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Entry
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- *164790 - NRAS PROTOONCOGENE, GTPase; NRAS
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*164790</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="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#geneFunction">Gene Function</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</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/164790">Table View</a>
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<a href="#seeAlso"><strong>See Also</strong></a>
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</li>
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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 class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000213281;t=ENST00000369535" 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=4893" 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=164790" 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 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=ENSG00000213281;t=ENST00000369535" 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_002524" 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_002524" 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=164790" 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=01273&isoform_id=01273_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/NRAS" 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/35092,35103,35891,131883,190927,544857,553633,553638,825697,929658,1335234,1335235,1335236,1335287,4505451,13528840,20147731,37595069,54696334,54696336,119577012,119577013,119577014,119577015,166706797,300599563,576060863,1682104299,1682104301,1682104303,2098512376,2186152458,2186152460,2186152462,2186152464,2186152466,2186152468,2186152471" 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/P01111" 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=4893" 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=ENSG00000213281;t=ENST00000369535" 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=NRAS" 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=NRAS" 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+4893" 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/NRAS" 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:4893" 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/4893" 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=chr1&hgg_gene=ENST00000369535.5&hgg_start=114704469&hgg_end=114716771&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:7989" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/nras" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=164790[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=164790[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/NRAS/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/ENSG00000213281" 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=NRAS" 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=NRAS" 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=NRAS" 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=NRAS&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/PA31768" 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:7989" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0003205.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:97376" 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/NRAS#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:97376" 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/4893/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=4893" 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=WBGene00002335;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-990415-166" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://catalog.coriell.org/Search?q=OmimNum:164790" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:4893" 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=NRAS&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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164790
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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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NRAS PROTOONCOGENE, GTPase; NRAS
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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>
|
|
<span class="mim-font">
|
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NEUROBLASTOMA RAS VIRAL ONCOGENE HOMOLOG<br />
|
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ONCOGENE NRAS; NRAS1
|
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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=NRAS" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">NRAS</a></em></strong>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/1/943?start=-3&limit=10&highlight=943">1p13.2</a>
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr1:114704469-114716771&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'})">1:114,704,469-114,716,771</a> </span>
|
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</em>
|
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
|
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</p>
|
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</div>
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<div>
|
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<br />
|
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</div>
|
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=614470,114500,162900,137550,249400,613224,163200,188470" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
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</span>
|
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|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
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</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="8">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/1/943?start=-3&limit=10&highlight=943">
|
|
1p13.2
|
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</a>
|
|
</span>
|
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</td>
|
|
|
|
|
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<td>
|
|
<span class="mim-font">
|
|
?RAS-associated autoimmune lymphoproliferative syndrome type IV, somatic
|
|
|
|
<span class="mim-tip-hint" title="A question mark (?) indicates that the relationship between the phenotype and gene is provisional">
|
|
<span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span>
|
|
</span>
|
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/614470"> 614470 </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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</span>
|
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</td>
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<td>
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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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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
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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/164790" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/164790" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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</ul>
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</div>
