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Entry
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- *608435 - MUSCLE RAS VIRAL ONCOGENE HOMOLOG; MRAS
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- OMIM
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<p>
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<span class="h4">*608435</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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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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<a href="#geneFunction">Gene Function</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="#molecularGenetics">Molecular Genetics</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/608435">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 role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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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=ENSG00000158186;t=ENST00000423968" 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=22808" 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=608435" 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=ENSG00000158186;t=ENST00000423968" 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_001085049,NM_001252090,NM_001252091,NM_001252092,NM_001252093,NM_012219,XM_005247228,XM_005247229,XM_024453396,XM_047447695,XM_047447696,XM_047447697,XM_047447698,XM_047447699" 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_001085049" 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=608435" 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=06662&isoform_id=06662_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/MRAS" 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/3228374,4105178,6226045,17389388,20147729,49457087,54696976,119599474,119599475,119599476,119599477,145386506,145386562,193784964,194380718,221045530,355390291,355390293,355390295,355390297,530374150,530374152,1370483463,2217342578,2217342581,2217342583,2217342585,2217342587,2462588035,2462588038,2462588040,2462588042,2462588044" 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/O14807" 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=22808" 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=ENSG00000158186;t=ENST00000423968" 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=MRAS" 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=MRAS" 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+22808" 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/MRAS" 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:22808" 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/22808" 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=chr3&hgg_gene=ENST00000423968.7&hgg_start=138347648&hgg_end=138405535&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/genes/HGNC:7227" 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://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=608435[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=608435[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/MRAS/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/ENSG00000158186" 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=MRAS" 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=MRAS" 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=MRAS" 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=MRAS&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/PA30932" 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:7227" 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://www.mousephenotype.org/data/genes/MGI:1100856" 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/MRAS#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:1100856" 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/22808/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=22808" 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=WBGene00004311;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-050208-495" 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">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:22808" 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=MRAS&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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608435
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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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MUSCLE RAS VIRAL ONCOGENE HOMOLOG; MRAS
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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RELATED RAS VIRAL ONCOGENE HOMOLOG 3; RRAS3
|
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
|
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<span class="mim-text-font">
|
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=MRAS" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">MRAS</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
|
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Cytogenetic location: <a href="/geneMap/3/718?start=-3&limit=10&highlight=718">3q22.3</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr3:138347648-138405535&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'})">3:138,347,648-138,405,535</a> </span>
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</em>
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</strong>
|
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</div>
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<div>
|
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
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<tr class="active">
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<th>
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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="1">
|
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<span class="mim-font">
|
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<a href="/geneMap/3/718?start=-3&limit=10&highlight=718">
|
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3q22.3
|
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</a>
|
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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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Noonan syndrome 11
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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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|
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<a href="/entry/618499"> 618499 </a>
|
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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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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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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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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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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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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
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<ul class="dropdown-menu" style="width: 17em;">
|
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<li><a href="/graph/linear/608435" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/608435" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></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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<a id="text" class="mim-anchor"></a>
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<h4>
|
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<span class="mim-font">
|
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
