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Entry
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- *182530 - SOS RAS/RAC GUANINE NUCLEOTIDE EXCHANGE FACTOR 1; SOS1
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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">*182530</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="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#biochemicalFeatures">Biochemical Features</a>
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<a href="#geneFunction">Gene Function</a>
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<a href="#molecularGenetics">Molecular Genetics</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>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/182530">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 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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</li>
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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=ENSG00000115904;t=ENST00000402219" 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=6654" 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=182530" 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=ENSG00000115904;t=ENST00000402219" 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_001382394,NM_001382395,NM_005633,XM_011533064,XM_047445581,XM_047445582,XM_047445583,XM_047445584,XM_047445585,XM_047445586" 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_005633" 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=182530" 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=01681&isoform_id=01681_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/SOS1" 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/306778,6094322,6164601,15529996,20467105,62087860,62702260,62988815,119620755,119620756,119620757,119620758,158261479,194378022,311851680,767915125,1403730466,1838744767,1838744875,2217330414,2217330417,2217330419,2217330421,2217330423,2217330425,2462576336,2462576338,2462576340,2462576342,2462576344,2462576346" 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/Q07889" 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=6654" 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=ENSG00000115904;t=ENST00000402219" 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=SOS1" 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=SOS1" 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+6654" 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/SOS1" 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:6654" 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/6654" 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=chr2&hgg_gene=ENST00000402219.8&hgg_start=38981549&hgg_end=39124868&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:11187" 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:11187" 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/sos1" 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=182530[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=182530[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/SOS1/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/ENSG00000115904" 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=SOS1" 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=SOS1" 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=SOS1" 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=SOS1&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/PA36024" 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:11187" 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/FBgn0001965.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:98354" 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/SOS1#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:98354" 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/6654/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=6654" 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=WBGene00004947;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-070209-128" 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="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">
|
|
<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:6654" 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=SOS1&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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182530
|
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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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SOS RAS/RAC GUANINE NUCLEOTIDE EXCHANGE FACTOR 1; SOS1
|
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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">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
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</p>
|
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</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
SON OF SEVENLESS, DROSOPHILA, HOMOLOG 1<br />
|
|
SOS1 GUANINE NUCLEOTIDE EXCHANGE FACTOR
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
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<div>
|
|
<br />
|
|
</div>
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</div>
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<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=SOS1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">SOS1</a></em></strong>
|
|
</span>
|
|
</p>
|
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</div>
|
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/2/200?start=-3&limit=10&highlight=200">2p22.1</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr2:38981549-39124868&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'})">2:38,981,549-39,124,868</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
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|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<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">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=135300,610733" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/2/200?start=-3&limit=10&highlight=200">
|
|
2p22.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Fibromatosis, gingival, 1
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/135300"> 135300 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
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|
|
|
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|
|
</tr>
|
|
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|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Noonan syndrome 4
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/610733"> 610733 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
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<p>RAS genes (e.g., <a href="/entry/190020">190020</a>) encode membrane-bound guanine nucleotide-binding proteins that function in the transduction of signals that control cell growth and differentiation. Binding of GTP activates RAS proteins, and subsequent hydrolysis of the bound GTP to GDP and phosphate inactivates signaling by these proteins. GTP binding can be catalyzed by guanine nucleotide exchange factors for RAS, and GTP hydrolysis can be accelerated by GTPase-activating proteins (GAPs). The first exchange factor to be identified for RAS was the S. cerevisiae CDC25 gene product. Genetic analysis indicated that CDC25 is essential for activation of RAS proteins. In Drosophila, the protein encoded by the 'son of sevenless' gene (Sos) contains a domain that shows sequence similarity with the catalytic domain of CDC25. Sos may act as a positive regulator of RAS by promoting guanine nucleotide exchange.</p>
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<p><a href="#1" class="mim-tip-reference" title="Bowtell, D., Fu, P., Simon, M. A., Senior, P. <strong>Identification of murine homologues of the Drosophila Son of sevenless gene: potential activators of ras.</strong> Proc. Nat. Acad. Sci. 89: 6511-6515, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1631150/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1631150</a>] [<a href="https://doi.org/10.1073/pnas.89.14.6511" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1631150">Bowtell et al. (1992)</a> isolated 2 cDNAs, designated Sos1 and Sos2 (<a href="/entry/601247">601247</a>), from a mouse eye library by screening with a probe from the Drosophila Sos gene. Sos1 encodes a predicted 1,336-amino acid protein which is 67% identical to the partial Sos2 sequence. Both Sos1 and Sos2 have an overall amino acid identity of 45% with the Drosophila Sos gene product. Northern blots showed that both genes are expressed in a wide variety of tissues and cell lines. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1631150" 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="Chardin, P., Camonis, J. H., Gale, N. W., Van Aelst, L., Schlessinger, J., Wigler, M. H., Bar-Sagi, D. <strong>Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2.</strong> Science 260: 1338-1343, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8493579/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8493579</a>] [<a href="https://doi.org/10.1126/science.8493579" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8493579">Chardin et al. (1993)</a> isolated a human cDNA that encodes a widely expressed 1,333-amino acid protein that is closely related to the product of the Drosophila Sos gene and nearly identical to the mouse Sos1 gene product. A fragment of the human gene encoding the CDC25-related domain complemented loss of CDC25 function in yeast. The same domain of the human gene specifically stimulated guanine nucleotide exchange on mammalian RAS proteins in vitro. This and other evidence indicated to <a href="#2" class="mim-tip-reference" title="Chardin, P., Camonis, J. H., Gale, N. W., Van Aelst, L., Schlessinger, J., Wigler, M. H., Bar-Sagi, D. <strong>Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2.</strong> Science 260: 1338-1343, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8493579/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8493579</a>] [<a href="https://doi.org/10.1126/science.8493579" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8493579">Chardin et al. (1993)</a> that SOS1 is a guanine nucleotide exchange factor for RAS in the human. Further studies suggested that the coupling of receptor tyrosine kinases to RAS signaling is mediated by a molecular complex consisting of growth factor receptor-bound protein-2 (<a href="/entry/108355">108355</a>) and SOS1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8493579" 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="#5" class="mim-tip-reference" title="Hart, T. C., Zhang, Y., Gorry, M. C., Hart, P. S., Cooper, M., Marazita, M. L., Marks, J. M., Cortelli, J. R., Pallos, D. <strong>A mutation in the SOS1 gene causes hereditary gingival fibromatosis type 1.</strong> Am. J. Hum. Genet. 70: 943-954, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11868160/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11868160</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11868160[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/10.1086/339689" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11868160">Hart et al. (2002)</a> determined that the SOS1 gene spans 136 kb and consists of 24 exons. Intronic sizes range from 30 bp to 53 kb. The translation initiation codon is located at nucleotides 45 to 47 of exon 2, and the open reading frame is terminated at nucleotide 492 in exon 24. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11868160" 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="#16" class="mim-tip-reference" title="Webb, G. C., Jenkins, N. A., Largaespada, D. A., Copeland, N. G., Fernandez, C. S., Bowtell, D. D. L. <strong>Mammalian homologues of the Drosophila Son of sevenless gene map to murine chromosomes 17 and 12 and to human chromosomes 2 and 14, respectively.</strong> Genomics 18: 14-19, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8276400/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8276400</a>] [<a href="https://doi.org/10.1006/geno.1993.1421" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8276400">Webb et al. (1993)</a> mapped the mouse Sos1 gene to chromosome 17E by interspecific backcross analysis and in situ hybridization. They mapped the human SOS1 gene to chromosome 2p22-p21 by in situ hybridization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8276400" 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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Proteins containing Dbl homology (DH) domains, such as SOS1, activate Rho family GTPases by functioning as specific guanine nucleotide exchange factors. All known DH domains have associated C-terminal pleckstrin homology (PH) domains that are implicated in targeting and regulatory functions. <a href="#12" class="mim-tip-reference" title="Soisson, S. M., Nimnual, A. S., Uy, M., Bar-Sagi, D., Kuriyan, J. <strong>Crystal structure of the Dbl and pleckstrin homology domains from the human Son of sevenless protein.