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<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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<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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<p><a href="#24" class="mim-tip-reference" title="Marshall, C. J., Hall, A., Weiss, R. A. <strong>A transforming gene present in human sarcoma cell lines.</strong> Nature 299: 171-173, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6287287/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6287287</a>] [<a href="https://doi.org/10.1038/299171a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6287287">Marshall et al. (1982)</a> identified a gene with transforming activity in 2 different human sarcoma cell lines, a fibrosarcoma (HT1080) and an embryonal rhabdomyosarcoma (RD). <a href="#17" class="mim-tip-reference" title="Hall, A., Marshall, C. J., Spurr, N. K., Weiss, R. A. <strong>Identification of transforming gene in two human sarcoma cell lines as a new member of the ras gene family located on chromosome 1.</strong> Nature 303: 396-400, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6304521/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6304521</a>] [<a href="https://doi.org/10.1038/303396a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6304521">Hall et al. (1983)</a> identified this gene as a member of the RAS gene family and designated it N-RAS 'after consultation with Wigler and with Weinberg.' They found that NRAS was also activated in a promyelocytic leukemia cell line (HL60) and a neuroblastoma cell line (SK-H-SH). NRAS was present at the same levels in normal fibroblasts and tumor cells. <a href="#16" class="mim-tip-reference" title="Hall, A., Brown, R. <strong>Human N-ras: cDNA cloning and gene structure.</strong> Nucleic Acids Res. 13: 5255-5268, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2991860/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2991860</a>] [<a href="https://doi.org/10.1093/nar/13.14.5255" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2991860">Hall and Brown (1985)</a> identified 2 main NRAS transcripts of 4.3 kb and 2 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2991860+6287287+6304521" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>Gene Structure</strong>
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<p><a href="#16" class="mim-tip-reference" title="Hall, A., Brown, R. <strong>Human N-ras: cDNA cloning and gene structure.</strong> Nucleic Acids Res. 13: 5255-5268, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2991860/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2991860</a>] [<a href="https://doi.org/10.1093/nar/13.14.5255" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2991860">Hall and Brown (1985)</a> determined that the NRAS gene contains 7 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2991860" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>Mapping</strong>
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<p>By restriction mapping and Southern blot analysis, <a href="#17" class="mim-tip-reference" title="Hall, A., Marshall, C. J., Spurr, N. K., Weiss, R. A. <strong>Identification of transforming gene in two human sarcoma cell lines as a new member of the ras gene family located on chromosome 1.</strong> Nature 303: 396-400, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6304521/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6304521</a>] [<a href="https://doi.org/10.1038/303396a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6304521">Hall et al. (1983)</a> mapped the NRAS gene to chromosome 1. By in situ hybridization, <a href="#6" class="mim-tip-reference" title="Davis, M., Malcolm, S., Hall, A., Marshall, C. J. <strong>Localisation of the human N-ras oncogene to chromosome 1cen-p21 by in situ hybridisation.</strong> EMBO J. 2: 2281-2283, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6667677/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6667677</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1983.tb01735.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6667677">Davis et al. (1983)</a> assigned the NRAS gene to the short arm of chromosome 1. A concentration of grains was observed just above the centromere in band 1p13. They commented on the wide dispersion of the oncogenes in the RAS family; each of the 5 mapped to date was on a separate chromosome. <a href="#40" class="mim-tip-reference" title="Ryan, J., Barker, P. E., Shimizu, K., Wigler, M., Ruddle, F. H. <strong>Chromosomal assignment of a family of human oncogenes.</strong> Proc. Nat. Acad. Sci. 80: 4460-4463, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6576347/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6576347</a>] [<a href="https://doi.org/10.1073/pnas.80.14.4460" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6576347">Ryan et al. (1983)</a> confirmed assignment of HRAS (<a href="/entry/190020">190020</a>) to chromosome 11, KRAS2 (<a href="/entry/190070">190070</a>) to chromosome 12, and NRAS to chromosome 1. Addendum in proof indicated that the same laboratory had assigned NRAS1 to 1p21-cen. <a href="#9" class="mim-tip-reference" title="de Martinville, B., Cunningham, J. M., Murray, M. J., Francke, U. <strong>The N-ras oncogene assigned to chromosome 1 (p31-cen) by somatic cell hybrid analysis. (Abstract)</strong> Cytogenet. Cell Genet. 37: 531 only, 1984."None>De Martinville et al. (1984)</a> assigned NRAS to 1p31-cen. By somatic cell hybrid studies and by in situ hybridization, <a href="#37" class="mim-tip-reference" title="Rabin, M., Watson, M., Barker, P. E., Ryan, J., Breg, W. R., Ruddle, F. H. <strong>NRAS transforming gene maps to region p11-p13 on chromosome 1 by in situ hybridization.</strong> Cytogenet. Cell Genet. 38: 70-72, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6705568/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6705568</a>] [<a href="https://doi.org/10.1159/000132032" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6705568">Rabin et al. (1984)</a> assigned the NRAS gene to 1p13-p11. By in situ hybridization, <a href="#35" class="mim-tip-reference" title="Popescu, N. C., Amsbaugh, S. C., DiPaolo, J. A., Tronick, S. R., Aaronson, S. A., Swan, D. C. <strong>Chromosomal localization of three human ras genes by in situ molecular hybridization.</strong> Somat. Cell Molec. Genet. 11: 149-155, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3856955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3856955</a>] [<a href="https://doi.org/10.1007/BF01534703" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3856955">Popescu et al. (1985)</a> also assigned the NRAS locus to 1p13-p11. <a href="#36" class="mim-tip-reference" title="Povey, S., Morton, N. E., Sherman, S. L. <strong>Report of the committee on the genetic constitution of chromosomes 1 and 2 (HGM8).</strong> Cytogenet. Cell Genet. 40: 67-106, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3864603/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3864603</a>] [<a href="https://doi.org/10.1159/000132170" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3864603">Povey et al. (1985)</a> reviewed the conflicting evidence on the site of NRAS on 1p. They found evidence favoring both 1p22 and 1p12-p11. <a href="#12" class="mim-tip-reference" title="Dracopoli, N. C., Meisler, M. H. <strong>Mapping the human amylase gene cluster on the proximal short arm of chromosome 1 using a highly informative (CA)n repeat.</strong> Genomics 7: 97-102, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1692298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1692298</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90523-w" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1692298">Dracopoli and Meisler (1990)</a> concluded from linkage analysis and pulsed field gel electrophoresis that TSHB (<a href="/entry/188540">188540</a>), NGFB (<a href="/entry/162030">162030</a>), and NRAS form a tightly linked gene cluster located in the same chromosomal band. Their location proximal to the AMY2B gene in 1p21 and close linkage to the alpha-satellite centromeric repeat D1Z5 provided strong evidence that the correct assignment for these 3 loci is 1p13 and not 1p22. <a href="#28" class="mim-tip-reference" title="Mitchell, E. L. D., Jones, D., White, G. R. M., Varley, J. M., Santibanez Koref, M. F. <strong>Determination of the gene order of the three loci CD2, NGFB, and NRAS at human chromosome band 1p13 and refinement of their localisation at the subband level by fluorescence in situ hybridization.</strong> Cytogenet. Cell Genet. 70: 183-185, 1995. Note: Erratum: Cytogenet Cell Genet. 71: 306 only, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7789166/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7789166</a>] [<a href="https://doi.org/10.1159/000134028" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7789166">Mitchell et al. (1995)</a> localized NRAS to 1p13.2 and CD2 (<a href="/entry/186990">186990</a>) and NGFB to 1p13.1. They concluded that the order is as follows: cen--CD2--NGFB--NRAS--tel. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6667677+1692298+3856955+6576347+3864603+7789166+6705568+6304521" 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 teratomas (see <a href="/entry/166950">166950</a>) as a means of 'centromere mapping,' <a href="#10" class="mim-tip-reference" title="Deka, R., Majumder, P. P., Warren, A. C., Surti, U., Hoffner, L., Hauselman, E., Antonarakis, S. E., Ferrell, R. E., Chakravarti, A. <strong>Gene-centromere mapping using ovarian teratomas: results from chromosomes 1p, 13q and 21q. (Abstract)</strong> Am. J. Hum. Genet. 45 (suppl.): A137 only, 1989."None>Deka et al. (1989)</a> estimated the NRAS-centromere distance (y) to be 0.30.</p>