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<strong>TEXT</strong>
|
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</span>
|
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</span>
|
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</h4>
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<div>
|
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<a id="description" class="mim-anchor"></a>
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<p>Members of the RAS superfamily of GTP-binding proteins, which includes MRAS, are membrane-anchored, intracellular signal transducers responsible for a variety of normal cellular functions. They are oncogenically activated in a significant fraction of tumors (summary by <a href="#4" class="mim-tip-reference" title="Kimmelman, A., Tolkacheva, T., Lorenzi, M. V., Osada, M., Chan, A. M.-L. <strong>Identification and characterization of R-ras3: a novel member of the RAS gene family with a non-ubiquitous pattern of tissue distribution.</strong> Oncogene 15: 2675-2685, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9400994/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9400994</a>] [<a href="https://doi.org/10.1038/sj.onc.1201674" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9400994">Kimmelman et al., 1997</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9400994" 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="#6" class="mim-tip-reference" title="Matsumoto, K., Asano, T., Endo, T. <strong>Novel small GTPase M-Ras participates in reorganization of actin cytoskeleton.</strong> Oncogene 15: 2409-2417, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9395237/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9395237</a>] [<a href="https://doi.org/10.1038/sj.onc.1201416" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9395237">Matsumoto et al. (1997)</a> cloned rat and mouse Mras. Mras contains motifs for GDP/GTP binding and a C-terminal motif that mediates membrane attachment by a geranylgeranyl group in combination with a polybasic region. Northern blot analysis detected transcripts of 4.2 and 1.7 kb in mouse brain and in mouse myoblast cell line C2. Expression of the 4.2-kb transcript was high in brain and low in C2 myoblasts, whereas expression of the 1.7-kb transcript was low in both brain and C2 myoblasts. RT-PCR detected expression of mouse Mras in C2 myotubes, fibroblasts, skeletal muscle, heart, and uterus. Epitope-tagged Mras was expressed in mouse fibroblasts on plasma membrane-associated structures, including microspikes, membrane ruffles, and pseudopods. It was also diffusely distributed throughout the cytoplasm. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9395237" 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="#4" class="mim-tip-reference" title="Kimmelman, A., Tolkacheva, T., Lorenzi, M. V., Osada, M., Chan, A. M.-L. <strong>Identification and characterization of R-ras3: a novel member of the RAS gene family with a non-ubiquitous pattern of tissue distribution.</strong> Oncogene 15: 2675-2685, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9400994/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9400994</a>] [<a href="https://doi.org/10.1038/sj.onc.1201674" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9400994">Kimmelman et al. (1997)</a> identified rat Mras, which they designated Rras3, through sequence similarity with RRAS (<a href="/entry/165090">165090</a>) and RRAS2 (<a href="/entry/600098">600098</a>). By searching an EST database using rat Mras as query, followed by PCR of an embryonic lung fibroblast cDNA library, they cloned human MRAS. The deduced 208-amino acid protein has a calculated molecular mass of 23.8 kD. Unlike other RAS oncogenes, MRAS contains an N-terminal extension of 10 amino acids, which is followed by the conserved 117-amino acid catalytic domain and a C-terminal membrane localization domain. MRAS shares 75% amino acid identity with RRAS2. Northern blot analysis of several human tissues detected a transcript of about 3.8 kb expressed at high levels in brain and heart, but not in other tissues examined. In vitro translation of MRAS cDNA resulted in a protein with an apparent molecular mass of 27 kD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9400994" 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>Using mouse Mras as probe, <a href="#5" class="mim-tip-reference" title="Louahed, J., Grasso, L., De Smet, C., Van Roost, E., Wildmann, C., Nicolaides, N. C., Levitt, R. C., Renauld, J.-C. <strong>Interleukin-9-induced expression of M-Ras/R-Ras3 oncogene in T-helper clones.</strong> Blood 94: 1701-1710, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10477695/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10477695</a>]" pmid="10477695">Louahed et al. (1999)</a> cloned MRAS from a brain cDNA library, and they isolated several clones from a testis cDNA library. Mouse and human MRAS share 97% amino acid identity. <a href="#5" class="mim-tip-reference" title="Louahed, J., Grasso, L., De Smet, C., Van Roost, E., Wildmann, C., Nicolaides, N. C., Levitt, R. C., Renauld, J.-C. <strong>Interleukin-9-induced expression of M-Ras/R-Ras3 oncogene in T-helper clones.</strong> Blood 94: 1701-1710, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10477695/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10477695</a>]" pmid="10477695">Louahed et al. (1999)</a> identified a C-terminal consensus prenylation signal, as well as the polybasic region that likely mediates electrostatic interaction with acidic phospholipids on the inner membrane, in MRAS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10477695" 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="#6" class="mim-tip-reference" title="Matsumoto, K., Asano, T., Endo, T. <strong>Novel small GTPase M-Ras participates in reorganization of actin cytoskeleton.</strong> Oncogene 15: 2409-2417, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9395237/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9395237</a>] [<a href="https://doi.org/10.1038/sj.onc.1201416" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9395237">Matsumoto et al. (1997)</a> assayed bacterially expressed mouse Mras and found that it bound and hydrolyzed GTP. Transfection of Mras cDNA and microinjection of a constitutively active form of Mras protein into fibroblasts induced formation of peripheral microspikes. Actin stress fibers disappeared, and numerous actin foci were formed in the injected cells. The transfected cells eventually exhibited dendritic appearance with microspikes. <a href="#6" class="mim-tip-reference" title="Matsumoto, K., Asano, T., Endo, T. <strong>Novel small GTPase M-Ras participates in reorganization of actin cytoskeleton.</strong> Oncogene 15: 2409-2417, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9395237/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9395237</a>] [<a href="https://doi.org/10.1038/sj.onc.1201416" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9395237">Matsumoto et al. (1997)</a> concluded that Mras participates in reorganization of the actin cytoskeleton. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9395237" 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="#4" class="mim-tip-reference" title="Kimmelman, A., Tolkacheva, T., Lorenzi, M. V., Osada, M., Chan, A. M.-L. <strong>Identification and characterization of R-ras3: a novel member of the RAS gene family with a non-ubiquitous pattern of tissue distribution.