</strong> Cell 95: 259-268, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9790532/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9790532</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81756-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9790532">Soisson et al. (1998)</a> determined the crystal structure of a fragment of the human SOS1 protein containing the DH and PH domains at 2.3-angstrom resolution. The entirely alpha-helical DH domain was unrelated in architecture to other nucleotide exchange factors. The active site of the DH domain, identified on the basis of sequence conservation and structural features, lies near the interface between the DH and PH domains. The structure suggested to the authors that ligation of the PH domain will be coupled structurally to the GTPase-binding site. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9790532" 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="Scita, G., Nordstrom, J., Carbone, R., Tenca, P., Giardina, G., Gutkind, S., Bjarnegard, M., Betsholtz, C., Di Fiore, P. P. <strong>EPS8 and E3B1 transduce signals from Ras to Rac.</strong> Nature 401: 290-293, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10499589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10499589</a>] [<a href="https://doi.org/10.1038/45822" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10499589">Scita et al. (1999)</a> showed that EPS8 (<a href="/entry/600206">600206</a>), E3B1 (<a href="/entry/603050">603050</a>), and SOS1 form a tricomplex in vivo that exhibits RAC (see <a href="/entry/602048">602048</a>)-specific guanine nucleotide exchange factor (GEF) activity in vitro. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10499589" 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>Epidermal growth factor receptor (EGFR; <a href="/entry/131550">131550</a>) is required for skin development and is implicated in epithelial tumor formation. <a href="#11" class="mim-tip-reference" title="Sibilia, M., Fleischmann, A., Behrens, A., Stingl, L., Carroll, J., Watt, F. M., Schlessinger, J., Wagner, E. F. <strong>The EGF receptor provides an essential survival signal for SOS-dependent skin tumor development.</strong> Cell 102: 211-220, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10943841/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10943841</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)00026-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10943841">Sibilia et al. (2000)</a> found that transgenic mice expressing SOS-F (a dominant form of SOS1 lacking the C-terminal region containing the GRB2-binding site and instead carrying the c-Ha-ras farnesylation site, which provides constitutive activity) driven by the keratin-5 (K5, or KRT5; <a href="/entry/148040">148040</a>) promoter in basal keratinocytes developed skin papillomas with 100% penetrance. Tumor formation was inhibited, however, in mice with a hypomorphic (waved-2, or wa2, mice) and null Egfr background. Similarly, Egfr-deficient fibroblasts were resistant to transformation by SOS-F and rasV12, although tumorigenicity could be restored by expression of the antiapoptotic Bcl2 gene (<a href="/entry/151430">151430</a>). The K5-SOS-F papillomas and primary keratinocytes from wa2 mice displayed increased apoptosis and reduced Akt (<a href="/entry/164730">164730</a>) phosphorylation, and grafting experiments implied a cell-autonomous requirement for Egfr in keratinocytes. The authors concluded that EGFR provides an essential survival signal for SOS-dependent skin tumor development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10943841" 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="#6" class="mim-tip-reference" title="Huang, W. Y. C., Alvarez, S., Kondo, Y., Lee, Y. K., Chung, J. K., Lam, H. Y. M., Biswas, K. H., Kuriyan, J., Groves, J. T. <strong>A molecular assembly phase transition and kinetic proofreading modulate Ras activation by SOS.</strong> Science 363: 1098-1103, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30846600/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30846600</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30846600[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/10.1126/science.aau5721" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30846600">Huang et al. (2019)</a> observed a multistep activation process for SOS which they suggested could, in principle, lead to longer-dwelling molecules having disproportionately higher activation rates, and showed that SOS activity is capable of being modulated by a kinetic proofreading mechanism. SOS is a key RAS activator that is autoinhibited in the cytosol and activates upon membrane recruitment. Autoinhibition release involves structural rearrangements of the protein at the membrane and thus introduces a delay between initial recruitment and activation. <a href="#6" class="mim-tip-reference" title="Huang, W. Y. C., Alvarez, S., Kondo, Y., Lee, Y. K., Chung, J. K., Lam, H. Y. M., Biswas, K. H., Kuriyan, J., Groves, J. T. <strong>A molecular assembly phase transition and kinetic proofreading modulate Ras activation by SOS.</strong> Science 363: 1098-1103, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30846600/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30846600</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30846600[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/10.1126/science.aau5721" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30846600">Huang et al. (2019)</a> designed a single-molecule assay to resolve the time between initial receptor-mediated membrane recruitment and the initiation of GEF activity of individual SOS molecules on microarrays of RAS-functionalized supported membranes. The rise-and-fall shape of the measured SOS activation time distribution and the long mean time scale to activation (approximately 50 seconds) established a basis for kinetic proofreading in the receptor-mediated activation of RAS. <a href="#6" class="mim-tip-reference" title="Huang, W. Y. C., Alvarez, S., Kondo, Y., Lee, Y. K., Chung, J. K., Lam, H. Y. M., Biswas, K. H., Kuriyan, J., Groves, J. T. <strong>A molecular assembly phase transition and kinetic proofreading modulate Ras activation by SOS.</strong> Science 363: 1098-1103, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30846600/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30846600</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30846600[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/10.1126/science.aau5721" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30846600">Huang et al. (2019)</a> further demonstrated that this kinetic proofreading is modulated by the LAT (<a href="/entry/602354">602354</a>)-GRB2 (<a href="/entry/108355">108355</a>)-SOS phosphotyrosine-driven phase transition at the membrane. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30846600" 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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To identify the gene responsible for autosomal dominant gingival fibromatosis (GINGF1; <a href="/entry/135300">135300</a>) mapped to chromosome 2p21, <a href="#5" class="mim-tip-reference" title="Hart, T. C., Zhang, Y., Gorry, M. C., Hart, P. S., Cooper, M., Marazita, M. L., Marks, J. M., Cortelli, J. R., Pallos, D. <strong>A mutation in the SOS1 gene causes hereditary gingival fibromatosis type 1.</strong> Am. J. Hum. Genet. 70: 943-954, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11868160/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11868160</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11868160[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/10.1086/339689" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11868160">Hart et al. (2002)</a> extended genetic linkage studies to refine the candidate interval; 16 genes were identified. Sequencing of these genes identified a mutation (<a href="#0001">182530.0001</a>) in the SOS1 gene in affected individuals of a large multigenerational Brazilian family. A transgenic mouse construct with a comparable SOS1 mutation was found to produce a phenotype with skin hypertrophy (<a href="#11" class="mim-tip-reference" title="Sibilia, M., Fleischmann, A., Behrens, A., Stingl, L., Carroll, J., Watt, F. M., Schlessinger, J., Wagner, E. F. <strong>The EGF receptor provides an essential survival signal for SOS-dependent skin tumor development.</strong> Cell 102: 211-220, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10943841/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10943841</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)00026-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10943841">Sibilia et al., 2000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10943841+11868160" 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 affected individuals from a Brazilian family with severe gingival overgrowth, <a href="#7" class="mim-tip-reference" title="Machado, R. A., de Andrade, R. S., Pego, S. P. B., Krepischi, A. C. V., Coletta, R. D., Martelli-Junior, H. <strong>New evidence of genetic heterogeneity causing hereditary gingival fibromatosis and ALK and CD36 as new candidate genes.</strong> J. Periodont. 94: 108-118, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35665929/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35665929</a>] [<a href="https://doi.org/10.1002/JPER.22-0219" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="35665929">Machado et al. (2023)</a> identified heterozygosity for a 4-bp insertion in the SOS1 gene (<a href="#0008">182530.0008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35665929" 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><strong><em>Noonan Syndrome 4</em></strong></p><p>
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Noonan syndrome (see NS4; <a href="/entry/610733">610733</a>) is a developmental disorder characterized by short stature, facial dysmorphism, congenital heart defects, and skeletal anomalies. Gain-of-function mutations in PTPN11 (<a href="/entry/176876">176876</a>), which encodes the tyrosine phosphatase SHP2, cause approximately 50% of Noonan syndrome cases. Mutations in KRAS (<a href="/entry/190070">190070</a>) cause less than 5% of Noonan syndrome cases. Both SHP2 and KRAS participate in signaling through the RAS GTPase. <a href="#9" class="mim-tip-reference" title="Roberts, A. E., Araki, T., Swanson, K. D., Montgomery, K. T., Schiripo, T. A., Joshi, V. A., Li, L., Yassin, Y., Tamburino, A. M., Neel, B. G., Kucherlapati, R. S. <strong>Germline gain-of-function mutations in SOS1 cause Noonan syndrome.</strong> Nature Genet. 39: 70-74, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17143285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17143285</a>] [<a href="https://doi.org/10.1038/ng1926" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17143285">Roberts et al. (2007)</a> and <a href="#13" class="mim-tip-reference" title="Tartaglia, M., Pennacchio, L. A., Zhao, C., Yadav, K. K., Fodale, V., Sarkozy, A., Pandit, B., Oishi, K., Martinelli, S., Schackwitz, W., Ustaszewska, A., Martin, J., and 13 others. <strong>Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome.</strong> Nature Genet. 39: 75-79, 2007. Note: Erratum: Nature Genet. 39: 276 only, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17143282/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17143282</a>] [<a href="https://doi.org/10.1038/ng1939" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17143282">Tartaglia et al. (2007)</a> identified mutations in SOS1, which encodes an essential RAS guanine nucleotide exchange factor (GEF), in Noonan syndrome patients. Among patients with Noonan syndrome without mutation in PTPN11 or KRAS, <a href="#9" class="mim-tip-reference" title="Roberts, A. E., Araki, T., Swanson, K. D., Montgomery, K. T., Schiripo, T. A., Joshi, V. A., Li, L., Yassin, Y., Tamburino, A. M., Neel, B. G., Kucherlapati, R. S. <strong>Germline gain-of-function mutations in SOS1 cause Noonan syndrome.</strong> Nature Genet. 39: 70-74, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17143285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17143285</a>] [<a href="https://doi.org/10.1038/ng1926" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17143285">Roberts et al. (2007)</a> found missense SOS1 mutations in approximately 20%; <a href="#13" class="mim-tip-reference" title="Tartaglia, M., Pennacchio, L. A., Zhao, C., Yadav, K. K., Fodale, V., Sarkozy, A., Pandit, B., Oishi, K., Martinelli, S., Schackwitz, W., Ustaszewska, A., Martin, J., and 13 others. <strong>Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome.</strong> Nature Genet. 39: 75-79, 2007. Note: Erratum: Nature Genet. 39: 276 only, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17143282/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17143282</a>] [<a href="https://doi.org/10.1038/ng1939" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17143282">Tartaglia et al. (2007)</a>, in 22 of 129 such individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17143285+17143282" 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>Noonan syndrome shares some phenotypic features with cardiofaciocutaneous syndrome (CFCS; <a href="/entry/115150">115150</a>). Furthermore, both are due to heterozygous gain-of-function mutations in genes encoding proteins of the Ras-MAPK signaling cascade. <a href="#17" class="mim-tip-reference" title="Zenker, M., Horn, D., Wieczorek, D., Allanson, J., Pauli, S., van der Burgt, I., Doerr, H.-G., Gaspar, H., Hofbeck, M., Gillessen-Kaesbach, G., Koch, A., Meinecke, P., and 13 others. <strong>SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome. (Letter)</strong> J. Med. Genet. 44: 651-656, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17586837/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17586837</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17586837[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/10.1136/jmg.2007.051276" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17586837">Zenker et al. (2007)</a> investigated SOS1 in a large cohort of patients with disorders of the NS-CFCS spectrum, who had previously tested negative for mutations in PTPN11, KRAS, BRAF (<a href="/entry/164757">164757</a>), MEK1 (<a href="/entry/176872">176872</a>), and MEK2 (<a href="/entry/601263">601263</a>). Missense mutations of SOS1 were discovered in 28% of patients with Noonan syndrome, thus confirming SOS1 as the second major gene for that disorder. In contrast, none of the patients classified as having CFCS carried a pathogenic sequence change in the SOS1 gene. Patients with NS and mutations in SOS1 (NS4; <a href="/entry/610733">610733</a>) have a distinctive phenotype with frequent ectodermal anomalies such as keratosis pilaris and curly hair. Findings corroborated that, despite being caused by gain-of-function mutations in molecules belonging to the same pathway, NS and CFCS scarcely overlap genotypically. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17586837" 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 10 affected members of a 3-generation family segregating NS4, <a href="#14" class="mim-tip-reference" title="van Trier, D. C., Rinne, T., Noordam, K., Draaisma, J. M., van der Burgt, I. <strong>Variable phenotypic expression in a large Noonan syndrome family segregating a novel SOS1 mutation.</strong> Am. J. Med. Genet. 173A: 2968-2972, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28884940/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28884940</a>] [<a href="https://doi.org/10.1002/ajmg.a.38466" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28884940">van Trier et al. (2017)</a> identified a heterozygous missense mutation (P1045R; <a href="#0007">182530.0007</a>) in the SOS1 gene. The mutation was identified in the proband (patient IV-8) by next-generation sequencing of an NS gene panel and in additional family members by Sanger sequencing. No other pathogenic mutations or variants of uncertain significance were identified, and the mutation segregated with the disorder in the family. There was a range of clinical expression among the 10 family members from almost no NS4 characteristics to a typical presentation. The family was part of an NS cohort previously studied by <a href="#15" class="mim-tip-reference" title="van Trier, D. C., van Nierop, J., Draaisma, J. M., van der Burgt, I., Kunst, H., Croonen, E. A., Admiraal, R. J. C. <strong>External ear anomalies and hearing impairment in Noonan syndrome.</strong> Int. J. Pediat. Otorhinolaryng. 79: 874-878, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25862627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25862627</a>] [<a href="https://doi.org/10.1016/j.ijporl.2015.03.021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25862627">van Trier et al. (2015)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=25862627+28884940" 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 an extensive Brazilian family with hereditary gingival fibromatosis (GINGF1; <a href="/entry/135300">135300</a>), <a href="#5" class="mim-tip-reference" title="Hart, T. C., Zhang, Y., Gorry, M. C., Hart, P. S., Cooper, M., Marazita, M. L., Marks, J. M., Cortelli, J. R., Pallos, D. <strong>A mutation in the SOS1 gene causes hereditary gingival fibromatosis type 1.</strong> Am. J. Hum. Genet. 70: 943-954, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11868160/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11868160</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11868160[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/10.1086/339689" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11868160">Hart et al. (2002)</a> demonstrated that the disorder was caused by insertion of a cytosine between nucleotides 126142 and 126143 in codon 1083 of the SOS1 gene. The insertion mutation introduced a frameshift and created a premature stop codon, abolishing 4 functionally important proline-rich SH3 binding domains normally present in the carboxyl-terminal region of the SOS1 protein. In the cDNA sequence, the insertion was between nucleotides 3248 and 3249. The mutation yielded a chimeric 1,105-amino acid protein that consisted of 1,083 SOS1 N-terminal amino acids in a normal sequence, followed by 22 replaced amino acids and a premature stop codon at codon 1106. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11868160" 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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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000013729 OR RCV000038570 OR RCV000149833 OR RCV000213007 OR RCV000515403 OR RCV003450637" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013729, RCV000038570, RCV000149833, RCV000213007, RCV000515403, RCV003450637" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013729...</a>
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<p>In a 6-year-old girl with sporadic Noonan syndrome (NS4; <a href="/entry/610733">610733</a>), <a href="#9" class="mim-tip-reference" title="Roberts, A. E., Araki, T., Swanson, K. D., Montgomery, K. T., Schiripo, T. A., Joshi, V. A., Li, L., Yassin, Y., Tamburino, A. M., Neel, B. G., Kucherlapati, R. S. <strong>Germline gain-of-function mutations in SOS1 cause Noonan syndrome.</strong> Nature Genet. 39: 70-74, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17143285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17143285</a>] [<a href="https://doi.org/10.1038/ng1926" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17143285">Roberts et al. (2007)</a> found a 797C-A transversion in exon 6 of the SOS1 gene that resulted in a thr266-to-lys substitution (T266K). The child had hypertrophic cardiomyopathy with thrombocytopenia and easy bruising. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17143285" 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="#3" class="mim-tip-reference" title="Ferrero, G. B., Baldassarre, G., Delmonaco, A. G., Biamino, E., Banaudi, E., Carta, C., Rossi, C., Silengo, M. C. <strong>Clinical and molecular characterization of 40 patients with Noonan syndrome.</strong> Europ. J. Med. Genet. 51: 566-572, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18678287/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18678287</a>] [<a href="https://doi.org/10.1016/j.ejmg.2008.06.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18678287">Ferrero et al. (2008)</a> reported a newborn with Noonan syndrome and the T266K mutation. The pregnancy was characterized by polyhydramnios and increased fetal nuchal translucency. Dysmorphic facial features included hypertelorism, epicanthal folds, flat nasal bridge, low-set posteriorly rotated ears, and short neck. Other features included moderate pulmonic stenosis and bilateral cryptorchidism. Developmental milestones were normal at 24 months of age. There were no coagulation abnormalities. <a href="#3" class="mim-tip-reference" title="Ferrero, G. B., Baldassarre, G., Delmonaco, A. G., Biamino, E., Banaudi, E., Carta, C., Rossi, C., Silengo, M. C. <strong>Clinical and molecular characterization of 40 patients with Noonan syndrome.</strong> Europ. J. Med. Genet. 51: 566-572, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18678287/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18678287</a>] [<a href="https://doi.org/10.1016/j.ejmg.2008.06.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18678287">Ferrero et al. (2008)</a> noted the phenotypic differences from the patient reported by <a href="#9" class="mim-tip-reference" title="Roberts, A. E., Araki, T., Swanson, K. D., Montgomery, K. T., Schiripo, T. A., Joshi, V. A., Li, L., Yassin, Y., Tamburino, A. M., Neel, B. G., Kucherlapati, R. S. <strong>Germline gain-of-function mutations in SOS1 cause Noonan syndrome.</strong> Nature Genet. 39: 70-74, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17143285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17143285</a>] [<a href="https://doi.org/10.1038/ng1926" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17143285">Roberts et al. (2007)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17143285+18678287" 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">rs137852813 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852813;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=rs137852813" 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=rs137852813" 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=RCV000013730 OR RCV000157691 OR RCV000211854 OR RCV000554031 OR RCV000856805 OR RCV002415412" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013730, RCV000157691, RCV000211854, RCV000554031, RCV000856805, RCV002415412" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013730...</a>
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<p>In 2 patients with sporadic Noonan syndrome (NS4; <a href="/entry/610733">610733</a>), <a href="#9" class="mim-tip-reference" title="Roberts, A. E., Araki, T., Swanson, K. D., Montgomery, K. T., Schiripo, T. A., Joshi, V. A., Li, L., Yassin, Y., Tamburino, A. M., Neel, B. G., Kucherlapati, R. S. <strong>Germline gain-of-function mutations in SOS1 cause Noonan syndrome.</strong> Nature Genet. 39: 70-74, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17143285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17143285</a>] [<a href="https://doi.org/10.1038/ng1926" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17143285">Roberts et al. (2007)</a> detected an 806T-G transversion in the SOS1 gene that caused a met269-to-arg (M269R) substitution. One of the patients was a 7-year-old boy with pulmonic stenosis and hypertrophic cardiomyopathy, easy bruising, and cryptorchidism with inguinal hernia. The other was an 11-year-old boy with pulmonic stenosis and atrial septal defect and cryptorchidism. School placement was regular in both cases. <a href="#13" class="mim-tip-reference" title="Tartaglia, M., Pennacchio, L. A., Zhao, C., Yadav, K. K., Fodale, V., Sarkozy, A., Pandit, B., Oishi, K., Martinelli, S., Schackwitz, W., Ustaszewska, A., Martin, J., and 13 others. <strong>Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome.</strong> Nature Genet. 39: 75-79, 2007. Note: Erratum: Nature Genet. 39: 276 only, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17143282/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17143282</a>] [<a href="https://doi.org/10.1038/ng1939" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17143282">Tartaglia et al. (2007)</a> identified the same mutation in 1 patient, also a sporadic case. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17143285+17143282" 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"><span class="text-primary">●</span> rs137852814 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852814;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852814?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852814" 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=rs137852814" 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=RCV000013731 OR RCV000156980 OR RCV000157693 OR RCV000159174 OR RCV000515160 OR RCV002399321" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013731, RCV000156980, RCV000157693, RCV000159174, RCV000515160, RCV002399321" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013731...</a>
