" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000054513...</a>
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<p>In a 7-year-old girl with intellectual developmental disorder with autistic features and epileptic encephalopathy (MRD5; <a href="/entry/612621">612621</a>), <a href="#2" class="mim-tip-reference" title="Carvill, G. L., Heavin, S. B., Yendle, S. C., McMahon, J. M., O'Roak, B. J., Cook, J., Khan, A., Dorschner, M. O., Weaver, M., Calvert, S., Malone, S., Wallace, G., and 22 others. <strong>Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.</strong> Nature Genet. 45: 825-830, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23708187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23708187</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23708187[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2646" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23708187">Carvill et al. (2013)</a> identified a de novo heterozygous arg143-to-ter (R143X) mutation in the SYNGAP1 gene. The patient had delayed development, onset of absence seizures at age 10 months, and myoclonic jerks associated with EEG abnormalities. She showed cognitive regression after seizure onset. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23708187" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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Berryer, M. H., Hamdan, F. F., Klitten, L. L., Moller, R. S., Carmant, L., Schwartzentruber, J., Patry, L., Dobrzeniecka, S., Rochefort, D., Neugnot-Cerioli, M., Lacaille, J.-C., Niu, Z., and 15 others.
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<strong>Mutations in SYNGAP1 cause intellectual disability, autism, and a specific form of epilepsy by inducing haploinsufficiency.</strong>
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Hum. Mutat. 34: 385-394, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23161826/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23161826</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23161826" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/humu.22248" target="_blank">Full Text</a>]
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Carvill, G. L., Heavin, S. B., Yendle, S. C., McMahon, J. M., O'Roak, B. J., Cook, J., Khan, A., Dorschner, M. O., Weaver, M., Calvert, S., Malone, S., Wallace, G., and 22 others.
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<strong>Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.</strong>
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Nature Genet. 45: 825-830, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23708187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23708187</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23708187[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23708187" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng.2646" target="_blank">Full Text</a>]
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<a id="Chen1998" class="mim-anchor"></a>
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Chen, H.-J., Rojas-Soto, M., Oguni, A., Kennedy, M. B.
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<strong>A synaptic Ras-GTPase activating protein (p135 SynGAP) inhibited by CaM kinase II.</strong>
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Neuron 20: 895-904, 1998. Note: Erratum: Neuron 33: 151 only, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9620694/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9620694</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9620694" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0896-6273(00)80471-7" target="_blank">Full Text</a>]
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Clement, J. P., Aceti, M., Creson, T. K., Ozkan, E. D., Shi, Y., Reish, N. J., Almonte, A. G., Miller, B. H., Wiltgen, B. J., Miller, C. A., Xu, X., Rumbaugh, G.
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<strong>Pathogenic SYNGAP1 mutations impair cognitive development by disrupting maturation of dendritic spine synapses.</strong>
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Cell 151: 709-723, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23141534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23141534</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23141534[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23141534" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.cell.2012.08.045" target="_blank">Full Text</a>]
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de Ligt, J., Willemsen, M. H., van Bon, B. W. M., Kleefstra, T., Yntema, H. G., Kroes, T., Vulto-van Silfhout, A. T., Koolen, D. A., de Vries, P., Gilissen, C., del Rosario, M., Hoischen, A., Scheffer, H., de Vries, B. B. A., Brunner, H. G., Veltman, J. A., Vissers, L. E. L. M.
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<strong>Diagnostic exome sequencing in persons with severe intellectual disability.</strong>
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New Eng. J. Med. 367: 1921-1929, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23033978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23033978</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23033978" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1056/NEJMoa1206524" target="_blank">Full Text</a>]
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Hamdan, F. F., Daoud, H., Piton, A., Gauthier, J., Dobrzeniecka, S., Krebs, M.-O., Joober, R., Lacaille, J.-C., Nadeau, A., Milunsky, J. M., Wang, Z., Carmant, L., Mottron, L., Beauchamp, M. H., Rouleau, G. A., Michaud, J. L.