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<p>Substitution of ser17 with asn (S17N) in any of the RAS proteins produces dominant-inhibitory proteins with higher affinities for exchange factors than normal RAS. These mutants cannot interact with downstream effectors and therefore form unproductive complexes, preventing activation of endogenous RAS. Using experiments in COS-7 cells, mouse fibroblasts, and canine kidney cells, <a href="#25" class="mim-tip-reference" title="Matallanas, D., Arozarena, I., Berciano, M. T., Aaronson, D. S., Pellicer, A., Lafarga, M., Crespo, P. <strong>Differences on the inhibitory specificities of H-Ras, K-Ras, and N-Ras (N17) dominant negative mutants are related to their membrane microlocalization.</strong> J. Biol. Chem. 278: 4572-4581, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12458225/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12458225</a>] [<a href="https://doi.org/10.1074/jbc.M209807200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12458225">Matallanas et al. (2003)</a> found that the Hras, Kras, and Nras S17N mutants exhibited distinct inhibitory effects that appeared to be due largely to their specific membrane localizations. The authors demonstrated that Hras is present in caveolae, lipid rafts, and bulk disordered membranes, whereas Kras and Nras are present primarily in disordered membranes and lipid rafts, respectively. Thus, the Hras S17N mutant inhibited activation of all 3 wildtype RAS isoforms, the Kras S17N mutant inhibited wildtype Kras and the portion of Hras in disordered membranes, and the Nras S17N mutant inhibited wildtype Nras and the portion of Hras in lipid rafts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12458225" 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="#39" class="mim-tip-reference" title="Rocks, O., Peyker, A., Kahms, M., Verveer, P. J., Koerner, C., Lumbierres, M., Kuhlmann, J., Waldmann, H., Wittinghofer, A., Bastiaens, P. I. H. <strong>An acylation cycle regulates localization and activity of palmitoylated Ras isoforms.</strong> Science 307: 1746-1752, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15705808/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15705808</a>] [<a href="https://doi.org/10.1126/science.1105654" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15705808">Rocks et al. (2005)</a> showed that the specific subcellular distribution of HRAS and NRAS guanosine triphosphate-binding proteins is generated by a constitutive de/reacylation cycle that operates on palmitoylated proteins, driving their rapid exchange between the plasma membrane and the Golgi apparatus. Depalmitoylation redistributes farnesylated Ras in all membranes, followed by repalmitoylation and trapping of Ras at the Golgi, from where it is redirected to the plasma membrane via the secretory pathway. This continuous cycle prevents Ras from nonspecific residence on endomembranes, thereby maintaining the specific intracellular compartmentalization. <a href="#39" class="mim-tip-reference" title="Rocks, O., Peyker, A., Kahms, M., Verveer, P. J., Koerner, C., Lumbierres, M., Kuhlmann, J., Waldmann, H., Wittinghofer, A., Bastiaens, P. I. H. <strong>An acylation cycle regulates localization and activity of palmitoylated Ras isoforms.</strong> Science 307: 1746-1752, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15705808/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15705808</a>] [<a href="https://doi.org/10.1126/science.1105654" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15705808">Rocks et al. (2005)</a> found that the de/reacylation cycle also initiates Ras activation at the Golgi by transport of plasma membrane-localized Ras guanosine triphosphate. Different de/repalmitoylation kinetics account for isoform-specific activation responses to growth factors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15705808" 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="#15" class="mim-tip-reference" title="Haigis, K. M., Kendall, K. R., Wang, Y., Cheung, A., Haigis, M. C., Glickman, J. N., Niwa-Kawakita, M., Sweet-Cordero, A., Sebolt-Leopold, J., Shannon, K. M., Settleman, J., Giovannini, M., Jacks, T. <strong>Differential effects of oncogenic K-Ras and N-Ras on proliferation, differentiation and tumor progression in the colon.</strong> Nature Genet. 40: 600-608, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18372904/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18372904</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18372904[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.115" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18372904">Haigis et al. (2008)</a> used genetically engineered mice to determine whether and how the related oncogenes Kras (<a href="/entry/190070">190070</a>) and Nras regulate homeostasis and tumorigenesis in the colon. Expression of Kras(G12D) in the colonic epithelium stimulated hyperproliferation in a Mek (see <a href="/entry/176872">176872</a>)-dependent manner. Nras(G12D) did not alter the growth properties of the epithelium, but was able to confer resistance to apoptosis. In the context of an Apc (<a href="/entry/611731">611731</a>)-mutant colonic tumor, activation of Kras led to defects in terminal differentiation and expansion of putative stem cells within the tumor epithelium. This Kras tumor phenotype was associated with attenuated signaling through the MAPK pathway (see <a href="/entry/176872">176872</a>), and human colon cancer cells expressing mutant Kras were hypersensitive to inhibition of Raf (see <a href="/entry/164760">164760</a>) but not Mek. <a href="#15" class="mim-tip-reference" title="Haigis, K. M., Kendall, K. R., Wang, Y., Cheung, A., Haigis, M. C., Glickman, J. N., Niwa-Kawakita, M., Sweet-Cordero, A., Sebolt-Leopold, J., Shannon, K. M., Settleman, J., Giovannini, M., Jacks, T. <strong>Differential effects of oncogenic K-Ras and N-Ras on proliferation, differentiation and tumor progression in the colon.</strong> Nature Genet. 40: 600-608, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18372904/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18372904</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18372904[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.115" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18372904">Haigis et al. (2008)</a> concluded that their studies demonstrated clear phenotypic differences between mutant Kras and Nras, and suggested that the oncogenic phenotype of mutant Kras might be mediated by noncanonical signaling through Ras effector pathways. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18372904" 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="#30" class="mim-tip-reference" title="Nazarian, R., Shi, H., Wang, Q., Kong, X., Koya, R. C., Lee, H., Chen, Z., Lee, M.-K., Attar, N., Sazegar, H., Chodon, T., Nelson, S. F., McArthur, G., Sosman, J. A., Ribas, A., Lo, R. S. <strong>Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation.</strong> Nature 468: 973-977, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21107323/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21107323</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21107323[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09626" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21107323">Nazarian et al. (2010)</a> showed that acquired resistance of BRAF(V600E) (<a href="/entry/164757#0001">164757.0001</a>)-positive melanomas to PLX4032, a novel class I RAF-selective inhibitor, develops by mutually exclusive PDGFRB (<a href="/entry/173410">173410</a>) upregulation or NRAS mutations but not through secondary mutations in BRAF(V600E). <a href="#30" class="mim-tip-reference" title="Nazarian, R., Shi, H., Wang, Q., Kong, X., Koya, R. C., Lee, H., Chen, Z., Lee, M.-K., Attar, N., Sazegar, H., Chodon, T., Nelson, S. F., McArthur, G., Sosman, J. A., Ribas, A., Lo, R. S. <strong>Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation.</strong> Nature 468: 973-977, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21107323/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21107323</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21107323[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09626" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21107323">Nazarian et al. (2010)</a> used PLX4032-resistant sublines artificially derived from BRAF(V600E)-positive melanoma cell lines and validated key findings in PLX4032-resistant tumors and tumor-matched, short-term cultures from clinical trial patients. Induction of PDGFRB RNA, protein, and tyrosine phosphorylation emerged as a dominant feature of acquired PLX4032 resistance in a subset of melanoma sublines, patient-derived biopsies, and short-term cultures. PDGFRB-upregulated tumor cells had low activated RAS levels and, when treated with PLX4032, did not reactivate the MAPK (see <a href="/entry/176872">176872</a>) pathway significantly. In another subset, high levels of activated NRAS resulting from mutations led to significant MAPK pathway reactivation upon PLX4032 treatment. Knockdown of PDGFRB or NRAS reduced growth of the respective PLX4032-resistant subsets. Overexpression of PDGFRB or mutated NRAS conferred PLX4032 resistance to PLX4032-sensitive parental cell lines. Importantly, <a href="#30" class="mim-tip-reference" title="Nazarian, R., Shi, H., Wang, Q., Kong, X., Koya, R. C., Lee, H., Chen, Z., Lee, M.-K., Attar, N., Sazegar, H., Chodon, T., Nelson, S. F., McArthur, G., Sosman, J. A., Ribas, A., Lo, R. S. <strong>Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation.</strong> Nature 468: 973-977, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21107323/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21107323</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21107323[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09626" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21107323">Nazarian et al. (2010)</a> showed that MAPK reactivation predicts MEK inhibitor sensitivity. Thus, <a href="#30" class="mim-tip-reference" title="Nazarian, R., Shi, H., Wang, Q., Kong, X., Koya, R. C., Lee, H., Chen, Z., Lee, M.-K., Attar, N., Sazegar, H., Chodon, T., Nelson, S. F., McArthur, G., Sosman, J. A., Ribas, A., Lo, R. S. <strong>Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation.</strong> Nature 468: 973-977, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21107323/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21107323</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21107323[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09626" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21107323">Nazarian et al. (2010)</a> concluded that melanomas escape BRAF(V600E) targeting not through secondary BRAF(V600E) mutations but via receptor tyrosine kinase (RTK)-mediated activation of alternative survival pathway(s) or activated RAS-mediated reactivation of the MAPK pathway, suggesting additional therapeutic strategies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21107323" 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 a dual pulse-chase strategy comparing palmitate and protein half-lives in transfected COS-7 cells, followed by inhibitor studies, <a href="#22" class="mim-tip-reference" title="Lin, D. T. S., Conibear, E. <strong>ABHD17 proteins are novel protein depalmitoylases that regulate N-Ras palmitate turnover and subcellular localization.</strong> eLife 4: e11306, 2015. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26701913/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26701913</a>] [<a href="https://doi.org/10.7554/eLife.11306" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26701913">Lin and Conibear (2015)</a> showed that members of the ABHD17 family (see ABHD17A, <a href="/entry/617942">617942</a>) were common targets of depalmitoylation inhibitors and could accelerate palmitate turnover on PSD95 (DLG4; <a href="/entry/602887">602887</a>) and NRAS in COS-7 cells. ABHD17A relocalized depalmitoylated NRAS from plasma membrane to internal cellular membranes in COS-7 cells. Knockdown studies showed that the endogenous ABHD17 proteins redundantly depalmitoylated NRAS in HEK293T cells. <a href="#22" class="mim-tip-reference" title="Lin, D. T. S., Conibear, E. <strong>ABHD17 proteins are novel protein depalmitoylases that regulate N-Ras palmitate turnover and subcellular localization.</strong> eLife 4: e11306, 2015. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26701913/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26701913</a>] [<a href="https://doi.org/10.7554/eLife.11306" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26701913">Lin and Conibear (2015)</a> concluded that ABHD17 proteins regulate NRAS palmitate turnover and subcellular localization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26701913" 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="#43" class="mim-tip-reference" title="Vasko, V., Ferrand, M., Di Cristofaro, J., Carayon, P., Henry, J. F., De Micco, C. <strong>Specific pattern of RAS oncogene mutations in follicular thyroid tumors.</strong> J. Clin. Endocr. Metab. 88: 2745-2752, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12788883/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12788883</a>] [<a href="https://doi.org/10.1210/jc.2002-021186" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12788883">Vasko et al. (2003)</a> performed a pooled analysis of 269 mutations in HRAS, KRAS, and NRAS found in follicular thyroid tumors (FTC; see <a href="/entry/188550">188550</a>) garnered from 39 previous studies. Mutations proved significantly less frequent when detected with than without direct sequencing (12.3% vs 17%). The rates of mutation involving NRAS exon 1 and KRAS exon 2 was less than 1%. Mutations of codon 61 of NRAS were significantly more frequent in follicular tumors (19%) than in papillary cancers (5%) and significantly more frequent in malignant (25%) than in benign (14%) tumors. HRAS mutations in codons 12/13 were found in 2 to 3% of all types of tumors, but HRAS mutations in codon 61 were observed in only 1.4% of tumors, and almost all of them were malignant. KRAS mutations in exon 1 were found more often in papillary than follicular cancers (2.7% vs 1.6%) and were sometimes correlated with special epidemiologic circumstances. The second part of this study involved analysis of 80 follicular tumors from patients living in Marseille (France) and Kiev (Ukraine). HRAS mutations in codons 12/13 were found in 12.5% of common adenomas and 1 follicular carcinoma (2.9%). Mutations of codon 61 of NRAS occurred in 23.3% and 17.6% of atypical adenomas and follicular carcinomas, respectively. The authors concluded that their results confirmed the predominance of mutations of codon 61 of NRAS in thyroid follicular tumors and their correlation with malignancy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12788883" 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="#32" class="mim-tip-reference" title="Nikiforova, M. N., Lynch, R. A., Biddinger, P. W., Alexander, E. K., Dorn, G. W., II, Tallini, G., Kroll, T. G., Nikiforov, Y. E. <strong>RAS point mutations and PAX8-PPAR-gamma rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma.</strong> J. Clin. Endocr. Metab. 88: 2318-2326, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12727991/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12727991</a>] [<a href="https://doi.org/10.1210/jc.2002-021907" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12727991">Nikiforova et al. (2003)</a> analyzed a series of 88 conventional follicular and Hurthle cell thyroid tumors for RAS (HRAS, NRAS, or KRAS) mutations and PAX8 (<a href="/entry/167415">167415</a>)-PPARG (<a href="/entry/601487">601487</a>) rearrangements using molecular methods and for galectin-3 (<a href="/entry/153619">153619</a>) and mesothelioma antibody HBME-1 expression by immunohistochemistry. Forty-nine percent of conventional follicular carcinomas had RAS mutations, 36% had PAX8-PPARG rearrangement, and only 1 (3%) had both. Of follicular adenomas, 48% had RAS mutations, 4% had PAX8-PPARG rearrangement, and 48% had neither. Follicular carcinomas with RAS mutations most often displayed an HBME-1-positive/galectin-3-negative immunophenotype and were either minimally or overtly invasive. Hurthle cell tumors infrequently had PAX8-PPARG rearrangement or RAS mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12727991" 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="#18" class="mim-tip-reference" title="Johnson, S. M., Grosshans, H., Shingara, J., Byrom, M., Jarvis, R., Cheng, A., Labourier, E., Reinert, K. L., Brown, D., Slack, F. J. <strong>RAS is regulated by the let-7 microRNA family.</strong> Cell 120: 635-647, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15766527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15766527</a>] [<a href="https://doi.org/10.1016/j.cell.2005.01.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15766527">Johnson et al. (2005)</a> found that the 3 human RAS genes, HRAS KRAS, and NRAS, contain multiple let-7 (see <a href="/entry/605386">605386</a>) miRNA complementary sites in their 3-prime UTRs that allow let-7 miRNA to regulate their expression. Let-7 expression was lower in lung tumors than in normal lung tissue, whereas expression of the RAS proteins was significantly higher in lung tumors, suggesting a possible mechanism for let-7 in cancer. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15766527" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Role In Hematologic Malignancies</em></strong></p><p>
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Using the allele-specific amplification method (ARMS), a highly sensitive 1-stage allele-specific PCR, <a href="#1" class="mim-tip-reference" title="Bezieau, S., Devilder, M.-C., Avet-Loiseau, H., Mellerin, M.-P., Puthier, D., Pennarun, E., Rapp, M.-J., Harousseau, J.-L., Moisan, J.-P., Bataille, R. <strong>High incidence of N and K-Ras activating mutations in multiple myeloma and primary plasma cell leukemia at diagnosis.</strong> Hum. Mutat. 18: 212-224, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11524732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11524732</a>] [<a href="https://doi.org/10.1002/humu.1177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11524732">Bezieau et al. (2001)</a> evaluated the incidence of NRAS- and KRAS2-activating mutations (in codons 12, 13, and 61) in 62 patients with monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM), or primary plasma cell leukemia (PPCL), and in human myeloma cell lines (HMCL). Mutations in one or the other gene, or in both, were found in 54.5% of MM patients at diagnosis (but in 81% at the time of relapse), 50% of PPCL patients, and 50% of 16 HMCL patients. In contrast, the occurrence of such mutations was very low in MGUS and indolent MM (12.5%). KRAS2 mutations were always more frequent than NRAS mutations. <a href="#1" class="mim-tip-reference" title="Bezieau, S., Devilder, M.-C., Avet-Loiseau, H., Mellerin, M.-P., Puthier, D., Pennarun, E., Rapp, M.-J., Harousseau, J.-L., Moisan, J.-P., Bataille, R. <strong>High incidence of N and K-Ras activating mutations in multiple myeloma and primary plasma cell leukemia at diagnosis.</strong> Hum. Mutat. 18: 212-224, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11524732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11524732</a>] [<a href="https://doi.org/10.1002/humu.1177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11524732">Bezieau et al. (2001)</a> concluded that these early mutations may play a major role in the oncogenesis of multiple myeloid myeloma and primary plasma cell leukemia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11524732" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In white blood cells derived from 8 patients with juvenile myelomonocytic leukemia (JMML; <a href="/entry/607785">607785</a>), <a href="#26" class="mim-tip-reference" title="Matsuda, K., Shimada, A., Yoshida, N., Ogawa, A., Watanabe, A., Yajima, S., Iizuka, S., Koike, K., Yanai, F., Kawasaki, K., Yanagimachi, M., Kikuchi, A., and 10 others. <strong>Spontaneous improvement of hematologic abnormalities in patients having juvenile myelomonocytic leukemia with specific RAS mutations.</strong> Blood 109: 5477-5480, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17332249/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17332249</a>] [<a href="https://doi.org/10.1182/blood-2006-09-046649" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17332249">Matsuda et al. (2007)</a> identified 5 different somatic mutations in the NRAS gene (see, e.g., G12D, <a href="#0007">164790.0007</a> and G13D, <a href="#0003">164790.0003</a>). Each patient carried a single somatic mutation. The patients were ascertained from a cohort of 80 children with JMML. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17332249" 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 <a href="#4" class="mim-tip-reference" title="Cancer Genome Atlas Research Network. <strong>Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia.</strong> New Eng. J. Med. 368: 2059-2074, 2013. Note: Erratum: New Eng. J. Med. 369: 98 only, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23634996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23634996</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23634996[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/10.1056/NEJMoa1301689" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23634996">Cancer Genome Atlas Research Network (2013)</a> analyzed the genomes of 200 clinically annotated adult cases of de novo acute myeloid leukemia (AML; <a href="/entry/601626">601626</a>), using either whole-genome sequencing (50 cases) or whole-exome sequencing (150 cases), along with RNA and microRNA sequencing and DNA methylation analysis. The <a href="#4" class="mim-tip-reference" title="Cancer Genome Atlas Research Network. <strong>Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia.</strong> New Eng. J. Med. 368: 2059-2074, 2013. Note: Erratum: New Eng. J. Med. 369: 98 only, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23634996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23634996</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23634996[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/10.1056/NEJMoa1301689" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23634996">Cancer Genome Atlas Research Network (2013)</a> identified recurrent mutations in the NRAS or KRAS genes in 23 (12%) of 200 samples. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23634996" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Brewin, J., Horne, G., Chevassut, T. <strong>Genomic landscapes and clonality of de novo AML. (Letter)</strong> New Eng. J. Med. 369: 1472-1473, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24106951/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24106951</a>] [<a href="https://doi.org/10.1056/NEJMc1308782" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24106951">Brewin et al. (2013)</a> noted that the study of the <a href="#4" class="mim-tip-reference" title="Cancer Genome Atlas Research Network. <strong>Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia.</strong> New Eng. J. Med. 368: 2059-2074, 2013. Note: Erratum: New Eng. J. Med. 369: 98 only, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23634996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23634996</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23634996[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/10.1056/NEJMoa1301689" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23634996">Cancer Genome Atlas Research Network (2013)</a> did not reveal which mutations occurred in the founding clone, as would be expected for an initiator of disease, and which occurred in minor clones, which subsequently drive disease. <a href="#27" class="mim-tip-reference" title="Miller, C. A., Wilson, R. K., Ley, T. J. <strong>Reply to Brewin et al. (Letter)</strong> New Eng. J. Med. 369: 1473 only, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24106950/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24106950</a>] [<a href="https://doi.org/10.1056/NEJMc1308782" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24106950">Miller et al. (2013)</a> responded that NRAS was among several genes in their study whose mutations were often found in subclones, suggesting that they are often cooperating mutations. The authors also identified other genes that contained mutations they considered probable initiators. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=24106950+24106951+23634996" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>RAS-Associated Autoimmune Leukoproliferative Disorder</em></strong></p><p>
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<a href="#34" class="mim-tip-reference" title="Oliveira, J. B., Bidere, N., Niemela, J. E., Zheng, L., Sakai, K., Nix, C. P., Danner, R. L., Barb, J., Munson, P. J., Puck, J. M., Dale, J., Straus, S. E., Fleisher, T. A., Lenardo, M. J. <strong>NRAS mutation causes a human autoimmune lymphoproliferative syndrome.</strong> Proc. Nat. Acad. Sci. 104: 8953-8958, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17517660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17517660</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17517660[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.0702975104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17517660">Oliveira et al. (2007)</a> identified a heterozygous mutation in the NRAS gene (G13D; <a href="#0003">164790.0003</a>) in a 49-year-old patient with RAS-associated autoimmune leukoproliferative disorder (RALD; <a href="/entry/614470">614470</a>). The patient had a lifelong overexpansion of lymphocytes, childhood leukemia, and early adulthood lymphoma, both successfully treated. He had increased serum CD4-/CD8- alpha/beta T cells and follicular hyperplasia of the lymph nodes. <a href="#31" class="mim-tip-reference" title="Niemela, J. E., Lu, L., Fleisher, T. A., Davis, J., Caminha, I., Natter, M., Beer, L. A., Dowdell, K. C., Pittaluga, S., Raffeld, M., Rao, V. K., Oliveira, J. B. <strong>Somatic KRAS mutations associated with a human nonmalignant syndrome of autoimmunity and abnormal leukocyte homeostasis.</strong> Blood 117: 2883-2886, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21079152/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21079152</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21079152[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/10.1182/blood-2010-07-295501" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21079152">Niemela et al. (2010)</a> stated that the NRAS mutation found by <a href="#34" class="mim-tip-reference" title="Oliveira, J. B., Bidere, N., Niemela, J. E., Zheng, L., Sakai, K., Nix, C. P., Danner, R. L., Barb, J., Munson, P. J., Puck, J. M., Dale, J., Straus, S. E., Fleisher, T. A., Lenardo, M. J. <strong>NRAS mutation causes a human autoimmune lymphoproliferative syndrome.</strong> Proc. Nat. Acad. Sci. 104: 8953-8958, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17517660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17517660</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17517660[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.0702975104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17517660">Oliveira et al. (2007)</a> was a somatic mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21079152+17517660" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Noonan Syndrome 6</em></strong></p><p>
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<a href="#5" class="mim-tip-reference" title="Cirstea, I. C., Kutsche, K., Dvorsky, R., Gremer, L., Carta, C., Horn, D., Roberts, A. E., Lepri, F., Merbitz-Zahradnik, T., Konig, R., Kratz, C. P., Pantaleoni, F., and 19 others. <strong>A restricted spectrum of NRAS mutations cause Noonan syndrome.</strong> Nature. Genet. 42: 27-29, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19966803/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19966803</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19966803[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.497" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19966803">Cirstea et al. (2010)</a> identified 1 of 2 different heterozygous mutations in the NRAS gene (T50I; <a href="#0004">164790.0004</a> and G60E; <a href="#0005">164790.0005</a>) in 5 patients, including a mother and son, with Noonan syndrome-6 (NS6; <a href="/entry/613224">613224</a>). The mutations were de novo in 3 patients. In vitro functional expression studies showed that the mutations resulted in enhanced stimulus-dependent MAPK activation. The patients were part of a larger study of 917 affected individuals who were negative for previously known Noonan-associated gene mutations, suggesting that NRAS mutations are a rare cause of Noonan syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19966803" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Congenital Melanocytic Nevus Syndrome</em></strong></p><p>
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<a href="#11" class="mim-tip-reference" title="Dessars, B., De Raeve, L. E., Morandini, R., Lefort, A., El Housni, H., Ghanem, G. E., Van den Eynde, B. J., Ma, W., Roseeuw, D., Vassart, G., Libert, F., Heimann, P. <strong>Genotypic and gene expression studies in congenital melanocytic nevi: insight into initial steps of melanotumorigenesis.</strong> J. Invest. Derm. 129: 139-147, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18633438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18633438</a>] [<a href="https://doi.org/10.1038/jid.2008.203" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18633438">Dessars et al. (2009)</a> identified a somatic NRAS mutation in samples from 19 (70%) of 27 patients with congenital melanocytic nevi (CMNS; <a href="/entry/137550">137550</a>): 14 nevi carried a Q61K mutation (<a href="#0008">164790.0008</a>), 4 carried a Q61R mutation (<a href="#0002">164790.0002</a>), and 1 carried a G13R mutation (<a href="#0001">164790.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18633438" 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="#19" class="mim-tip-reference" title="Kinsler, V. A., Thomas, A. C., Ishida, M., Bulstrode, N. W., Loughlin, S., Hing, S., Chalker, J., McKenzie, K., Abu-Amero, S., Slater, O., Chanudet, E., Palmer, R., Morrogh, D., Stanier, P., Healy, E., Sebire, N. J., Moore, G. E. <strong>Multiple congenital melanocytic nevi and neurocutaneous melanosis are caused by postzygotic mutations in codon 61 of NRAS.