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<p>In a 41-year-old father and his infant son, <a href="#9" class="mim-tip-reference" title="Roberts, A. E., Araki, T., Swanson, K. D., Montgomery, K. T., Schiripo, T. A., Joshi, V. A., Li, L., Yassin, Y., Tamburino, A. M., Neel, B. G., Kucherlapati, R. S. <strong>Germline gain-of-function mutations in SOS1 cause Noonan syndrome.</strong> Nature Genet. 39: 70-74, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17143285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17143285</a>] [<a href="https://doi.org/10.1038/ng1926" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17143285">Roberts et al. (2007)</a> found that Noonan syndrome (NS4; <a href="/entry/610733">610733</a>) was associated with a missense mutation in the SOS1 gene: an arg552-to-gly substitution (R552G) caused by a 1654A-G transition. The son had pulmonic stenosis. The father had cryptorchidism. Both showed 25 to 50% normal linear growth. <a href="#13" class="mim-tip-reference" title="Tartaglia, M., Pennacchio, L. A., Zhao, C., Yadav, K. K., Fodale, V., Sarkozy, A., Pandit, B., Oishi, K., Martinelli, S., Schackwitz, W., Ustaszewska, A., Martin, J., and 13 others. <strong>Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome.</strong> Nature Genet. 39: 75-79, 2007. Note: Erratum: Nature Genet. 39: 276 only, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17143282/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17143282</a>] [<a href="https://doi.org/10.1038/ng1939" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17143282">Tartaglia et al. (2007)</a> identified this mutation in 2 de novo cases. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17143285+17143282" 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">rs267607079 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267607079;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=rs267607079" 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=rs267607079" 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=RCV000013732 OR RCV000038525 OR RCV000149832 OR RCV000156992 OR RCV000159177 OR RCV000213008 OR RCV000515298 OR RCV000654947 OR RCV000763086 OR RCV000787997 OR RCV000787998 OR RCV000856746 OR RCV002250500 OR RCV002399362 OR RCV003128391" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013732, RCV000038525, RCV000149832, RCV000156992, RCV000159177, RCV000213008, RCV000515298, RCV000654947, RCV000763086, RCV000787997, RCV000787998, RCV000856746, RCV002250500, RCV002399362, RCV003128391" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013732...</a>
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<p>In a girl with Noonan syndrome-4 (NS4; <a href="/entry/610733">610733</a>) who had pigmented villonodular synovitis (PVNS), <a href="#8" class="mim-tip-reference" title="Mascheroni, E., Digilio, M. C., Cortis, E., Devito, R., Sarkozy, A., Capolino, R., Dallapiccola, B., Ugazio, A. G. <strong>Pigmented villonodular synovitis in a patient with Noonan syndrome and SOS1 gene mutation. (Letter)</strong> Am. J. Med. Genet. 146A: 2966-2967, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18925667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18925667</a>] [<a href="https://doi.org/10.1002/ajmg.a.32538" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18925667">Mascheroni et al. (2008)</a> identified a de novo heterozygous mutation in the SOS1 gene, resulting in an arg552-to-ser (R522S) substitution. She presented at 13 years with swelling and severe pain in her right foot and ankle. History and physical examination showed that she had multiple features of Noonan syndrome. <a href="#8" class="mim-tip-reference" title="Mascheroni, E., Digilio, M. C., Cortis, E., Devito, R., Sarkozy, A., Capolino, R., Dallapiccola, B., Ugazio, A. G. <strong>Pigmented villonodular synovitis in a patient with Noonan syndrome and SOS1 gene mutation. (Letter)</strong> Am. J. Med. Genet. 146A: 2966-2967, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18925667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18925667</a>] [<a href="https://doi.org/10.1002/ajmg.a.32538" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18925667">Mascheroni et al. (2008)</a> suggested that PVNS is a proliferative lesion that is part of the phenotypic spectrum of Noonan syndrome. Another mutation in this same codon (R552G; <a href="#0004">182530.0004</a>) has also been reported. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18925667" 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">rs267607080 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267607080;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=rs267607080" 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=rs267607080" 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=RCV000013733 OR RCV000159161 OR RCV000211853 OR RCV000818949" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013733, RCV000159161, RCV000211853, RCV000818949" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013733...</a>
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<p>In 2 brothers, born of consanguineous parents, with Noonan syndrome-4 (NS4; <a href="/entry/610733">610733</a>) and multiple giant cell lesions, <a href="#4" class="mim-tip-reference" title="Hanna, N., Parfait, B., Talaat, I. M., Vidaud, M., Elsedfy, H. H. <strong>SOS1: a new player in the Noonan-like/multiple giant cell lesion syndrome.</strong> Clin. Genet. 75: 568-571, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19438935/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19438935</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2009.01149.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19438935">Hanna et al. (2009)</a> identified a heterozygous 1294T-C transition in exon 10 of the SOS1 gene, resulting in a trp432-to-arg (W432R) substitution within the pleckstrin homology domain. One boy presented at age 4.5 years with a 2-year history of bilateral progressive swelling of the mandible. Radiographic studies showed multilocular lesions of the mandibular rami, consistent with giant cell lesions. The boy's 6.5-year-old brother presented with severe pulmonary valvular stenosis and was found to have similar multilocular lesions of the mandible as his brother. Both boys had characteristic facial features of Noonan syndrome, including high anterior hairline with frontal bossing, follicular hyperkeratosis of the forehead (keratosis pilaris), depressed nasal bridge, hypertelorism, downslanting palpebral fissures, and low-set and posteriorly angulated ears with thick helices. Other features included short neck and widely spaced nipples. Both showed normal development and normal stature. The father showed milder features of the disorder, with long face, downslanting palpebral fissures, low-set ears, and widely spaced nipples, and was also heterozygous for the W432R mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19438935" 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 NOONAN SYNDROME 4</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">rs1668859370 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1668859370;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=rs1668859370" 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=rs1668859370" 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=RCV001200895" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001200895" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001200895</a>
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<p>In 10 affected members of a 3-generation family segregating Noonan syndrome-4 (NS4; <a href="/entry/610733">610733</a>), <a href="#14" class="mim-tip-reference" title="van Trier, D. C., Rinne, T., Noordam, K., Draaisma, J. M., van der Burgt, I. <strong>Variable phenotypic expression in a large Noonan syndrome family segregating a novel SOS1 mutation.</strong> Am. J. Med. Genet. 173A: 2968-2972, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28884940/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28884940</a>] [<a href="https://doi.org/10.1002/ajmg.a.38466" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28884940">van Trier et al. (2017)</a> identified a heterozygous c.3134C-G transversion (c.3134C-G, NM_005633.3) in the SOS1 gene, resulting in a pro1045-to-arg (P1045R) substitution at a moderately conserved residue. The mutation was identified in the proband (patient IV-8) by next-generation sequencing of an NS gene panel and in additional family members by Sanger sequencing. No other pathogenic mutations or variants of uncertain significance were identified, and the mutation segregated with the disorder in the family. There was a range of clinical expression among the 10 family members from almost no NS4 characteristics to a typical presentation. The family was part of an NS cohort previously studied by <a href="#15" class="mim-tip-reference" title="van Trier, D. C., van Nierop, J., Draaisma, J. M., van der Burgt, I., Kunst, H., Croonen, E. A., Admiraal, R. J. C. <strong>External ear anomalies and hearing impairment in Noonan syndrome.</strong> Int. J. Pediat. Otorhinolaryng. 79: 874-878, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25862627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25862627</a>] [<a href="https://doi.org/10.1016/j.ijporl.2015.03.021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25862627">van Trier et al. (2015)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=25862627+28884940" 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 FIBROMATOSIS, GINGIVAL, 1</strong>
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SOS1, 4-BP INS, 3265TAAC
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV004776463" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV004776463" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV004776463</a>
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<p>In a 14-year-old girl, her mother, and a maternal aunt (family D) with severe gingival overgrowth (GINGF1; <a href="/entry/135300">135300</a>), <a href="#7" class="mim-tip-reference" title="Machado, R. A., de Andrade, R. S., Pego, S. P. B., Krepischi, A. C. V., Coletta, R. D., Martelli-Junior, H. <strong>New evidence of genetic heterogeneity causing hereditary gingival fibromatosis and ALK and CD36 as new candidate genes.</strong> J. Periodont. 94: 108-118, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35665929/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35665929</a>] [<a href="https://doi.org/10.1002/JPER.22-0219" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="35665929">Machado et al. (2023)</a> identified heterozygosity for a 4-bp insertion (c.3265_3266insTAAC) in the SOS1 gene, causing a frameshift predicted to result in a premature termination codon (Pro1089LeufsTer). DNA was unavailable from unaffected family members for segregation analysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35665929" 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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<a id="1" class="mim-anchor"></a>
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<a id="Bowtell1992" class="mim-anchor"></a>
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Bowtell, D., Fu, P., Simon, M. A., Senior, P.
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<strong>Identification of murine homologues of the Drosophila Son of sevenless gene: potential activators of ras.</strong>
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Proc. Nat. Acad. Sci. 89: 6511-6515, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1631150/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1631150</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1631150" 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.89.14.6511" target="_blank">Full Text</a>]
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Chardin, P., Camonis, J. H., Gale, N. W., Van Aelst, L., Schlessinger, J., Wigler, M. H., Bar-Sagi, D.
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<strong>Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2.</strong>
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Science 260: 1338-1343, 1993.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8493579/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8493579</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8493579" 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/10.1126/science.8493579" target="_blank">Full Text</a>]
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Ferrero, G. B., Baldassarre, G., Delmonaco, A. G., Biamino, E., Banaudi, E., Carta, C., Rossi, C., Silengo, M. C.