</strong> Oncogene 15: 2675-2685, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9400994/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9400994</a>] [<a href="https://doi.org/10.1038/sj.onc.1201674" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9400994">Kimmelman et al. (1997)</a> found that mouse fibroblasts transfected with a constitutively active MRAS mutant formed transformed foci that showed spindle-shaped morphology. Transformed cells also readily proliferated under low-serum conditions and showed anchorage-independent growth in semisolid agarose. MRAS weakly stimulated mitogen-activated protein kinase (MAPK) activity, and this effect was potentiated by coexpression of RAF1 (<a href="/entry/164760">164760</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9400994" 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="#7" class="mim-tip-reference" title="Quilliam, L. A., Castro, A. F., Rogers-Graham, K. S., Martin, C. B., Der, C. J., Bi, C. <strong>M-Ras/R-Ras3, a transforming Ras protein regulated by Sos1, GRF1, and p120 Ras GTPase-activating protein, interacts with the putative Ras effector AF6.</strong> J. Biol. Chem. 274: 23850-23857, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10446149/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10446149</a>] [<a href="https://doi.org/10.1074/jbc.274.34.23850" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10446149">Quilliam et al. (1999)</a> found that expression of a mutationally activated mouse Mras in fibroblasts resulted in cellular transformation, and expression in myoblasts inhibited differentiation. Mras cooperated with Raf, Rac (see <a href="/entry/602048">602048</a>), and Rho (see <a href="/entry/165390">165390</a>) to induce transforming foci in fibroblasts. The Mras GTP/GDP cycle was sensitive to the inclusion of Sos1 (<a href="/entry/182530">182530</a>), Grf1 (<a href="/entry/606600">606600</a>), and p120 RasGAP (<a href="/entry/139150">139150</a>). Mras also immunoprecipitated with Af6 (<a href="/entry/159559">159559</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10446149" 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>By representational difference analysis, <a href="#5" class="mim-tip-reference" title="Louahed, J., Grasso, L., De Smet, C., Van Roost, E., Wildmann, C., Nicolaides, N. C., Levitt, R. C., Renauld, J.-C. <strong>Interleukin-9-induced expression of M-Ras/R-Ras3 oncogene in T-helper clones.</strong> Blood 94: 1701-1710, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10477695/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10477695</a>]" pmid="10477695">Louahed et al. (1999)</a> found that Mras expression was induced by interleukin-9 (IL9; <a href="/entry/146931">146931</a>) in a mouse T-helper cell clone. Induction seemed to depend upon the JAK (see <a href="/entry/147795">147795</a>)/STAT (see <a href="/entry/600555">600555</a>) pathway. In addition, IL3 (<a href="/entry/147740">147740</a>), but not IL9, increased GTP binding to Mras. A constitutively activated Mras mutant induced activation of Elk transcription factor (see <a href="/entry/311040">311040</a>) by triggering the MAPK pathway and allowed IL3-independent proliferation of the mouse pro-B cell line BaF3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10477695" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The MRAS GTPase, SHOC2 (<a href="/entry/602775">602775</a>), and protein phosphatase-1 (PP1; see <a href="/entry/176875">176875</a>) interact to form a heterotrimeric holoenzyme that dephosphorylates the S259 inhibitory site on RAF kinases, activating downstream signaling. <a href="#10" class="mim-tip-reference" title="Young, L. C., Hartig, N., del Rio, L. B., Sari, S., Ringham-Terry, B., Wainwright, J. R., Jones, G. G., McCormick, F., Rodriguez-Viciana, P. <strong>SHOC2-MRAS-PP1 complex positively regulates RAF activity and contributes to Noonan syndrome pathogenesis.</strong> Proc. Nat. Acad. Sci. 115: E10576-E10585, 2018. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30348783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30348783</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30348783[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.1720352115" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30348783">Young et al. (2018)</a> showed that MRAS and SHOC2 function as PP1 regulatory subunits, providing the complex with striking specificity against RAF. MRAS also functions as a targeting subunit, as membrane localization is required for efficient RAF dephosphorylation and ERK pathway regulation in cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30348783" 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="mim-changed mim-change"><p><a href="#8" class="mim-tip-reference" title="Stumpf, A. M. <strong>Personal Communication.</strong> Baltimore, Md. 2/12/2025."None>Stumpf (2025)</a> mapped the MRAS gene to chromosome 3q22.3 based on an alignment of the MRAS sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=BC035939" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">BC035939</a>) with the genomic sequence (GRCh38).</p></div>
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<p><a href="#3" class="mim-tip-reference" title="Higgins, E. M., Bos, J. M., Mason-Suares, H., Tester, D. J., Ackerman, J. P., MacRae, C. A., Sol-Church, K., Gripp, K. W., Urrutia, R., Ackerman, M. J. <strong>Elucidation of MRAS-mediated Noonan syndrome with cardiac hypertrophy.</strong> JCI Insight 2: e91225, 2017. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28289718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28289718</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28289718[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/10.1172/jci.insight.91225" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28289718">Higgins et al. (2017)</a> reported 2 patients with Noonan syndrome and concomitant cardiac hypertrophy (NS11; <a href="/entry/618499">618499</a>) who carried de novo heterozygous missense mutations in the MRAS gene. The first patient carried a gly23-to-val (G23V; <a href="#0001">608435.0001</a>) mutation and the second a thr68-to-ile mutation (T68I; <a href="#0002">608435.0002</a>). The mutations were identified by whole-exome sequencing and sequencing of the MRAS gene, respectively. The G23V mutation was studied extensively and found to result in a constitutively active form of MRAS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28289718" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Suzuki, H., Takenouchi, T., Uehara, T., Takasago, S., Ihara, S., Yoshihashi, H., Kosaki, K. <strong>Severe Noonan syndrome phenotype associated with a germline Q71R MRAS variant: a recurrent substitution in RAS homologs in various cancers.</strong> Am. J. Med. Genet. 179A: 1628-1630, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31173466/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31173466</a>] [<a href="https://doi.org/10.1002/ajmg.a.61261" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31173466">Suzuki et al. (2019)</a> reported a patient with a severe Noonan phenotype including hypertrophic cardiomyopathy who was heterozygous for a de novo gln71-to-arg (Q71R; <a href="#0003">608435.0003</a>) mutation in MRAS. The authors noted that gln71 is highly conserved from zebrafish to humans, and that gln71 of MRAS corresponds to gln61 of HRAS (<a href="/entry/190020">190020</a>), KRAS (<a href="/entry/190070">190070</a>), and NRAS (<a href="/entry/164790">164790</a>), within the nucleotide-binding switch II region critical for the activation of proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31173466" 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>MRAS, a close relative of RAS oncoproteins, interacts with SHOC2 (<a href="/entry/602775">602775</a>) and protein phosphatase-1 (PP1; see <a href="/entry/176875">176875</a>) to form a heterotrimeric holoenzyme that dephosphorylates an inhibitory site on RAF kinases, activating downstream signaling. <a href="#10" class="mim-tip-reference" title="Young, L. C., Hartig, N., del Rio, L. B., Sari, S., Ringham-Terry, B., Wainwright, J. R., Jones, G. G., McCormick, F., Rodriguez-Viciana, P. <strong>SHOC2-MRAS-PP1 complex positively regulates RAF activity and contributes to Noonan syndrome pathogenesis.