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<strong>De novo SYNGAP1 mutations in nonsyndromic intellectual disability and autism.</strong>
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Biol. Psychiat. 69: 898-901, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21237447/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21237447</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21237447" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.biopsych.2010.11.015" target="_blank">Full Text</a>]
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Hamdan, F. F., Gauthier, J., Spiegelman, D., Noreau, A., Yang, Y., Pellerin, S., Dobrzeniecka, S., Cote, M., Perreault-Linck, E., Carmant, L., D'Anjou, G., Fombonne, E., and 13 others.
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<strong>Mutations in SYNGAP1 in autosomal nonsyndromic mental retardation.</strong>
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New Eng. J. Med. 360: 599-605, 2009. Note: Erratum: New Eng. J. Med. 361: 1814 only, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19196676/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19196676</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19196676" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1056/NEJMoa0805392" target="_blank">Full Text</a>]
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Oh, J. S., Chen, H.-J., Rojas-Soto, M., Oguni, A., Kennedy, M. B.
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<strong>Erratum.</strong>
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Neuron 33: 151 only, 2002.
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Rumbaugh, G., Adams, J. P., Kim, J. H., Huganir, R. L.
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<strong>SynGAP regulates synaptic strength and mitogen-activated protein kinases in cultured neurons.</strong>
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Proc. Nat. Acad. Sci. 103: 4344-4351, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16537406/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16537406</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16537406[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16537406" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.0600084103" target="_blank">Full Text</a>]
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<a id="10" class="mim-anchor"></a>
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<a id="Tomoda2004" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tomoda, T., Kim, J. H., Zhan, C., Hatten, M. E.
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<strong>Role of Unc51.1 and its binding partners in CNS axon outgrowth.</strong>
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Genes Dev. 18: 541-558, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15014045/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15014045</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15014045[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15014045" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1101/gad.1151204" target="_blank">Full Text</a>]
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Cassandra L. Kniffin - updated : 8/15/2013
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 3/28/2013<br>Ada Hamosh - updated : 2/12/2013<br>Cassandra L. Kniffin - updated : 2/11/2009<br>Patricia A. Hartz - updated : 6/5/2006<br>Patricia A. Hartz - updated : 5/12/2004<br>Paul J. Converse - updated : 2/28/2002
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Creation Date:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Sheryl A. Jankowski : 12/24/1998
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carol : 04/04/2022
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carol : 09/24/2013<br>carol : 8/19/2013<br>ckniffin : 8/15/2013<br>carol : 4/1/2013<br>ckniffin : 3/28/2013<br>carol : 2/12/2013<br>carol : 2/12/2013<br>terry : 7/27/2012<br>wwang : 2/7/2011<br>wwang : 2/16/2009<br>ckniffin : 2/11/2009<br>mgross : 6/6/2006<br>terry : 6/5/2006<br>mgross : 5/12/2004<br>carol : 2/28/2002<br>psherman : 12/3/1999<br>psherman : 1/4/1999
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<strong>*</strong> 603384
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SYNAPTIC RAS-GTPase-ACTIVATING PROTEIN 1; SYNGAP1
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GTPase-ACTIVATING PROTEIN, RAS, SYNAPTIC, 135-KD, RAT, HOMOLOG OF<br />
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RAS-GTPase-ACTIVATING PROTEIN, SYNAPTIC, 135-KD, RAT, HOMOLOG OF<br />
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SYNAPTIC RAS-GTPase-ACTIVATING PROTEIN, 135-KD, RAT, HOMOLOG OF<br />
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SYNGAP, p135, RAT, HOMOLOG OF; SYNGAP
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<strong><em>HGNC Approved Gene Symbol: SYNGAP1</em></strong>
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Cytogenetic location: 6p21.32
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Genomic coordinates <span class="small">(GRCh38)</span> : 6:33,418,167-33,453,689 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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<strong>Gene-Phenotype Relationships</strong>