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<strong>Clinical and molecular characterization of 40 patients with Noonan syndrome.</strong>
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Europ. J. Med. Genet. 51: 566-572, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18678287/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18678287</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18678287" 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.ejmg.2008.06.011" target="_blank">Full Text</a>]
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Hanna, N., Parfait, B., Talaat, I. M., Vidaud, M., Elsedfy, H. H.
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<strong>SOS1: a new player in the Noonan-like/multiple giant cell lesion syndrome.</strong>
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Clin. Genet. 75: 568-571, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19438935/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19438935</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19438935" 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/10.1111/j.1399-0004.2009.01149.x" target="_blank">Full Text</a>]
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Hart, T. C., Zhang, Y., Gorry, M. C., Hart, P. S., Cooper, M., Marazita, M. L., Marks, J. M., Cortelli, J. R., Pallos, D.
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<strong>A mutation in the SOS1 gene causes hereditary gingival fibromatosis type 1.</strong>
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Am. J. Hum. Genet. 70: 943-954, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11868160/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11868160</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11868160[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=11868160" 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/10.1086/339689" target="_blank">Full Text</a>]
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Huang, W. Y. C., Alvarez, S., Kondo, Y., Lee, Y. K., Chung, J. K., Lam, H. Y. M., Biswas, K. H., Kuriyan, J., Groves, J. T.
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<strong>A molecular assembly phase transition and kinetic proofreading modulate Ras activation by SOS.</strong>
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Science 363: 1098-1103, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30846600/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30846600</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30846600[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=30846600" 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/10.1126/science.aau5721" target="_blank">Full Text</a>]
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<a id="Machado2023" class="mim-anchor"></a>
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Machado, R. A., de Andrade, R. S., Pego, S. P. B., Krepischi, A. C. V., Coletta, R. D., Martelli-Junior, H.
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<strong>New evidence of genetic heterogeneity causing hereditary gingival fibromatosis and ALK and CD36 as new candidate genes.</strong>
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J. Periodont. 94: 108-118, 2023.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35665929/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35665929</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35665929" 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/JPER.22-0219" target="_blank">Full Text</a>]
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Mascheroni, E., Digilio, M. C., Cortis, E., Devito, R., Sarkozy, A., Capolino, R., Dallapiccola, B., Ugazio, A. G.
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<strong>Pigmented villonodular synovitis in a patient with Noonan syndrome and SOS1 gene mutation. (Letter)</strong>
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Am. J. Med. Genet. 146A: 2966-2967, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18925667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18925667</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18925667" 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/ajmg.a.32538" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="9" class="mim-anchor"></a>
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<a id="Roberts2007" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Roberts, A. E., Araki, T., Swanson, K. D., Montgomery, K. T., Schiripo, T. A., Joshi, V. A., Li, L., Yassin, Y., Tamburino, A. M., Neel, B. G., Kucherlapati, R. S.
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<strong>Germline gain-of-function mutations in SOS1 cause Noonan syndrome.</strong>
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Nature Genet. 39: 70-74, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17143285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17143285</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17143285" 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/ng1926" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="10" class="mim-anchor"></a>
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<a id="Scita1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Scita, G., Nordstrom, J., Carbone, R., Tenca, P., Giardina, G., Gutkind, S., Bjarnegard, M., Betsholtz, C., Di Fiore, P. P.
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<strong>EPS8 and E3B1 transduce signals from Ras to Rac.</strong>
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Nature 401: 290-293, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10499589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10499589</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10499589" 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/10.1038/45822" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="11" class="mim-anchor"></a>
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<a id="Sibilia2000" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Sibilia, M., Fleischmann, A., Behrens, A., Stingl, L., Carroll, J., Watt, F. M., Schlessinger, J., Wagner, E. F.
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<strong>The EGF receptor provides an essential survival signal for SOS-dependent skin tumor development.</strong>
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Cell 102: 211-220, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10943841/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10943841</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10943841" 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/s0092-8674(00)00026-x" target="_blank">Full Text</a>]
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<li>
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<a id="12" class="mim-anchor"></a>
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<a id="Soisson1998" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Soisson, S. M., Nimnual, A. S., Uy, M., Bar-Sagi, D., Kuriyan, J.
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<strong>Crystal structure of the Dbl and pleckstrin homology domains from the human Son of sevenless protein.</strong>
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Cell 95: 259-268, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9790532/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9790532</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9790532" 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/s0092-8674(00)81756-0" target="_blank">Full Text</a>]
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<a id="13" class="mim-anchor"></a>
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<a id="Tartaglia2007" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tartaglia, M., Pennacchio, L. A., Zhao, C., Yadav, K. K., Fodale, V., Sarkozy, A., Pandit, B., Oishi, K., Martinelli, S., Schackwitz, W., Ustaszewska, A., Martin, J., and 13 others.
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<strong>Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome.</strong>
|
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Nature Genet. 39: 75-79, 2007. Note: Erratum: Nature Genet. 39: 276 only, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17143282/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17143282</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17143282" 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/ng1939" target="_blank">Full Text</a>]
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<li>
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<a id="14" class="mim-anchor"></a>
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<a id="van Trier2017" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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van Trier, D. C., Rinne, T., Noordam, K., Draaisma, J. M., van der Burgt, I.
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<strong>Variable phenotypic expression in a large Noonan syndrome family segregating a novel SOS1 mutation.</strong>
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Am. J. Med. Genet. 173A: 2968-2972, 2017.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28884940/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28884940</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28884940" 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/ajmg.a.38466" target="_blank">Full Text</a>]
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<li>
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<a id="15" class="mim-anchor"></a>
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<a id="van Trier2015" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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van Trier, D. C., van Nierop, J., Draaisma, J. M., van der Burgt, I., Kunst, H., Croonen, E. A., Admiraal, R. J. C.
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<strong>External ear anomalies and hearing impairment in Noonan syndrome.</strong>
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Int. J. Pediat. Otorhinolaryng. 79: 874-878, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25862627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25862627</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25862627" 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.ijporl.2015.03.021" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="16" class="mim-anchor"></a>
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<a id="Webb1993" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Webb, G. C., Jenkins, N. A., Largaespada, D. A., Copeland, N. G., Fernandez, C. S., Bowtell, D. D. L.
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<strong>Mammalian homologues of the Drosophila Son of sevenless gene map to murine chromosomes 17 and 12 and to human chromosomes 2 and 14, respectively.</strong>
|
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Genomics 18: 14-19, 1993.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8276400/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8276400</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8276400" 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/10.1006/geno.1993.1421" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="17" class="mim-anchor"></a>
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<a id="Zenker2007" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zenker, M., Horn, D., Wieczorek, D., Allanson, J., Pauli, S., van der Burgt, I., Doerr, H.-G., Gaspar, H., Hofbeck, M., Gillessen-Kaesbach, G., Koch, A., Meinecke, P., and 13 others.
|
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<strong>SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome. (Letter)</strong>
|
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J. Med. Genet. 44: 651-656, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17586837/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17586837</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17586837[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=17586837" 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/10.1136/jmg.2007.051276" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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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>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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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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Marla J. F. O'Neill - updated : 10/31/2024
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 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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Hilary J. Vernon - updated : 07/07/2020<br>Ada Hamosh - updated : 10/01/2019<br>Cassandra L. Kniffin - updated : 6/1/2010<br>Cassandra L. Kniffin - updated : 6/18/2009<br>Cassandra L. Kniffin - updated : 3/3/2009<br>Victor A. McKusick - updated : 12/28/2007<br>Victor A. McKusick - updated : 1/30/2007<br>Victor A. McKusick - updated : 4/12/2002<br>Stylianos E. Antonarakis - updated : 8/8/2000<br>Ada Hamosh - updated : 2/14/2000<br>Stylianos E. Antonarakis - updated : 11/6/1998<br>Alan F. Scott - updated : 5/5/1996
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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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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Victor A. McKusick : 6/22/1993
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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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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alopez : 10/31/2024
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 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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carol : 07/07/2020<br>alopez : 10/01/2019<br>carol : 08/22/2019<br>carol : 10/01/2015<br>carol : 9/23/2015<br>terry : 4/9/2012<br>carol : 9/29/2011<br>wwang : 11/5/2010<br>ckniffin : 10/26/2010<br>wwang : 10/6/2010<br>wwang : 6/4/2010<br>ckniffin : 6/1/2010<br>wwang : 7/21/2009<br>ckniffin : 6/18/2009<br>wwang : 3/10/2009<br>ckniffin : 3/3/2009<br>alopez : 8/20/2008<br>alopez : 1/25/2008<br>terry : 12/28/2007<br>terry : 8/6/2007<br>alopez : 2/19/2007<br>alopez : 1/31/2007<br>terry : 1/30/2007<br>alopez : 4/25/2002<br>alopez : 4/25/2002<br>cwells : 4/19/2002<br>terry : 4/12/2002<br>alopez : 1/9/2002<br>mgross : 8/8/2000<br>mgross : 8/8/2000<br>alopez : 3/3/2000<br>alopez : 2/14/2000<br>carol : 9/20/1999<br>psherman : 11/13/1998<br>psherman : 11/6/1998<br>alopez : 7/13/1998<br>terry : 5/7/1996<br>mark : 5/7/1996<br>mark : 5/5/1996<br>mark : 5/5/1996<br>carol : 11/8/1994<br>carol : 6/22/1993