</strong> J. Invest. Derm. 133: 2229-2236, 2013. Note: Erratum: J. Invest. Derm. 136: 2326 only, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23392294/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23392294</a>] [<a href="https://doi.org/10.1038/jid.2013.70" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23392294">Kinsler et al. (2013)</a> identified somatic oncogenic missense mutations affecting codon 61 of the NRAS gene in affected cutaneous and neurologic tissues from 12 of 15 patients with congenital melanocytic nevus syndrome and/or neurocutaneous melanosis (NCMS; <a href="/entry/249400">249400</a>). Affected skin samples from 10 of 13 patients carried a somatic heterozygous mutation, including 8 with Q61K and 2 with Q61R. The same codon 61 mutation was found in each of the anatomically separate melanocytic nevi from the same patient. In addition, all 11 neurologic samples from 5 patients from whom neurologic tissue was available were positive for a somatic Q61K mutation; this included both melanocytic and nonmelanocytic tissue, such as a choroid plexus papilloma and meningioma. In patients with both neurologic and skin samples available, the same mutation was present in both affected tissues. None of the patients carried an NRAS mutation in the blood. Pre- and post-malignant skin tissue was available from a patient with malignant melanoma, which showed a progression from heterozygosity to homozygosity for the Q61K mutation with the onset of malignancy. Mutations at codon 61 in the NRAS gene affect the guanosine triphosphate-binding site and result in constitutive activation of NRAS. <a href="#19" class="mim-tip-reference" title="Kinsler, V. A., Thomas, A. C., Ishida, M., Bulstrode, N. W., Loughlin, S., Hing, S., Chalker, J., McKenzie, K., Abu-Amero, S., Slater, O., Chanudet, E., Palmer, R., Morrogh, D., Stanier, P., Healy, E., Sebire, N. J., Moore, G. E. <strong>Multiple congenital melanocytic nevi and neurocutaneous melanosis are caused by postzygotic mutations in codon 61 of NRAS.</strong> J. Invest. Derm. 133: 2229-2236, 2013. Note: Erratum: J. Invest. Derm. 136: 2326 only, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23392294/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23392294</a>] [<a href="https://doi.org/10.1038/jid.2013.70" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23392294">Kinsler et al. (2013)</a> concluded that multiple congenital melanocytic nevi and neuromelanosis, as well as nonmelanocytic CNS lesions, result from somatic mosaicism, and that the mutation probably occurs in a progenitor cell in the developing neural crest or neuroectoderm. The findings also suggested that these mutations may be lethal in the germline. Three of the original 15 patients with CMNS did not have NRAS mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23392294" 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>Mutations in the RB1 gene (<a href="/entry/614041">614041</a>) predispose humans and mice to tumor development. <a href="#41" class="mim-tip-reference" title="Takahashi, C., Contreras, B., Iwanaga, T., Takegami, Y., Bakker, A., Bronson, R. T., Noda, M., Loda, M., Hunt, J. L., Ewen, M. E. <strong>Nras loss induces metastatic conversion of Rb1-deficient neuroendocrine thyroid tumor.</strong> Nature Genet. 38: 118-123, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16369533/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16369533</a>] [<a href="https://doi.org/10.1038/ng1703" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16369533">Takahashi et al. (2006)</a> assessed the effect of Nras loss on tumor development in Rb1 heterozygous mice. Loss of 1 or 2 Nras alleles significantly reduced the severity of pituitary tumors arising in Rb1 +/- animals by enhancing their differentiation. By contrast, C-cell thyroid adenomas occurring in Rb1 +/- mice progressed to metastatic medullary carcinomas after loss of Nras. In Rb1/Nras doubly heterozygous mice, distant medullary thyroid carcinoma metastases were associated with loss of the remaining wildtype Nras allele. Loss of Nras in Rb1-deficient C cells resulted in elevated Ras homolog family A (RhoA) activity, and this was causally linked to the invasiveness and metastatic behavior of these cells. These findings suggested that the loss of the protooncogene Nras in certain cellular contexts can promote malignant tumor progression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16369533" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>8 Selected Examples</a>):</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=164790[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">rs121434595 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434595;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=rs121434595" 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=rs121434595" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p><a href="#33" class="mim-tip-reference" title="Nitta, N., Ochiai, M., Nagao, M., Sugimura, T. <strong>Amino-acid substitution at codon 13 of the N-ras oncogene in rectal cancer in a Japanese patient.</strong> Jpn. J. Cancer Res. 78: 21-26, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3102434/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3102434</a>]" pmid="3102434">Nitta et al. (1987)</a> found a G-to-C point mutation at the first letter of codon 13 in the NRAS gene as the presumed basis for activation of the gene in a case of rectal cancer (see <a href="/entry/114500">114500</a>). The point mutation resulted in the substitution of arginine for glycine. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3102434" 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="#11" class="mim-tip-reference" title="Dessars, B., De Raeve, L. E., Morandini, R., Lefort, A., El Housni, H., Ghanem, G. E., Van den Eynde, B. J., Ma, W., Roseeuw, D., Vassart, G., Libert, F., Heimann, P. <strong>Genotypic and gene expression studies in congenital melanocytic nevi: insight into initial steps of melanotumorigenesis.</strong> J. Invest. Derm. 129: 139-147, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18633438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18633438</a>] [<a href="https://doi.org/10.1038/jid.2008.203" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18633438">Dessars et al. (2009)</a> identified a heterozygous somatic G13R mutation in 1 of 27 congenital melanocytic nevi (<a href="/entry/137550">137550</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18633438" 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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EPIDERMAL NEVUS, SOMATIC, INCLUDED<br />
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NEUROCUTANEOUS MELANOSIS, SOMATIC, INCLUDED<br />
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SCHIMMELPENNING-FEUERSTEIN-MIMS SYNDROME, SOMATIC MOSAIC, INCLUDED
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NRAS, GLN61ARG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs11554290 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs11554290;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=rs11554290" 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=rs11554290" 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=RCV000014914 OR RCV000032847 OR RCV000037574 OR RCV000114744 OR RCV000114745 OR RCV000148032 OR RCV000413804 OR RCV003992155 OR RCV004668730" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000014914, RCV000032847, RCV000037574, RCV000114744, RCV000114745, RCV000148032, RCV000413804, RCV003992155, RCV004668730" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000014914...</a>