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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6p21.32
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Intellectual developmental disorder, autosomal dominant 5
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612621
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Autosomal dominant
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<span class="mim-font">
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3
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<strong>TEXT</strong>
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<strong>Description</strong>
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<p>The SYNGAP1 gene encodes a brain-specific synaptic Ras GTP-ase activating protein that is largely localized to dendritic spines in neocortical pyramidal neurons, where it suppresses signaling pathways linked to NMDA receptor (NMDAR)-mediated synaptic plasticity and AMPA receptor (AMPAR) membrane insertion (summary by Clement et al., 2012 and Berryer et al., 2013). </p>
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<strong>Cloning and Expression</strong>
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<p>Calmodulin-dependent protein kinase II (CaMKII; e.g., 114078) is activated in hippocampal neurons by the rise in intracellular calcium that follows stimulation of NMDA receptors (e.g., 138249). CaMKII is concentrated in the postsynaptic density (PSD), a complex of proteins that colocalize with NMDA receptors at synapses. To determine the targets of CaMKII at the postsynaptic site, Chen et al. (1998) sequenced tryptic peptides from rat forebrain PSDs, performed RT-PCR using degenerate primers based on the peptide sequences, and screened a rat brain cDNA library with the PCR products. They isolated cDNAs encoding a novel synaptic Ras-GTPase-activating protein, p135-Syngap, which is a major component of the PSD. The deduced p135-Syngap protein contains a putative pleckstrin homology domain in the N-terminal segment; a region showing partial identity to the C2 domain of p120-RASGAP; a RasGAP motif; a proline-rich, putative SH3 domain-binding site; 29 consensus sites for phosphorylation by CaMKII; and a C-terminal consensus sequence that can bind to the scaffold protein PSD95 (602887). The authors found that p135-Syngap is most highly expressed in the brain, localizes to glutamatergic synapses, and forms a complex with PSD95. Chen et al. (1998) also isolated cDNAs representing alternatively spliced p135-Syngap transcripts, 1 of which encodes a variant p135-Syngap protein lacking the C-terminal consensus site. Oh et al. (2002) corrected the observation of Chen et al. (1998) regarding the activity of p135-SYNGAP and stated that the Ras-GTPase-activating protein is phosphorylated, rather than inhibited, by CaMKII. </p><p>The sequence of a human cosmid clone from chromosome 6 that contains the first 2 exons of a human homolog of rat p135-Syngap, named SYNGAP1, has been deposited in GenBank (AL021366).</p><p>SYNGAP1 is expressed throughout the forebrain, with particularly high levels in the hippocampus. In mice, Clement et al. (2012) found peak expression of the Syngap1 gene in the hippocampus around postnatal day 14. </p>
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<strong>Gene Function</strong>
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<p>Tomoda et al. (2004) found that SynGAP, a negative regulator of Ras (190020), was expressed within axons and growth cones of developing mouse granule cells. Overexpression of SynGAP blocked neurite outgrowth by a mechanism that involved a Ras-like GTPase cascade. Using a yeast 2-hybrid assay, Tomoda et al. (2004) determined that the C terminus of mouse Unc51.1 (603168) bound the C terminus of SynGAP. Both proteins localized to the membrane fraction of mouse cerebral cortex lysates. Using a reporter assay, Tomoda et al. (2004) found that Unc51.1 inhibited SynGAP through its kinase activity. They concluded that Unc51.1 and SynGAP function cooperatively in axon formation. </p><p>Rumbaugh et al. (2006) found that SynGAP1 regulated AMPA receptor (AMPAR; see 138248) trafficking, excitatory synaptic transmission, and the number of silent synapses (i.e., excitatory synapses that lack functional AMPARs) in rodent hippocampal and cortical cultured neurons. The results suggested that SynGAP1 affects these characteristics by regulating the MAP kinase (see MAPK1; 176948) signaling pathway. </p>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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<p>In 3 of 94 patients with nonsyndromic intellectual developmental disorder-5 (MRD5; 612621), Hamdan et al. (2009) identified 3 different de novo heterozygous truncating mutations in the SYNGAP1 gene (603384.0001-603384.0003). All patients showed global developmental delay with delayed motor development, hypotonia, moderate to severe mental retardation, and severe language impairment without