</strong> Proc. Nat. Acad. Sci. 115: E10576-E10585, 2018. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30348783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30348783</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30348783[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.1720352115" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30348783">Young et al. (2018)</a> showed that the MRAS mutation G23V (equivalent to the oncogenic G13V in classical RAS proteins), like MRAS Q71L (Q61L in RAS), shows increased interaction with other effectors such as BRAF (<a href="/entry/164757">164757</a>), CRAF (RAF1; <a href="/entry/164760">164760</a>), and AF6 (MLLT4; <a href="/entry/159559">159559</a>), consistent with activating mutations leading to GTP-loading of MRAS. On the other hand, the T68I mutation, which is located in switch II, did not stimulate binding to BRAF or CRAF. This suggested that, while MRAS G23V can drive RAF activation through both direct binding and complex formation with SHOC2-PP1, the MRAS T68I substitution discriminates between effectors, selecting specifically for interaction with SHOC2 and PP1 and thus the RAF phosphatase function of MRAS. <a href="#10" class="mim-tip-reference" title="Young, L. C., Hartig, N., del Rio, L. B., Sari, S., Ringham-Terry, B., Wainwright, J. R., Jones, G. G., McCormick, F., Rodriguez-Viciana, P. <strong>SHOC2-MRAS-PP1 complex positively regulates RAF activity and contributes to Noonan syndrome pathogenesis.</strong> Proc. Nat. Acad. Sci. 115: E10576-E10585, 2018. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30348783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30348783</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30348783[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.1720352115" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30348783">Young et al. (2018)</a> showed that mutations in MRAS, SHOC2, and PPP1CB (<a href="/entry/600590">600590</a>) that result in Noonan syndrome invariably promote complex formation with each other, but not necessarily with other interactors. Thus, Noonan syndrome in individuals with SHOC2, MRAS, or PPPC1B mutations is likely driven at the biochemical level by enhanced ternary complex formation and highlights the crucial role of this phosphatase holoenzyme in RAF S259 dephosphorylation, ERK pathway dynamics, and normal human development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30348783" 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=608435[MIM]" class="btn btn-default mim-tip-hint" role="button" 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>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1576359216 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1576359216;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=rs1576359216" 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=rs1576359216" 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=RCV000787303 OR RCV003155311 OR RCV005092354" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000787303, RCV003155311, RCV005092354" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000787303...</a>
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<p>In a 15-year-old girl with Noonan syndrome-11 (NS11; <a href="/entry/618499">618499</a>), <a href="#3" class="mim-tip-reference" title="Higgins, E. M., Bos, J. M., Mason-Suares, H., Tester, D. J., Ackerman, J. P., MacRae, C. A., Sol-Church, K., Gripp, K. W., Urrutia, R., Ackerman, M. J. <strong>Elucidation of MRAS-mediated Noonan syndrome with cardiac hypertrophy.</strong> JCI Insight 2: e91225, 2017. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28289718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28289718</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28289718[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/10.1172/jci.insight.91225" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28289718">Higgins et al. (2017)</a> identified a heterozygous c.68G-T transversion (c.68G-T, NM_012219) in the MRAS gene resulting in a glycine-to-valine substitution at codon 23 (G23V). This variant occurred as a de novo event and was not seen in over 280,000 alleles in gnomAD. In silico and structural analyses predicted that this variant would result in constitutive activation of the protein. Biochemical studies showed a 40-fold increase in GTP loading, as well as increased ERK activation and signaling and transcription activation in response to growth factors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28289718" 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="#10" class="mim-tip-reference" title="Young, L. C., Hartig, N., del Rio, L. B., Sari, S., Ringham-Terry, B., Wainwright, J. R., Jones, G. G., McCormick, F., Rodriguez-Viciana, P. <strong>SHOC2-MRAS-PP1 complex positively regulates RAF activity and contributes to Noonan syndrome pathogenesis.</strong> Proc. Nat. Acad. Sci. 115: E10576-E10585, 2018. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30348783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30348783</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30348783[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.1720352115" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30348783">Young et al. (2018)</a> showed that the MRAS mutation G23V, equivalent to the oncogenic G13V in classical RAS proteins, showed increased interaction with other effectors such as BRAF (<a href="/entry/164757">164757</a>), CRAF (RAF1; <a href="/entry/164760">164760</a>), and AF6 (MLLT4; <a href="/entry/159559">159559</a>), consistent with activating mutations leading to GTP-loading of MRAS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30348783" 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">rs1576387876 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1576387876;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=rs1576387876" 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=rs1576387876" 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=RCV000787304 OR RCV002536888 OR RCV004732489" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000787304, RCV002536888, RCV004732489" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000787304...</a>
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<p>In a 6-year-old girl with Noonan syndrome-11 (NS11; <a href="/entry/618499">618499</a>), <a href="#3" class="mim-tip-reference" title="Higgins, E. M., Bos, J. M., Mason-Suares, H., Tester, D. J., Ackerman, J. P., MacRae, C. A., Sol-Church, K., Gripp, K. W., Urrutia, R., Ackerman, M. J. <strong>Elucidation of MRAS-mediated Noonan syndrome with cardiac hypertrophy.</strong> JCI Insight 2: e91225, 2017. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28289718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28289718</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28289718[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/10.1172/jci.insight.91225" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28289718">Higgins et al. (2017)</a> identified a heterozygous c.203C-T transition (c.203C-T, NM_012219) in the MRAS gene resulting in a threonine-to-isoleucine substitution at codon 68 (T68I). This variant occurred as a de novo event and was not seen in gnomAD. In silico analyses predicted that this was a deleterious mutation, but no functional assays were performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28289718" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a 2-year-old Japanese boy with a severe Noonan syndrome phenotype that included hypertrophic cardiomyopathy (NS11; <a href="/entry/618499">618499</a>), <a href="#9" class="mim-tip-reference" title="Suzuki, H., Takenouchi, T., Uehara, T., Takasago, S., Ihara, S., Yoshihashi, H., Kosaki, K. <strong>Severe Noonan syndrome phenotype associated with a germline Q71R MRAS variant: a recurrent substitution in RAS homologs in various cancers.