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</span>
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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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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 182530
|
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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SOS RAS/RAC GUANINE NUCLEOTIDE EXCHANGE FACTOR 1; SOS1
|
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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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<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>
|
|
<span class="mim-font">
|
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SON OF SEVENLESS, DROSOPHILA, HOMOLOG 1<br />
|
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SOS1 GUANINE NUCLEOTIDE EXCHANGE FACTOR
|
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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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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: SOS1</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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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 2p22.1
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Genomic coordinates <span class="small">(GRCh38)</span> : 2:38,981,549-39,124,868 </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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</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>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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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>
|
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Inheritance
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</th>
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<th>
|
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Phenotype <br /> mapping key
|
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</th>
|
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</tr>
|
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</thead>
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<tbody>
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<tr>
|
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<td rowspan="2">
|
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<span class="mim-font">
|
|
2p22.1
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</span>
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</td>
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<td>
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<span class="mim-font">
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|
Fibromatosis, gingival, 1
|
|
</span>
|
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</td>
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<td>
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<span class="mim-font">
|
|
135300
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</span>
|
|
</td>
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<td>
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<span class="mim-font">
|
|
Autosomal dominant
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|
</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
3
|
|
</span>
|
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</td>
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</tr>
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<tr>
|
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<td>
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<span class="mim-font">
|
|
Noonan syndrome 4
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|
</span>
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</td>
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<td>
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<span class="mim-font">
|
|
610733
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|
</span>
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</td>
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<td>
|
|
<span class="mim-font">
|
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Autosomal dominant
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
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</td>
|
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</tr>
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|
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|
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</tbody>
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</table>
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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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<h4>
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<span class="mim-font">
|
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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|
<p>RAS genes (e.g., 190020) encode membrane-bound guanine nucleotide-binding proteins that function in the transduction of signals that control cell growth and differentiation. Binding of GTP activates RAS proteins, and subsequent hydrolysis of the bound GTP to GDP and phosphate inactivates signaling by these proteins. GTP binding can be catalyzed by guanine nucleotide exchange factors for RAS, and GTP hydrolysis can be accelerated by GTPase-activating proteins (GAPs). The first exchange factor to be identified for RAS was the S. cerevisiae CDC25 gene product. Genetic analysis indicated that CDC25 is essential for activation of RAS proteins. In Drosophila, the protein encoded by the 'son of sevenless' gene (Sos) contains a domain that shows sequence similarity with the catalytic domain of CDC25. Sos may act as a positive regulator of RAS by promoting guanine nucleotide exchange.</p>
|
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</span>
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<div>
|
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
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</div>
|
|
|
|
|
|
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<span class="mim-text-font">
|
|
<p>Bowtell et al. (1992) isolated 2 cDNAs, designated Sos1 and Sos2 (601247), from a mouse eye library by screening with a probe from the Drosophila Sos gene. Sos1 encodes a predicted 1,336-amino acid protein which is 67% identical to the partial Sos2 sequence. Both Sos1 and Sos2 have an overall amino acid identity of 45% with the Drosophila Sos gene product. Northern blots showed that both genes are expressed in a wide variety of tissues and cell lines. </p><p>Chardin et al. (1993) isolated a human cDNA that encodes a widely expressed 1,333-amino acid protein that is closely related to the product of the Drosophila Sos gene and nearly identical to the mouse Sos1 gene product. A fragment of the human gene encoding the CDC25-related domain complemented loss of CDC25 function in yeast. The same domain of the human gene specifically stimulated guanine nucleotide exchange on mammalian RAS proteins in vitro. This and other evidence indicated to Chardin et al. (1993) that SOS1 is a guanine nucleotide exchange factor for RAS in the human. Further studies suggested that the coupling of receptor tyrosine kinases to RAS signaling is mediated by a molecular complex consisting of growth factor receptor-bound protein-2 (108355) and SOS1. </p>
|
|
</span>
|
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<div>
|
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<br />
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</div>
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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<span class="mim-text-font">
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|
<p>Hart et al. (2002) determined that the SOS1 gene spans 136 kb and consists of 24 exons. Intronic sizes range from 30 bp to 53 kb. The translation initiation codon is located at nucleotides 45 to 47 of exon 2, and the open reading frame is terminated at nucleotide 492 in exon 24. </p>
|
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
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</h4>
|
|
</div>
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<span class="mim-text-font">
|
|
<p>Webb et al. (1993) mapped the mouse Sos1 gene to chromosome 17E by interspecific backcross analysis and in situ hybridization. They mapped the human SOS1 gene to chromosome 2p22-p21 by in situ hybridization. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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|
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Biochemical Features</strong>
|
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</span>
|
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</h4>
|
|
</div>
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|
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|
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<span class="mim-text-font">
|
|
<p><strong><em>Crystal Structure</em></strong></p><p>
|
|
Proteins containing Dbl homology (DH) domains, such as SOS1, activate Rho family GTPases by functioning as specific guanine nucleotide exchange factors. All known DH domains have associated C-terminal pleckstrin homology (PH) domains that are implicated in targeting and regulatory functions. Soisson et al. (1998) determined the crystal structure of a fragment of the human SOS1 protein containing the DH and PH domains at 2.3-angstrom resolution. The entirely alpha-helical DH domain was unrelated in architecture to other nucleotide exchange factors. The active site of the DH domain, identified on the basis of sequence conservation and structural features, lies near the interface between the DH and PH domains. The structure suggested to the authors that ligation of the PH domain will be coupled structurally to the GTPase-binding site. </p>
|
|
</span>
|
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<div>
|
|
<br />
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|
</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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|
|
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|
<span class="mim-text-font">
|
|
<p>Scita et al. (1999) showed that EPS8 (600206), E3B1 (603050), and SOS1 form a tricomplex in vivo that exhibits RAC (see 602048)-specific guanine nucleotide exchange factor (GEF) activity in vitro. </p><p>Epidermal growth factor receptor (EGFR; 131550) is required for skin development and is implicated in epithelial tumor formation. Sibilia et al. (2000) found that transgenic mice expressing SOS-F (a dominant form of SOS1 lacking the C-terminal region containing the GRB2-binding site and instead carrying the c-Ha-ras farnesylation site, which provides constitutive activity) driven by the keratin-5 (K5, or KRT5; 148040) promoter in basal keratinocytes developed skin papillomas with 100% penetrance. Tumor formation was inhibited, however, in mice with a hypomorphic (waved-2, or wa2, mice) and null Egfr background. Similarly, Egfr-deficient fibroblasts were resistant to transformation by SOS-F and rasV12, although tumorigenicity could be restored by expression of the antiapoptotic Bcl2 gene (151430). The K5-SOS-F papillomas and primary keratinocytes from wa2 mice displayed increased apoptosis and reduced Akt (164730) phosphorylation, and grafting experiments implied a cell-autonomous requirement for Egfr in keratinocytes. The authors concluded that EGFR provides an essential survival signal for SOS-dependent skin tumor development. </p><p>Huang et al. (2019) observed a multistep activation process for SOS which they suggested could, in principle, lead to longer-dwelling molecules having disproportionately higher activation rates, and showed that SOS activity is capable of being modulated by a kinetic proofreading mechanism. SOS is a key RAS activator that is autoinhibited in the cytosol and activates upon membrane recruitment. Autoinhibition release involves structural rearrangements of the protein at the membrane and thus introduces a delay between initial recruitment and activation. Huang et al. (2019) designed a single-molecule assay to resolve the time between initial receptor-mediated membrane recruitment and the initiation of GEF activity of individual SOS molecules on microarrays of RAS-functionalized supported membranes. The rise-and-fall shape of the measured SOS activation time distribution and the long mean time scale to activation (approximately 50 seconds) established a basis for kinetic proofreading in the receptor-mediated activation of RAS. Huang et al. (2019) further demonstrated that this kinetic proofreading is modulated by the LAT (602354)-GRB2 (108355)-SOS phosphotyrosine-driven phase transition at the membrane. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Gingival Fibromatosis 1</em></strong></p><p>
|
|
To identify the gene responsible for autosomal dominant gingival fibromatosis (GINGF1; 135300) mapped to chromosome 2p21, Hart et al. (2002) extended genetic linkage studies to refine the candidate interval; 16 genes were identified. Sequencing of these genes identified a mutation (182530.0001) in the SOS1 gene in affected individuals of a large multigenerational Brazilian family. A transgenic mouse construct with a comparable SOS1 mutation was found to produce a phenotype with skin hypertrophy (Sibilia et al., 2000). </p><p>In 3 affected individuals from a Brazilian family with severe gingival overgrowth, Machado et al. (2023) identified heterozygosity for a 4-bp insertion in the SOS1 gene (182530.0008). </p><p><strong><em>Noonan Syndrome 4</em></strong></p><p>