dysmorphic features. Nonpathologic missense variants in the SYNGAP1 gene were identified in 9 of 142 individuals with autism spectrum disorders and 6 of 143 individuals with schizophrenia. </p><p>In 3 of 60 patients with nonsyndromic intellectual disability, including 30 with autism spectrum disorder and 9 with epilepsy, Hamdan et al. (2011) identified de novo heterozygous truncating mutations in the SYNGAP1 gene (see, e.g., 603384.0005 and 603384.0006). The children also showed behavioral abnormalities and mood problems. Two had well-controlled epilepsy and acquired microcephaly, and 1 had autism, thus expanding the phenotypic spectrum associated with SYNGAP1 mutations. </p><p>Berryer et al. (2013) identified 5 different SYNGAP1 mutations (see, e.g., 603384.0007 and 603384.0008) in 5 unrelated patients with nonsyndromic intellectual disability. There were 3 truncating mutations and 2 missense mutations. These patients were identified by targeted sequencing of the SYNGAP1 gene in several cohorts including a total of 34 patients with nonsyndromic intellectual disability. Of the 5 with mutations, 4 had early-childhood onset of epilepsy, 3 had autism, and 3 had behavioral abnormalities. There were no notable dysmorphic features or structural brain abnormalities. Four of the mutations occurred de novo; 1 was inherited from a mildly affected parent who was mosaic for the mutation. None of the mutant proteins were detected in neuronal cells transfected with the mutations, suggesting decreased stability, even of the missense mutations. Studies in cortical pyramidal neurons showed that the missense mutations were unable to suppress activity-mediated ERK (176872), consistent with a loss of protein function. </p><p>Carvill et al. (2013) reported 5 unrelated patients with mental retardation and epileptic encephalopathy associated with heterozygous truncating mutations in the SYNGAP1 gene (see, e.g., 603384.0009-603384.0010). All had delayed development and onset of various seizure types between 6 months and 3 years that were associated with multiple EEG abnormalities and cognitive regression. Four patients had autistic spectrum disorder. In 2 patients, the mutations occurred de novo; in the other 3 patients, DNA from one or both parents was not available for study. Carvill et al. (2013) concluded that epileptic encephalopathy should be part of the phenotypic spectrum associated with SYNGAP1 mutations. These patients were identified from a large cohort of 500 patients with epileptic encephalopathy who underwent targeted sequencing of candidate genes. SYNGAP1 mutations accounted for 1% of cases. </p>
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<strong>Animal Model</strong>
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<span class="mim-text-font">
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<p>Clement et al. (2012) found that haploinsufficiency for Syngap1 in mice accelerated the maturation of glutamatergic synapses in the hippocampus during the first few weeks of neonatal hippocampal development. Dendritic spines in pyramidal neurons grew larger in the mutant mice compared to wildtype mice during this critical developmental period, and the changes persisted into adulthood. There was a disruption in spine head size, with more mushroom-type spines and fewer stubby spines, the spine motility rates were decreased, and there were spine signaling abnormalities. These changes were accompanied by premature acquisition of functional AMPA receptors in the synapses. Syngap1 haploinsufficiency altered disrupted excitatory/inhibitory balance in the hippocampus, with increased excitation and increased seizure susceptibility. Changes occurred in neural networks that support cognition and behavior, such as the hippocampus, and these effects were linked to lifelong intellectual disability and impaired memory. These studies provided a neurophysiologic mechanism linking abnormal glutamatergic synapse maturation during development to enduring abnormalities in behaviors indicative of neurodevelopmental disorders in humans. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>10 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 5</strong>
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</span>
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SYNGAP1, LYS138TER
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<br />
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SNP: rs121918315,
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ClinVar: RCV000006764
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<span class="mim-text-font">
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<p>In a female patient with nonsyndromic intellectual developmental disorder (MRD5; 612621), Hamdan et al. (2009) identified a de novo heterozygous 412A-T transversion in the SYNGAP1 gene, resulting in a lys138-to-ter (K138X) substitution. </p>
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<span class="mim-font">
|
|
<strong>.0002 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 5</strong>
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</span>