</strong> Am. J. Med. Genet. 179A: 1628-1630, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31173466/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31173466</a>] [<a href="https://doi.org/10.1002/ajmg.a.61261" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31173466">Suzuki et al. (2019)</a> detected a heterozygous de novo c.212A-G transition (c.212A-G, NM_001085049.2) in the MRAS gene that resulted in a glutamine-to-arginine substitution at codon 71 (Q71R). This variant was not seen in gnomAD (<a href="#2" class="mim-tip-reference" title="Hamosh, A. <strong>Personal Communication.</strong> Baltimore, Md. 07/07/2019."None>Hamosh, 2019</a>). The Q71 codon in MRAS corresponds to the Q61 codon in classical RAS proteins, and <a href="#9" class="mim-tip-reference" title="Suzuki, H., Takenouchi, T., Uehara, T., Takasago, S., Ihara, S., Yoshihashi, H., Kosaki, K. <strong>Severe Noonan syndrome phenotype associated with a germline Q71R MRAS variant: a recurrent substitution in RAS homologs in various cancers.</strong> Am. J. Med. Genet. 179A: 1628-1630, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31173466/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31173466</a>] [<a href="https://doi.org/10.1002/ajmg.a.61261" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31173466">Suzuki et al. (2019)</a> stated that studies of the Q61R mutation in NRAS (<a href="/entry/164790#0002">164790.0002</a>) had found a GTP hydrolysis rate that was drastically slower than that of wildtype (<a href="#1" class="mim-tip-reference" title="Burd, C. E., Liu, W., Huynh, M. V., Waqas, M. A., Gillahan, J. E., Clark, K. S., Fu, K., Martin, B. L., Jeck, W. R., Souroullas, G. P., Darr, D. B., Zedek, D. C., Miley, M. J., Baguley, B. C., Campbell, S. L., Sharpless, N. E. <strong>Mutation-specific RAS oncogenicity explains NRAS codon 61 selection in melanoma.</strong> Cancer Discov. 4: 1418-1429, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25252692/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25252692</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25252692[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/10.1158/2159-8290.CD-14-0729" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25252692">Burd et al., 2014</a>). The Q71R mutation occurs in the nucleotide-binding switch II region of MRAS, critical for protein activation. Functional assays were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=25252692+31173466" 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="#10" class="mim-tip-reference" title="Young, L. C., Hartig, N., del Rio, L. B., Sari, S., Ringham-Terry, B., Wainwright, J. R., Jones, G. G., McCormick, F., Rodriguez-Viciana, P. <strong>SHOC2-MRAS-PP1 complex positively regulates RAF activity and contributes to Noonan syndrome pathogenesis.</strong> Proc. Nat. Acad. Sci. 115: E10576-E10585, 2018. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30348783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30348783</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30348783[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.1720352115" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30348783">Young et al. (2018)</a> showed that the MRAS mutation Q71L, equivalent to Q61L in classical RAS proteins, shows increased interaction with other effectors such as BRAF (<a href="/entry/164757">164757</a>), CRAF (RAF1; <a href="/entry/164760">164760</a>), and AF6 (MLLT4; <a href="/entry/159559">159559</a>), consistent with activating mutations leading to GTP-loading of MRAS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30348783" 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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Burd, C. E., Liu, W., Huynh, M. V., Waqas, M. A., Gillahan, J. E., Clark, K. S., Fu, K., Martin, B. L., Jeck, W. R., Souroullas, G. P., Darr, D. B., Zedek, D. C., Miley, M. J., Baguley, B. C., Campbell, S. L., Sharpless, N. E.
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<strong>Mutation-specific RAS oncogenicity explains NRAS codon 61 selection in melanoma.</strong>
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Cancer Discov. 4: 1418-1429, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25252692/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25252692</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25252692[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=25252692" 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/10.1158/2159-8290.CD-14-0729" target="_blank">Full Text</a>]
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Hamosh, A.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 07/07/2019.
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Higgins, E. M., Bos, J. M., Mason-Suares, H., Tester, D. J., Ackerman, J. P., MacRae, C. A., Sol-Church, K., Gripp, K. W., Urrutia, R., Ackerman, M. J.
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<strong>Elucidation of MRAS-mediated Noonan syndrome with cardiac hypertrophy.</strong>
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JCI Insight 2: e91225, 2017. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28289718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28289718</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28289718[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=28289718" 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/10.1172/jci.insight.91225" target="_blank">Full Text</a>]
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Kimmelman, A., Tolkacheva, T., Lorenzi, M. V., Osada, M., Chan, A. M.-L.
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<strong>Identification and characterization of R-ras3: a novel member of the RAS gene family with a non-ubiquitous pattern of tissue distribution.</strong>
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Oncogene 15: 2675-2685, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9400994/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9400994</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9400994" 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/sj.onc.1201674" target="_blank">Full Text</a>]
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Louahed, J., Grasso, L., De Smet, C., Van Roost, E., Wildmann, C., Nicolaides, N. C., Levitt, R. C., Renauld, J.-C.
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<strong>Interleukin-9-induced expression of M-Ras/R-Ras3 oncogene in T-helper clones.</strong>
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Blood 94: 1701-1710, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10477695/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10477695</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10477695" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Matsumoto, K., Asano, T., Endo, T.
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<strong>Novel small GTPase M-Ras participates in reorganization of actin cytoskeleton.</strong>
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Oncogene 15: 2409-2417, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9395237/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9395237</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9395237" 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/sj.onc.1201416" target="_blank">Full Text</a>]
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Quilliam, L. A., Castro, A. F., Rogers-Graham, K. S., Martin, C. B., Der, C. J., Bi, C.