|
|
Noonan syndrome (see NS4; 610733) is a developmental disorder characterized by short stature, facial dysmorphism, congenital heart defects, and skeletal anomalies. Gain-of-function mutations in PTPN11 (176876), which encodes the tyrosine phosphatase SHP2, cause approximately 50% of Noonan syndrome cases. Mutations in KRAS (190070) cause less than 5% of Noonan syndrome cases. Both SHP2 and KRAS participate in signaling through the RAS GTPase. Roberts et al. (2007) and Tartaglia et al. (2007) identified mutations in SOS1, which encodes an essential RAS guanine nucleotide exchange factor (GEF), in Noonan syndrome patients. Among patients with Noonan syndrome without mutation in PTPN11 or KRAS, Roberts et al. (2007) found missense SOS1 mutations in approximately 20%; Tartaglia et al. (2007), in 22 of 129 such individuals. </p><p>Noonan syndrome shares some phenotypic features with cardiofaciocutaneous syndrome (CFCS; 115150). Furthermore, both are due to heterozygous gain-of-function mutations in genes encoding proteins of the Ras-MAPK signaling cascade. Zenker et al. (2007) investigated SOS1 in a large cohort of patients with disorders of the NS-CFCS spectrum, who had previously tested negative for mutations in PTPN11, KRAS, BRAF (164757), MEK1 (176872), and MEK2 (601263). Missense mutations of SOS1 were discovered in 28% of patients with Noonan syndrome, thus confirming SOS1 as the second major gene for that disorder. In contrast, none of the patients classified as having CFCS carried a pathogenic sequence change in the SOS1 gene. Patients with NS and mutations in SOS1 (NS4; 610733) have a distinctive phenotype with frequent ectodermal anomalies such as keratosis pilaris and curly hair. Findings corroborated that, despite being caused by gain-of-function mutations in molecules belonging to the same pathway, NS and CFCS scarcely overlap genotypically. </p><p>In 10 affected members of a 3-generation family segregating NS4, van Trier et al. (2017) identified a heterozygous missense mutation (P1045R; 182530.0007) in the SOS1 gene. The mutation was identified in the proband (patient IV-8) by next-generation sequencing of an NS gene panel and in additional family members by Sanger sequencing. No other pathogenic mutations or variants of uncertain significance were identified, and the mutation segregated with the disorder in the family. There was a range of clinical expression among the 10 family members from almost no NS4 characteristics to a typical presentation. The family was part of an NS cohort previously studied by van Trier et al. (2015). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>8 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 FIBROMATOSIS, GINGIVAL, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SOS1, 1-BP INS, 126142C
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906518,
|
|
|
|
|
|
|
|
ClinVar: RCV000013728, RCV002482863, RCV004589512, RCV004820821
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an extensive Brazilian family with hereditary gingival fibromatosis (GINGF1; 135300), Hart et al. (2002) demonstrated that the disorder was caused by insertion of a cytosine between nucleotides 126142 and 126143 in codon 1083 of the SOS1 gene. The insertion mutation introduced a frameshift and created a premature stop codon, abolishing 4 functionally important proline-rich SH3 binding domains normally present in the carboxyl-terminal region of the SOS1 protein. In the cDNA sequence, the insertion was between nucleotides 3248 and 3249. The mutation yielded a chimeric 1,105-amino acid protein that consisted of 1,083 SOS1 N-terminal amino acids in a normal sequence, followed by 22 replaced amino acids and a premature stop codon at codon 1106. </p>
|
|
</span>
|
|
</div>
|
|
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|
|
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<div>
|
|
<br />
|
|
</div>
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|
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</div>
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|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 NOONAN SYNDROME 4</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SOS1, THR266LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852812,
|
|
|
|
|
|
|
|
ClinVar: RCV000013729, RCV000038570, RCV000149833, RCV000213007, RCV000515403, RCV003450637
|
|
|
|
|
|
</span>
|
|
</div>
|
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|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 6-year-old girl with sporadic Noonan syndrome (NS4; 610733), Roberts et al. (2007) found a 797C-A transversion in exon 6 of the SOS1 gene that resulted in a thr266-to-lys substitution (T266K). The child had hypertrophic cardiomyopathy with thrombocytopenia and easy bruising. </p><p>Ferrero et al. (2008) reported a newborn with Noonan syndrome and the T266K mutation. The pregnancy was characterized by polyhydramnios and increased fetal nuchal translucency. Dysmorphic facial features included hypertelorism, epicanthal folds, flat nasal bridge, low-set posteriorly rotated ears, and short neck. Other features included moderate pulmonic stenosis and bilateral cryptorchidism. Developmental milestones were normal at 24 months of age. There were no coagulation abnormalities. Ferrero et al. (2008) noted the phenotypic differences from the patient reported by Roberts et al. (2007). </p>
|
|
</span>
|
|
</div>
|
|
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|
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<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 NOONAN SYNDROME 4</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
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|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SOS1, MET269ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852813,
|
|
|
|
|
|
|
|
ClinVar: RCV000013730, RCV000157691, RCV000211854, RCV000554031, RCV000856805, RCV002415412
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 patients with sporadic Noonan syndrome (NS4; 610733), Roberts et al. (2007) detected an 806T-G transversion in the SOS1 gene that caused a met269-to-arg (M269R) substitution. One of the patients was a 7-year-old boy with pulmonic stenosis and hypertrophic cardiomyopathy, easy bruising, and cryptorchidism with inguinal hernia. The other was an 11-year-old boy with pulmonic stenosis and atrial septal defect and cryptorchidism. School placement was regular in both cases. Tartaglia et al. (2007) identified the same mutation in 1 patient, also a sporadic case. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
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<br />
|
|
</div>
|
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|
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</div>
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|
|
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<div>
|
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 NOONAN SYNDROME 4</strong>
|
|
</span>
|
|
</h4>
|
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</div>
|
|
|
|
|
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
SOS1, ARG552GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852814,
|
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|
|
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gnomAD: rs137852814,
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ClinVar: RCV000013731, RCV000156980, RCV000157693, RCV000159174, RCV000515160, RCV002399321
|
|
|
|
|
|
</span>
|
|
</div>
|
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|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 41-year-old father and his infant son, Roberts et al. (2007) found that Noonan syndrome (NS4; 610733) was associated with a missense mutation in the SOS1 gene: an arg552-to-gly substitution (R552G) caused by a 1654A-G transition. The son had pulmonic stenosis. The father had cryptorchidism. Both showed 25 to 50% normal linear growth. Tartaglia et al. (2007) identified this mutation in 2 de novo cases. </p>
|
|
</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>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 NOONAN SYNDROME 4</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
SOS1, ARG552SER
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|
|
|
|
|
<br />
|
|
|
|
SNP: rs267607079,
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|
|
|
|
|
|
|
ClinVar: RCV000013732, RCV000038525, RCV000149832, RCV000156992, RCV000159177, RCV000213008, RCV000515298, RCV000654947, RCV000763086, RCV000787997, RCV000787998, RCV000856746, RCV002250500, RCV002399362, RCV003128391
|
|
|
|
|
|
</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a girl with Noonan syndrome-4 (NS4; 610733) who had pigmented villonodular synovitis (PVNS), Mascheroni et al. (2008) identified a de novo heterozygous mutation in the SOS1 gene, resulting in an arg552-to-ser (R522S) substitution. She presented at 13 years with swelling and severe pain in her right foot and ankle. History and physical examination showed that she had multiple features of Noonan syndrome. Mascheroni et al. (2008) suggested that PVNS is a proliferative lesion that is part of the phenotypic spectrum of Noonan syndrome. Another mutation in this same codon (R552G; 182530.0004) has also been reported. </p>
|
|
</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>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0006 NOONAN SYNDROME 4</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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SOS1, TRP432ARG
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<br />
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SNP: rs267607080,
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ClinVar: RCV000013733, RCV000159161, RCV000211853, RCV000818949
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 brothers, born of consanguineous parents, with Noonan syndrome-4 (NS4; 610733) and multiple giant cell lesions, Hanna et al. (2009) identified a heterozygous 1294T-C transition in exon 10 of the SOS1 gene, resulting in a trp432-to-arg (W432R) substitution within the pleckstrin homology domain. One boy presented at age 4.5 years with a 2-year history of bilateral progressive swelling of the mandible. Radiographic studies showed multilocular lesions of the mandibular rami, consistent with giant cell lesions. The boy's 6.5-year-old brother presented with severe pulmonary valvular stenosis and was found to have similar multilocular lesions of the mandible as his brother. Both boys had characteristic facial features of Noonan syndrome, including high anterior hairline with frontal bossing, follicular hyperkeratosis of the forehead (keratosis pilaris), depressed nasal bridge, hypertelorism, downslanting palpebral fissures, and low-set and posteriorly angulated ears with thick helices. Other features included short neck and widely spaced nipples. Both showed normal development and normal stature. The father showed milder features of the disorder, with long face, downslanting palpebral fissures, low-set ears, and widely spaced nipples, and was also heterozygous for the W432R mutation. </p>
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</span>
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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>
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<h4>
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<span class="mim-font">
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<strong>.0007 NOONAN SYNDROME 4</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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SOS1, PRO1045ARG
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<br />
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SNP: rs1668859370,
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ClinVar: RCV001200895
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 10 affected members of a 3-generation family segregating Noonan syndrome-4 (NS4; 610733), van Trier et al. (2017) identified a heterozygous c.3134C-G transversion (c.3134C-G, NM_005633.3) in the SOS1 gene, resulting in a pro1045-to-arg (P1045R) substitution at a moderately conserved residue. The mutation was identified in the proband (patient IV-8) by next-generation sequencing of an NS gene panel and in additional family members by Sanger sequencing. No other pathogenic mutations or variants of uncertain significance were identified, and the mutation segregated with the disorder in the family. There was a range of clinical expression among the 10 family members from almost no NS4 characteristics to a typical presentation. The family was part of an NS cohort previously studied by van Trier et al. (2015). </p>
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</span>
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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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<h4>
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<span class="mim-font">
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<strong>.0008 FIBROMATOSIS, GINGIVAL, 1</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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SOS1, 4-BP INS, 3265TAAC
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<br />
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ClinVar: RCV004776463
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a 14-year-old girl, her mother, and a maternal aunt (family D) with severe gingival overgrowth (GINGF1; 135300), Machado et al. (2023) identified heterozygosity for a 4-bp insertion (c.3265_3266insTAAC) in the SOS1 gene, causing a frameshift predicted to result in a premature termination codon (Pro1089LeufsTer). DNA was unavailable from unaffected family members for segregation analysis. </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>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Bowtell, D., Fu, P., Simon, M. A., Senior, P.
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<strong>Identification of murine homologues of the Drosophila Son of sevenless gene: potential activators of ras.</strong>
|
|
Proc. Nat. Acad. Sci. 89: 6511-6515, 1992.