|
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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SYNGAP1, ARG579TER
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<br />
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SNP: rs121918316,
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ClinVar: RCV000006765, RCV000255371, RCV002399311
|
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|
</span>
|
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a female patient with nonsyndromic intellectual developmental disorder (MRD5; 612621), Hamdan et al. (2009) identified a de novo heterozygous 1735C-T transition in the SYNGAP1 gene, resulting in an arg579-to-ter (R579X) substitution. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
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<span class="mim-font">
|
|
<strong>.0003 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 5</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
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SYNGAP1, 1-BP DEL, 2438T
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<br />
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SNP: rs397515320,
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ClinVar: RCV000006766, RCV001588803
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a female patient with nonsyndromic intellectual developmental disorder (MRD5; 612621), Hamdan et al. (2009) identified a de novo heterozygous 1-bp deletion (2438delT) in the SYNGAP1 gene, resulting in a frameshift and premature termination. </p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
SYNGAP1, c.501-1G-A
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<br />
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SNP: rs2151161019,
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|
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|
|
ClinVar: RCV000032868
|
|
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|
|
</span>
|
|
</div>
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|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy (patient 16) with intellectual developmental disorder with epilepsy, sleep disturbances, no speech, and no dysmorphic features (MRD5; 612621), de Ligt et al. (2012) identified a de novo heterozygous splice site mutation in the SYNGAP1 gene (501-1G-A), likely resulting in exon skipping. </p>
|
|
</span>
|
|
</div>
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<div>
|
|
<br />
|
|
</div>
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|
|
</div>
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|
<div>
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|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SYNGAP1, 1-BP DEL, 2677C
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|
|
<br />
|
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|
|
SNP: rs1581995953,
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|
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|
|
ClinVar: RCV000034345
|
|
|
|
|
|
</span>
|
|
</div>
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|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an 8-month-old girl with intellectual developmental disorder with well-controlled epilepsy and acquired microcephaly (MRD5; 612621), Hamdan et al. (2011) identified a de novo heterozygous 1-bp deletion (2677delC) in the SYNGAP1 gene, resulting in a frameshift and premature termination (Q893Rfs). Brain imaging was normal. The mutation was not found in 380 control individuals. The child also showed behavioral abnormalities and mood problems. She was 1 of 3 patients with a SYNGAP1 mutation identified from a larger cohort of 60 patients with nonsyndromic intellectual disability. </p>
|
|
</span>
|
|
</div>
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<div>
|
|
<br />
|
|
</div>
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|
|
</div>
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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<div>
|
|
<span class="mim-text-font">
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|
|
|
SYNGAP1, IVS13DS, G-A, +1
|
|
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|
|
<br />
|
|
|
|
SNP: rs1554121970,
|
|
|
|
|
|
|
|
ClinVar: RCV000034346, RCV001260864, RCV003441726
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 13-year-old boy with intellectual developmental disorder with autistic features (MRD5; 612621), Hamdan et al. (2011) identified a de novo heterozygous G-to-A transition in intron 13 of the SYNGAP1 gene (2294+1G-A) that was shown to cause the skipping of exon 13 and premature termination (Glu706LeufsTer38). The mutation was not found in 380 controls. The child also showed behavioral abnormalities and mood problems. He was 1 of 3 patients with a SYNGAP1 mutation identified from a larger cohort of 60 patients with nonsyndromic intellectual disability, including 30 with autistic spectrum disorders. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SYNGAP1, TRP362ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1581987445,
|
|
|
|
|
|
|
|
ClinVar: RCV000034347