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<strong>M-Ras/R-Ras3, a transforming Ras protein regulated by Sos1, GRF1, and p120 Ras GTPase-activating protein, interacts with the putative Ras effector AF6.</strong>
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J. Biol. Chem. 274: 23850-23857, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10446149/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10446149</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10446149" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Stumpf, A. M.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 2/12/2025.
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Suzuki, H., Takenouchi, T., Uehara, T., Takasago, S., Ihara, S., Yoshihashi, H., Kosaki, K.
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<strong>Severe Noonan syndrome phenotype associated with a germline Q71R MRAS variant: a recurrent substitution in RAS homologs in various cancers.</strong>
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Am. J. Med. Genet. 179A: 1628-1630, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31173466/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31173466</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31173466" 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.61261" target="_blank">Full Text</a>]
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Young, L. C., Hartig, N., del Rio, L. B., Sari, S., Ringham-Terry, B., Wainwright, J. R., Jones, G. G., McCormick, F., Rodriguez-Viciana, P.
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<strong>SHOC2-MRAS-PP1 complex positively regulates RAF activity and contributes to Noonan syndrome pathogenesis.</strong>
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Proc. Nat. Acad. Sci. 115: E10576-E10585, 2018. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30348783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30348783</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30348783[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=30348783" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Anne M. Stumpf - updated : 02/12/2025
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carol : 10/16/2019<br>carol : 07/12/2019<br>alopez : 07/11/2019<br>alopez : 07/11/2019<br>carol : 12/29/2011<br>wwang : 3/26/2009<br>mgross : 1/30/2004
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RELATED RAS VIRAL ONCOGENE HOMOLOG 3; RRAS3
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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: MRAS</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: 3q22.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 3:138,347,648-138,405,535 </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="1">
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<span class="mim-font">
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3q22.3
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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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Noonan syndrome 11
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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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618499
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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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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">
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3
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</span>
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</td>
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</tr>
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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>Members of the RAS superfamily of GTP-binding proteins, which includes MRAS, are membrane-anchored, intracellular signal transducers responsible for a variety of normal cellular functions. They are oncogenically activated in a significant fraction of tumors (summary by Kimmelman et al., 1997). </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">
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<strong>Cloning and Expression</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>Matsumoto et al. (1997) cloned rat and mouse Mras. Mras contains motifs for GDP/GTP binding and a C-terminal motif that mediates membrane attachment by a geranylgeranyl group in combination with a polybasic region. Northern blot analysis detected transcripts of 4.2 and 1.7 kb in mouse brain and in mouse myoblast cell line C2. Expression of the 4.2-kb transcript was high in brain and low in C2 myoblasts, whereas expression of the 1.7-kb transcript was low in both brain and C2 myoblasts. RT-PCR detected expression of mouse Mras in C2 myotubes, fibroblasts, skeletal muscle, heart, and uterus. Epitope-tagged Mras was expressed in mouse fibroblasts on plasma membrane-associated structures, including microspikes, membrane ruffles, and pseudopods. It was also diffusely distributed throughout the cytoplasm. </p><p>Kimmelman et al. (1997) identified rat Mras, which they designated Rras3, through sequence similarity with RRAS (165090) and RRAS2 (600098). By searching an EST database using rat Mras as query, followed by PCR of an embryonic lung fibroblast cDNA library, they cloned human MRAS. The deduced 208-amino acid protein has a calculated molecular mass of 23.8 kD. Unlike other RAS oncogenes, MRAS contains an N-terminal extension of 10 amino acids, which is followed by the conserved 117-amino acid catalytic domain and a C-terminal membrane localization domain. MRAS shares 75% amino acid identity with RRAS2. Northern blot analysis of several human tissues detected a transcript of about 3.8 kb expressed at high levels in brain and heart, but not in other tissues examined. In vitro translation of MRAS cDNA resulted in a protein with an apparent molecular mass of 27 kD. </p><p>Using mouse Mras as probe, Louahed et al. (1999) cloned MRAS from a brain cDNA library, and they isolated several clones from a testis cDNA library. Mouse and human MRAS share 97% amino acid identity. Louahed et al. (1999) identified a C-terminal consensus prenylation signal, as well as the polybasic region that likely mediates electrostatic interaction with acidic phospholipids on the inner membrane, in MRAS. </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>Gene Function</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>Matsumoto et al. (1997) assayed bacterially expressed mouse Mras and found that it bound and hydrolyzed GTP. Transfection of Mras cDNA and microinjection of a constitutively active form of Mras protein into fibroblasts induced formation of peripheral microspikes. Actin stress fibers disappeared, and numerous actin foci were formed in the injected cells. The transfected cells eventually exhibited dendritic appearance with microspikes. Matsumoto et al. (1997) concluded that Mras participates in reorganization of the actin cytoskeleton. </p><p>Kimmelman et al. (1997) found that mouse fibroblasts transfected with a constitutively active MRAS mutant formed transformed foci that showed spindle-shaped morphology. Transformed cells also readily proliferated under low-serum conditions and showed anchorage-independent growth in semisolid