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[PubMed: 1631150]
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[Full Text: https://doi.org/10.1073/pnas.89.14.6511]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Chardin, P., Camonis, J. H., Gale, N. W., Van Aelst, L., Schlessinger, J., Wigler, M. H., Bar-Sagi, D.
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<strong>Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2.</strong>
|
|
Science 260: 1338-1343, 1993.
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[PubMed: 8493579]
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[Full Text: https://doi.org/10.1126/science.8493579]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Ferrero, G. B., Baldassarre, G., Delmonaco, A. G., Biamino, E., Banaudi, E., Carta, C., Rossi, C., Silengo, M. C.
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<strong>Clinical and molecular characterization of 40 patients with Noonan syndrome.</strong>
|
|
Europ. J. Med. Genet. 51: 566-572, 2008.
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[PubMed: 18678287]
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[Full Text: https://doi.org/10.1016/j.ejmg.2008.06.011]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Hanna, N., Parfait, B., Talaat, I. M., Vidaud, M., Elsedfy, H. H.
|
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<strong>SOS1: a new player in the Noonan-like/multiple giant cell lesion syndrome.</strong>
|
|
Clin. Genet. 75: 568-571, 2009.
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[PubMed: 19438935]
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[Full Text: https://doi.org/10.1111/j.1399-0004.2009.01149.x]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Hart, T. C., Zhang, Y., Gorry, M. C., Hart, P. S., Cooper, M., Marazita, M. L., Marks, J. M., Cortelli, J. R., Pallos, D.
|
|
<strong>A mutation in the SOS1 gene causes hereditary gingival fibromatosis type 1.</strong>
|
|
Am. J. Hum. Genet. 70: 943-954, 2002.
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[PubMed: 11868160]
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[Full Text: https://doi.org/10.1086/339689]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Huang, W. Y. C., Alvarez, S., Kondo, Y., Lee, Y. K., Chung, J. K., Lam, H. Y. M., Biswas, K. H., Kuriyan, J., Groves, J. T.
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|
<strong>A molecular assembly phase transition and kinetic proofreading modulate Ras activation by SOS.</strong>
|
|
Science 363: 1098-1103, 2019.
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[PubMed: 30846600]
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[Full Text: https://doi.org/10.1126/science.aau5721]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Machado, R. A., de Andrade, R. S., Pego, S. P. B., Krepischi, A. C. V., Coletta, R. D., Martelli-Junior, H.
|
|
<strong>New evidence of genetic heterogeneity causing hereditary gingival fibromatosis and ALK and CD36 as new candidate genes.</strong>
|
|
J. Periodont. 94: 108-118, 2023.
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[PubMed: 35665929]
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[Full Text: https://doi.org/10.1002/JPER.22-0219]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Mascheroni, E., Digilio, M. C., Cortis, E., Devito, R., Sarkozy, A., Capolino, R., Dallapiccola, B., Ugazio, A. G.
|
|
<strong>Pigmented villonodular synovitis in a patient with Noonan syndrome and SOS1 gene mutation. (Letter)</strong>
|
|
Am. J. Med. Genet. 146A: 2966-2967, 2008.
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[PubMed: 18925667]
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[Full Text: https://doi.org/10.1002/ajmg.a.32538]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Roberts, A. E., Araki, T., Swanson, K. D., Montgomery, K. T., Schiripo, T. A., Joshi, V. A., Li, L., Yassin, Y., Tamburino, A. M., Neel, B. G., Kucherlapati, R. S.
|
|
<strong>Germline gain-of-function mutations in SOS1 cause Noonan syndrome.</strong>
|
|
Nature Genet. 39: 70-74, 2007.
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[PubMed: 17143285]
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[Full Text: https://doi.org/10.1038/ng1926]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Scita, G., Nordstrom, J., Carbone, R., Tenca, P., Giardina, G., Gutkind, S., Bjarnegard, M., Betsholtz, C., Di Fiore, P. P.
|
|
<strong>EPS8 and E3B1 transduce signals from Ras to Rac.</strong>
|
|
Nature 401: 290-293, 1999.
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[PubMed: 10499589]
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[Full Text: https://doi.org/10.1038/45822]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Sibilia, M., Fleischmann, A., Behrens, A., Stingl, L., Carroll, J., Watt, F. M., Schlessinger, J., Wagner, E. F.
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<strong>The EGF receptor provides an essential survival signal for SOS-dependent skin tumor development.</strong>
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Cell 102: 211-220, 2000.
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[PubMed: 10943841]
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[Full Text: https://doi.org/10.1016/s0092-8674(00)00026-x]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Soisson, S. M., Nimnual, A. S., Uy, M., Bar-Sagi, D., Kuriyan, J.
|
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<strong>Crystal structure of the Dbl and pleckstrin homology domains from the human Son of sevenless protein.</strong>
|
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Cell 95: 259-268, 1998.
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[PubMed: 9790532]
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[Full Text: https://doi.org/10.1016/s0092-8674(00)81756-0]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Tartaglia, M., Pennacchio, L. A., Zhao, C., Yadav, K. K., Fodale, V., Sarkozy, A., Pandit, B., Oishi, K., Martinelli, S., Schackwitz, W., Ustaszewska, A., Martin, J., and 13 others.
|
|
<strong>Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome.</strong>
|
|
Nature Genet. 39: 75-79, 2007. Note: Erratum: Nature Genet. 39: 276 only, 2007.
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[PubMed: 17143282]
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[Full Text: https://doi.org/10.1038/ng1939]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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van Trier, D. C., Rinne, T., Noordam, K., Draaisma, J. M., van der Burgt, I.
|
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<strong>Variable phenotypic expression in a large Noonan syndrome family segregating a novel SOS1 mutation.</strong>
|
|
Am. J. Med. Genet. 173A: 2968-2972, 2017.
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[PubMed: 28884940]
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[Full Text: https://doi.org/10.1002/ajmg.a.38466]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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van Trier, D. C., van Nierop, J., Draaisma, J. M., van der Burgt, I., Kunst, H., Croonen, E. A., Admiraal, R. J. C.
|
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<strong>External ear anomalies and hearing impairment in Noonan syndrome.</strong>
|
|
Int. J. Pediat. Otorhinolaryng. 79: 874-878, 2015.
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[PubMed: 25862627]
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[Full Text: https://doi.org/10.1016/j.ijporl.2015.03.021]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Webb, G. C., Jenkins, N. A., Largaespada, D. A., Copeland, N. G., Fernandez, C. S., Bowtell, D. D. L.
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<strong>Mammalian homologues of the Drosophila Son of sevenless gene map to murine chromosomes 17 and 12 and to human chromosomes 2 and 14, respectively.</strong>
|
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Genomics 18: 14-19, 1993.
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[PubMed: 8276400]
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[Full Text: https://doi.org/10.1006/geno.1993.1421]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Zenker, M., Horn, D., Wieczorek, D., Allanson, J., Pauli, S., van der Burgt, I., Doerr, H.-G., Gaspar, H., Hofbeck, M., Gillessen-Kaesbach, G., Koch, A., Meinecke, P., and 13 others.
|
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<strong>SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome. (Letter)</strong>
|
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J. Med. Genet. 44: 651-656, 2007.
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[PubMed: 17586837]
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[Full Text: https://doi.org/10.1136/jmg.2007.051276]
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</p>
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</li>
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</ol>
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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 class="row">
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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<span class="text-nowrap mim-text-font">
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Contributors:
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</span>
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</div>
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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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Marla J. F. O'Neill - updated : 10/31/2024<br>Hilary J. Vernon - updated : 07/07/2020<br>Ada Hamosh - updated : 10/01/2019<br>Cassandra L. Kniffin - updated : 6/1/2010<br>Cassandra L. Kniffin - updated : 6/18/2009<br>Cassandra L. Kniffin - updated : 3/3/2009<br>Victor A. McKusick - updated : 12/28/2007<br>Victor A. McKusick - updated : 1/30/2007<br>Victor A. McKusick - updated : 4/12/2002<br>Stylianos E. Antonarakis - updated : 8/8/2000<br>Ada Hamosh - updated : 2/14/2000<br>Stylianos E. Antonarakis - updated : 11/6/1998<br>Alan F. Scott - updated : 5/5/1996
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</span>
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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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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Victor A. McKusick : 6/22/1993
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Edit History:
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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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alopez : 10/31/2024<br>carol : 07/07/2020<br>alopez : 10/01/2019<br>carol : 08/22/2019<br>carol : 10/01/2015<br>carol : 9/23/2015<br>terry : 4/9/2012<br>carol : 9/29/2011<br>wwang : 11/5/2010<br>ckniffin : 10/26/2010<br>wwang : 10/6/2010<br>wwang : 6/4/2010<br>ckniffin : 6/1/2010<br>wwang : 7/21/2009<br>ckniffin : 6/18/2009<br>wwang : 3/10/2009<br>ckniffin : 3/3/2009<br>alopez : 8/20/2008<br>alopez : 1/25/2008<br>terry : 12/28/2007<br>terry : 8/6/2007<br>alopez : 2/19/2007<br>alopez : 1/31/2007<br>terry : 1/30/2007<br>alopez : 4/25/2002<br>alopez : 4/25/2002<br>cwells : 4/19/2002<br>terry : 4/12/2002<br>alopez : 1/9/2002<br>mgross : 8/8/2000<br>mgross : 8/8/2000<br>alopez : 3/3/2000<br>alopez : 2/14/2000<br>carol : 9/20/1999<br>psherman : 11/13/1998<br>psherman : 11/6/1998<br>alopez : 7/13/1998<br>terry : 5/7/1996<br>mark : 5/7/1996<br>mark : 5/5/1996<br>mark : 5/5/1996<br>carol : 11/8/1994<br>carol : 6/22/1993
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