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 3.5-year-old boy of European descent with intellectual developmental disorder with epilepsy and autism (MRD5; 612621), Berryer et al. (2013) identified a de novo heterozygous 1084T-C transition in the SYNGAP1 gene, resulting in a trp362-to-arg (W362R) substitution at a conserved residue in the C2 domain. The mutation was not found in 570 controls or in several large SNP or exome databases. The mutant protein was not detected in neuronal cells transfected with the mutation, suggesting decreased stability. Studies in cortical pyramidal neurons showed that the missense mutation was unable to suppress activity-mediated ERK (176872), consistent with a loss of protein function. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SYNGAP1, PRO562LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs397514670,
|
|
|
|
|
|
|
|
ClinVar: RCV000034348, RCV000254832, RCV000623832, RCV001265525, RCV003156067
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 4-year-old girl of European ancestry with intellectual developmental disorder with autism (MRD5; 612621), Berryer et al. (2013) identified a de novo heterozygous 1685C-T transition in the SYNGAP1 gene, resulting in a pro562-to-leu (P562L) substitution at a conserved residue in the GAP domain. Pro562 is located below the presumed RAS/RAP binding groove in a peptide segment connecting 2 alpha-helices, and the substitution may cause steric clashes and destablization of the protein. The mutation was not found in 570 controls or in several large SNP or exome databases. The mutant protein was not detected in neuronal cells transfected with the mutation, suggesting decreased stability. Studies in cortical pyramidal neurons showed that the missense mutation was unable to suppress activity-mediated ERK (176872), consistent with a loss of protein function. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SYNGAP1, TRP267TER
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000054514
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 26-year-old woman with intellectual developmental disorder with autistic features and epileptic encephalopathy (MRD5; 612621), Carvill et al. (2013) identified a de novo heterozygous trp257-to-ter mutation in the SYNGAP1 gene. The patient had delayed development, onset of atypical absence seizures at age 3 years, followed by atonic seizures, focal dyscognitive seizures, and myoclonic jerks associated with EEG abnormalities. She showed cognitive regression after seizure onset. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SYNGAP1, ARG143TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs397514741,
|
|
|
|
|
|
|
|
ClinVar: RCV000054513, RCV000599367, RCV001265523
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 7-year-old girl with intellectual developmental disorder with autistic features and epileptic encephalopathy (MRD5; 612621), Carvill et al. (2013) identified a de novo heterozygous arg143-to-ter (R143X) mutation in the SYNGAP1 gene. The patient had delayed development, onset of absence seizures at age 10 months, and myoclonic jerks associated with EEG abnormalities. She showed cognitive regression after seizure onset. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Berryer, M. H., Hamdan, F. F., Klitten, L. L., Moller, R. S., Carmant, L., Schwartzentruber, J., Patry, L., Dobrzeniecka, S., Rochefort, D., Neugnot-Cerioli, M., Lacaille, J.-C., Niu, Z., and 15 others.
|
|
<strong>Mutations in SYNGAP1 cause intellectual disability, autism, and a specific form of epilepsy by inducing haploinsufficiency.</strong>
|
|
Hum. Mutat. 34: 385-394, 2013.
|
|
|
|
|
|
[PubMed: 23161826]
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|
|
|
|
[Full Text: https://doi.org/10.1002/humu.22248]
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Carvill, G. L., Heavin, S. B., Yendle, S. C., McMahon, J. M., O'Roak, B. J., Cook, J., Khan, A., Dorschner, M. O., Weaver, M., Calvert, S., Malone, S., Wallace, G., and 22 others.
|
|
<strong>Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.</strong>
|
|
Nature Genet. 45: 825-830, 2013.
|
|
|
|
|
|
[PubMed: 23708187]
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|
|
[Full Text: https://doi.org/10.1038/ng.2646]
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|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chen, H.-J., Rojas-Soto, M., Oguni, A., Kennedy, M. B.
|
|
<strong>A synaptic Ras-GTPase activating protein (p135 SynGAP) inhibited by CaM kinase II.</strong>
|
|
Neuron 20: 895-904, 1998. Note: Erratum: Neuron 33: 151 only, 2002.
|
|
|
|
|
|
[PubMed: 9620694]
|
|
|
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|
|
[Full Text: https://doi.org/10.1016/s0896-6273(00)80471-7]
|
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Clement, J. P., Aceti, M., Creson, T. K., Ozkan, E. D., Shi, Y., Reish, N. J., Almonte, A. G., Miller, B. H., Wiltgen, B. J., Miller, C. A., Xu, X., Rumbaugh, G.
|
|
<strong>Pathogenic SYNGAP1 mutations impair cognitive development by disrupting maturation of dendritic spine synapses.</strong>
|
|
Cell 151: 709-723, 2012.