agarose. MRAS weakly stimulated mitogen-activated protein kinase (MAPK) activity, and this effect was potentiated by coexpression of RAF1 (164760). </p><p>Quilliam et al. (1999) found that expression of a mutationally activated mouse Mras in fibroblasts resulted in cellular transformation, and expression in myoblasts inhibited differentiation. Mras cooperated with Raf, Rac (see 602048), and Rho (see 165390) to induce transforming foci in fibroblasts. The Mras GTP/GDP cycle was sensitive to the inclusion of Sos1 (182530), Grf1 (606600), and p120 RasGAP (139150). Mras also immunoprecipitated with Af6 (159559). </p><p>By representational difference analysis, Louahed et al. (1999) found that Mras expression was induced by interleukin-9 (IL9; 146931) in a mouse T-helper cell clone. Induction seemed to depend upon the JAK (see 147795)/STAT (see 600555) pathway. In addition, IL3 (147740), but not IL9, increased GTP binding to Mras. A constitutively activated Mras mutant induced activation of Elk transcription factor (see 311040) by triggering the MAPK pathway and allowed IL3-independent proliferation of the mouse pro-B cell line BaF3. </p><p>The MRAS GTPase, SHOC2 (602775), and protein phosphatase-1 (PP1; see 176875) interact to form a heterotrimeric holoenzyme that dephosphorylates the S259 inhibitory site on RAF kinases, activating downstream signaling. Young et al. (2018) showed that MRAS and SHOC2 function as PP1 regulatory subunits, providing the complex with striking specificity against RAF. MRAS also functions as a targeting subunit, as membrane localization is required for efficient RAF dephosphorylation and ERK pathway regulation in cells. </p>
|
|
</span>
|
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<div>
|
|
<br />
|
|
</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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|
|
<span class="mim-text-font">
|
|
<p>Stumpf (2025) mapped the MRAS gene to chromosome 3q22.3 based on an alignment of the MRAS sequence (GenBank BC035939) with the genomic sequence (GRCh38).</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Higgins et al. (2017) reported 2 patients with Noonan syndrome and concomitant cardiac hypertrophy (NS11; 618499) who carried de novo heterozygous missense mutations in the MRAS gene. The first patient carried a gly23-to-val (G23V; 608435.0001) mutation and the second a thr68-to-ile mutation (T68I; 608435.0002). The mutations were identified by whole-exome sequencing and sequencing of the MRAS gene, respectively. The G23V mutation was studied extensively and found to result in a constitutively active form of MRAS. </p><p>Suzuki et al. (2019) reported a patient with a severe Noonan phenotype including hypertrophic cardiomyopathy who was heterozygous for a de novo gln71-to-arg (Q71R; 608435.0003) mutation in MRAS. The authors noted that gln71 is highly conserved from zebrafish to humans, and that gln71 of MRAS corresponds to gln61 of HRAS (190020), KRAS (190070), and NRAS (164790), within the nucleotide-binding switch II region critical for the activation of proteins. </p><p>MRAS, a close relative of RAS oncoproteins, interacts with SHOC2 (602775) and protein phosphatase-1 (PP1; see 176875) to form a heterotrimeric holoenzyme that dephosphorylates an inhibitory site on RAF kinases, activating downstream signaling. Young et al. (2018) showed that the MRAS mutation G23V (equivalent to the oncogenic G13V in classical RAS proteins), like MRAS Q71L (Q61L in RAS), shows increased interaction with other effectors such as BRAF (164757), CRAF (RAF1; 164760), and AF6 (MLLT4; 159559), consistent with activating mutations leading to GTP-loading of MRAS. On the other hand, the T68I mutation, which is located in switch II, did not stimulate binding to BRAF or CRAF. This suggested that, while MRAS G23V can drive RAF activation through both direct binding and complex formation with SHOC2-PP1, the MRAS T68I substitution discriminates between effectors, selecting specifically for interaction with SHOC2 and PP1 and thus the RAF phosphatase function of MRAS. Young et al. (2018) showed that mutations in MRAS, SHOC2, and PPP1CB (600590) that result in Noonan syndrome invariably promote complex formation with each other, but not necessarily with other interactors. Thus, Noonan syndrome in individuals with SHOC2, MRAS, or PPPC1B mutations is likely driven at the biochemical level by enhanced ternary complex formation and highlights the crucial role of this phosphatase holoenzyme in RAF S259 dephosphorylation, ERK pathway dynamics, and normal human development. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>3 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 NOONAN SYNDROME 11</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MRAS, GLY23VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1576359216,
|
|
|
|
|
|
|
|
ClinVar: RCV000787303, RCV003155311, RCV005092354
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 15-year-old girl with Noonan syndrome-11 (NS11; 618499), Higgins et al. (2017) identified a heterozygous c.68G-T transversion (c.68G-T, NM_012219) in the MRAS gene resulting in a glycine-to-valine substitution at codon 23 (G23V). This variant occurred as a de novo event and was not seen in over 280,000 alleles in gnomAD. In silico and structural analyses predicted that this variant would result in constitutive activation of the protein. Biochemical studies showed a 40-fold increase in GTP loading, as well as increased ERK activation and signaling and transcription activation in response to growth factors. </p><p>Young et al. (2018) showed that the MRAS mutation G23V, equivalent to the oncogenic G13V in classical RAS proteins, showed increased interaction with other effectors such as BRAF (164757), CRAF (RAF1; 164760), and AF6 (MLLT4; 159559), consistent with activating mutations leading to GTP-loading of MRAS. </p>
|
|
</span>
|
|
</div>
|
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|
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|
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<div>
|
|
<br />
|
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</div>
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|
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</div>
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|
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|
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 NOONAN SYNDROME 11</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
MRAS, THR68ILE
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|
|
<br />
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|
|
SNP: rs1576387876,
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|
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ClinVar: RCV000787304, RCV002536888, RCV004732489
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|
|
</span>
|
|
</div>
|
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|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 6-year-old girl with Noonan syndrome-11 (NS11; 618499), Higgins et al. (2017) identified a heterozygous c.203C-T transition (c.203C-T, NM_012219) in the MRAS gene resulting in a threonine-to-isoleucine substitution at codon 68 (T68I). This variant occurred as a de novo event and was not seen in gnomAD. In silico analyses predicted that this was a deleterious mutation, but no functional assays were performed. </p>