|
|
|
|
|
|
[PubMed: 23141534]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.cell.2012.08.045]
|
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|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
de Ligt, J., Willemsen, M. H., van Bon, B. W. M., Kleefstra, T., Yntema, H. G., Kroes, T., Vulto-van Silfhout, A. T., Koolen, D. A., de Vries, P., Gilissen, C., del Rosario, M., Hoischen, A., Scheffer, H., de Vries, B. B. A., Brunner, H. G., Veltman, J. A., Vissers, L. E. L. M.
|
|
<strong>Diagnostic exome sequencing in persons with severe intellectual disability.</strong>
|
|
New Eng. J. Med. 367: 1921-1929, 2012.
|
|
|
|
|
|
[PubMed: 23033978]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMoa1206524]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hamdan, F. F., Daoud, H., Piton, A., Gauthier, J., Dobrzeniecka, S., Krebs, M.-O., Joober, R., Lacaille, J.-C., Nadeau, A., Milunsky, J. M., Wang, Z., Carmant, L., Mottron, L., Beauchamp, M. H., Rouleau, G. A., Michaud, J. L.
|
|
<strong>De novo SYNGAP1 mutations in nonsyndromic intellectual disability and autism.</strong>
|
|
Biol. Psychiat. 69: 898-901, 2011.
|
|
|
|
|
|
[PubMed: 21237447]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.biopsych.2010.11.015]
|
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|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hamdan, F. F., Gauthier, J., Spiegelman, D., Noreau, A., Yang, Y., Pellerin, S., Dobrzeniecka, S., Cote, M., Perreault-Linck, E., Carmant, L., D'Anjou, G., Fombonne, E., and 13 others.
|
|
<strong>Mutations in SYNGAP1 in autosomal nonsyndromic mental retardation.</strong>
|
|
New Eng. J. Med. 360: 599-605, 2009. Note: Erratum: New Eng. J. Med. 361: 1814 only, 2009.
|
|
|
|
|
|
[PubMed: 19196676]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMoa0805392]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Oh, J. S., Chen, H.-J., Rojas-Soto, M., Oguni, A., Kennedy, M. B.
|
|
<strong>Erratum.</strong>
|
|
Neuron 33: 151 only, 2002.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rumbaugh, G., Adams, J. P., Kim, J. H., Huganir, R. L.
|
|
<strong>SynGAP regulates synaptic strength and mitogen-activated protein kinases in cultured neurons.</strong>
|
|
Proc. Nat. Acad. Sci. 103: 4344-4351, 2006.
|
|
|
|
|
|
[PubMed: 16537406]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0600084103]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tomoda, T., Kim, J. H., Zhan, C., Hatten, M. E.
|
|
<strong>Role of Unc51.1 and its binding partners in CNS axon outgrowth.</strong>
|
|
Genes Dev. 18: 541-558, 2004.
|
|
|
|
|
|
[PubMed: 15014045]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1101/gad.1151204]
|
|
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|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
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Cassandra L. Kniffin - updated : 8/15/2013<br>Cassandra L. Kniffin - updated : 3/28/2013<br>Ada Hamosh - updated : 2/12/2013<br>Cassandra L. Kniffin - updated : 2/11/2009<br>Patricia A. Hartz - updated : 6/5/2006<br>Patricia A. Hartz - updated : 5/12/2004<br>Paul J. Converse - updated : 2/28/2002
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Sheryl A. Jankowski : 12/24/1998
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carol : 04/04/2022<br>carol : 09/24/2013<br>carol : 8/19/2013<br>ckniffin : 8/15/2013<br>carol : 4/1/2013<br>ckniffin : 3/28/2013<br>carol : 2/12/2013<br>carol : 2/12/2013<br>terry : 7/27/2012<br>wwang : 2/7/2011<br>wwang : 2/16/2009<br>ckniffin : 2/11/2009<br>mgross : 6/6/2006<br>terry : 6/5/2006<br>mgross : 5/12/2004<br>carol : 2/28/2002<br>psherman : 12/3/1999<br>psherman : 1/4/1999
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