|
|
</span>
|
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</div>
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<div>
|
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<br />
|
|
</div>
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</div>
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<div>
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 NOONAN SYNDROME 11</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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|
|
|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
MRAS, GLN71ARG
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<br />
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|
|
SNP: rs1576387885,
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|
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ClinVar: RCV000787305
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|
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|
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</span>
|
|
</div>
|
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|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 2-year-old Japanese boy with a severe Noonan syndrome phenotype that included hypertrophic cardiomyopathy (NS11; 618499), Suzuki et al. (2019) detected a heterozygous de novo c.212A-G transition (c.212A-G, NM_001085049.2) in the MRAS gene that resulted in a glutamine-to-arginine substitution at codon 71 (Q71R). This variant was not seen in gnomAD (Hamosh, 2019). The Q71 codon in MRAS corresponds to the Q61 codon in classical RAS proteins, and Suzuki et al. (2019) stated that studies of the Q61R mutation in NRAS (164790.0002) had found a GTP hydrolysis rate that was drastically slower than that of wildtype (Burd et al., 2014). The Q71R mutation occurs in the nucleotide-binding switch II region of MRAS, critical for protein activation. Functional assays were not performed. </p><p>Young et al. (2018) showed that the MRAS mutation Q71L, equivalent to Q61L in classical RAS proteins, shows increased interaction with other effectors such as BRAF (164757), CRAF (RAF1; 164760), and AF6 (MLLT4; 159559), consistent with activating mutations leading to GTP-loading of MRAS. </p>
|
|
</span>
|
|
</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>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Burd, C. E., Liu, W., Huynh, M. V., Waqas, M. A., Gillahan, J. E., Clark, K. S., Fu, K., Martin, B. L., Jeck, W. R., Souroullas, G. P., Darr, D. B., Zedek, D. C., Miley, M. J., Baguley, B. C., Campbell, S. L., Sharpless, N. E.
|
|
<strong>Mutation-specific RAS oncogenicity explains NRAS codon 61 selection in melanoma.</strong>
|
|
Cancer Discov. 4: 1418-1429, 2014.
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|
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|
|
[PubMed: 25252692]
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|
|
[Full Text: https://doi.org/10.1158/2159-8290.CD-14-0729]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hamosh, A.
|
|
<strong>Personal Communication.</strong>
|
|
Baltimore, Md. 07/07/2019.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Higgins, E. M., Bos, J. M., Mason-Suares, H., Tester, D. J., Ackerman, J. P., MacRae, C. A., Sol-Church, K., Gripp, K. W., Urrutia, R., Ackerman, M. J.
|
|
<strong>Elucidation of MRAS-mediated Noonan syndrome with cardiac hypertrophy.</strong>
|
|
JCI Insight 2: e91225, 2017. Note: Electronic Article.
|
|
|
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|
|
[PubMed: 28289718]
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|
|
[Full Text: https://doi.org/10.1172/jci.insight.91225]
|
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kimmelman, A., Tolkacheva, T., Lorenzi, M. V., Osada, M., Chan, A. M.-L.
|
|
<strong>Identification and characterization of R-ras3: a novel member of the RAS gene family with a non-ubiquitous pattern of tissue distribution.</strong>
|
|
Oncogene 15: 2675-2685, 1997.
|
|
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|
|
[PubMed: 9400994]
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|
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|
|
[Full Text: https://doi.org/10.1038/sj.onc.1201674]
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|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Louahed, J., Grasso, L., De Smet, C., Van Roost, E., Wildmann, C., Nicolaides, N. C., Levitt, R. C., Renauld, J.-C.
|
|
<strong>Interleukin-9-induced expression of M-Ras/R-Ras3 oncogene in T-helper clones.</strong>
|
|
Blood 94: 1701-1710, 1999.
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|
|
[PubMed: 10477695]
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</p>
|
|
</li>
|
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|
|
<li>
|
|
<p class="mim-text-font">
|
|
Matsumoto, K., Asano, T., Endo, T.
|
|
<strong>Novel small GTPase M-Ras participates in reorganization of actin cytoskeleton.</strong>
|
|
Oncogene 15: 2409-2417, 1997.
|
|
|
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|
|
[PubMed: 9395237]
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|
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|
|
[Full Text: https://doi.org/10.1038/sj.onc.1201416]
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|
</p>
|
|
</li>
|
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|
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<li>
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Quilliam, L. A., Castro, A. F., Rogers-Graham, K. S., Martin, C. B., Der, C. J., Bi, C.
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<strong>M-Ras/R-Ras3, a transforming Ras protein regulated by Sos1, GRF1, and p120 Ras GTPase-activating protein, interacts with the putative Ras effector AF6.</strong>
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J. Biol. Chem. 274: 23850-23857, 1999.
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[PubMed: 10446149]
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[Full Text: https://doi.org/10.1074/jbc.274.34.23850]
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Stumpf, A. M.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 2/12/2025.
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Suzuki, H., Takenouchi, T., Uehara, T., Takasago, S., Ihara, S., Yoshihashi, H., Kosaki, K.
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<strong>Severe Noonan syndrome phenotype associated with a germline Q71R MRAS variant: a recurrent substitution in RAS homologs in various cancers.</strong>
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Am. J. Med. Genet. 179A: 1628-1630, 2019.
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[PubMed: 31173466]
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[Full Text: https://doi.org/10.1002/ajmg.a.61261]
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<strong>SHOC2-MRAS-PP1 complex positively regulates RAF activity and contributes to Noonan syndrome pathogenesis.</strong>
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Proc. Nat. Acad. Sci. 115: E10576-E10585, 2018. Note: Electronic Article.
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[PubMed: 30348783]
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[Full Text: https://doi.org/10.1073/pnas.1720352115]
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