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<p><a href="#32" class="mim-tip-reference" title="Nikiforova, M. N., Lynch, R. A., Biddinger, P. W., Alexander, E. K., Dorn, G. W., II, Tallini, G., Kroll, T. G., Nikiforov, Y. E. <strong>RAS point mutations and PAX8-PPAR-gamma rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma.</strong> J. Clin. Endocr. Metab. 88: 2318-2326, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12727991/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12727991</a>] [<a href="https://doi.org/10.1210/jc.2002-021907" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12727991">Nikiforova et al. (2003)</a> found that the CAA-CGA mutation of NRAS codon 61, resulting in a gln-to-arg change (Q61R), was present in 70% (12) of follicular carcinomas (see <a href="/entry/188550">188550</a>) and 55% (6) of follicular adenomas studied. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12727991" 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="#14" class="mim-tip-reference" title="Hafner, C., Toll, A., Gantner, S., Mauerer, A., Lurkin, I., Acquadro, F., Fernandez-Casado, A., Zwarthoff, E. C., Dietmaier, W., Baselga, E., Parera, E., Vicente, A., Casanova, A., Cigudosa, J., Mentzel, T., Pujol, R. M., Landthaler, M., Real, F. X. <strong>Keratinocytic epidermal nevi are associated with mosaic RAS mutations.</strong> J. Med. Genet. 49: 249-253, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22499344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22499344</a>] [<a href="https://doi.org/10.1136/jmedgenet-2011-100637" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22499344">Hafner et al. (2012)</a> identified a somatic Q61R mutation in 1 of 72 keratinocytic epidermal nevi (<a href="/entry/162900">162900</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22499344" 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="#11" class="mim-tip-reference" title="Dessars, B., De Raeve, L. E., Morandini, R., Lefort, A., El Housni, H., Ghanem, G. E., Van den Eynde, B. J., Ma, W., Roseeuw, D., Vassart, G., Libert, F., Heimann, P. <strong>Genotypic and gene expression studies in congenital melanocytic nevi: insight into initial steps of melanotumorigenesis.</strong> J. Invest. Derm. 129: 139-147, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18633438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18633438</a>] [<a href="https://doi.org/10.1038/jid.2008.203" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18633438">Dessars et al. (2009)</a> identified a somatic Q61R mutation in 4 of 27 congenital melanocytic nevi (<a href="/entry/137550">137550</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18633438" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected skin samples from 2 of 13 patients with congenital melanocytic nevus syndrome (CMNS; <a href="/entry/137550">137550</a>), <a href="#19" class="mim-tip-reference" title="Kinsler, V. A., Thomas, A. C., Ishida, M., Bulstrode, N. W., Loughlin, S., Hing, S., Chalker, J., McKenzie, K., Abu-Amero, S., Slater, O., Chanudet, E., Palmer, R., Morrogh, D., Stanier, P., Healy, E., Sebire, N. J., Moore, G. E. <strong>Multiple congenital melanocytic nevi and neurocutaneous melanosis are caused by postzygotic mutations in codon 61 of NRAS.</strong> J. Invest. Derm. 133: 2229-2236, 2013. Note: Erratum: J. Invest. Derm. 136: 2326 only, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23392294/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23392294</a>] [<a href="https://doi.org/10.1038/jid.2013.70" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23392294">Kinsler et al. (2013)</a> identified a somatic heterozygous c.182C-A transversion in the NRAS gene, resulting in the Q61R mutation. The substitution occurred in the guanosine triphosphate-binding site and was predicted to result in constitutive activation of NRAS. One of the samples from 1 of the patients showed homozygosity for the Q61R mutation: this patient later developed fatal leptomeningeal melanocytic disease (NCMS; <a href="/entry/249400">249400</a>) that was indistinguishable from malignant melanoma. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23392294" 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="#21" class="mim-tip-reference" title="Lim, Y. H., Ovejero, D., Sugarman, J. S., DeKlotz, C. M. C., Maruri, A., Eichenfield, L. F., Kelley, P. K., Juppner, H., Gottschalk, M., Tifft, C. J., Gafni, R. I., Boyce, A. M., and 12 others. <strong>Multilineage somatic activating mutations in HRAS and NRAS cause mosaic cutaneous and skeletal lesions, elevated FGF23 and hypophosphatemia.</strong> Hum. Molec. Genet. 23: 397-407, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24006476/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24006476</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24006476[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/10.1093/hmg/ddt429" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24006476">Lim et al. (2014)</a> identified a Caucasian female who presented at birth with linear epidermal nevi (SFM; <a href="/entry/163200">163200</a>) restricted to the left side of her body and distributed from neck to calf. Histopathology showed acanthosis and papillomatosis. A femur radiograph taken when the patient was 7 years of age revealed dysplastic bone with a sclerotic appearance. At a younger age, she had lesions that were more lytic in nature. In a second patient with this mutation who had congenital melanocytic nevus syndrome (<a href="/entry/137550">137550</a>), <a href="#21" class="mim-tip-reference" title="Lim, Y. H., Ovejero, D., Sugarman, J. S., DeKlotz, C. M. C., Maruri, A., Eichenfield, L. F., Kelley, P. K., Juppner, H., Gottschalk, M., Tifft, C. J., Gafni, R. I., Boyce, A. M., and 12 others. <strong>Multilineage somatic activating mutations in HRAS and NRAS cause mosaic cutaneous and skeletal lesions, elevated FGF23 and hypophosphatemia.</strong> Hum. Molec. Genet. 23: 397-407, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24006476/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24006476</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24006476[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/10.1093/hmg/ddt429" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24006476">Lim et al. (2014)</a> showed that elevated serum FGF23 (<a href="/entry/605380">605380</a>) originated from dysplastic bone with the Q61R mutation. The mutation was absent from normal bone. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24006476" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 JUVENILE MYELOMONOCYTIC LEUKEMIA, SOMATIC</strong>
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RAS-ASSOCIATED AUTOIMMUNE LEUKOPROLIFERATIVE DISORDER, SOMATIC (1 patient), INCLUDED<br />
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NOONAN SYNDROME 6, INCLUDED
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121434596 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434596;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121434596?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121434596" 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=rs121434596" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In white blood cells derived from 2 unrelated children with juvenile myelomonocytic leukemia (JMML; <a href="/entry/607785">607785</a>), <a href="#26" class="mim-tip-reference" title="Matsuda, K., Shimada, A., Yoshida, N., Ogawa, A., Watanabe, A., Yajima, S., Iizuka, S., Koike, K., Yanai, F., Kawasaki, K., Yanagimachi, M., Kikuchi, A., and 10 others. <strong>Spontaneous improvement of hematologic abnormalities in patients having juvenile myelomonocytic leukemia with specific RAS mutations.</strong> Blood 109: 5477-5480, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17332249/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17332249</a>] [<a href="https://doi.org/10.1182/blood-2006-09-046649" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17332249">Matsuda et al. (2007)</a> identified a somatic heterozygous G-to-A transition in the NRAS gene, resulting in a gly13-to-asp (G13D) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17332249" 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="#34" class="mim-tip-reference" title="Oliveira, J. B., Bidere, N., Niemela, J. E., Zheng, L., Sakai, K., Nix, C. P., Danner, R. L., Barb, J., Munson, P. J., Puck, J. M., Dale, J., Straus, S. E., Fleisher, T. A., Lenardo, M. J. <strong>NRAS mutation causes a human autoimmune lymphoproliferative syndrome.</strong> Proc. Nat. Acad. Sci. 104: 8953-8958, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17517660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17517660</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17517660[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.0702975104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17517660">Oliveira et al. (2007)</a> identified a heterozygous G-to-A transition in the NRAS gene, resulting in a gly13-to-asp (G13D) substitution, in a 49-year-old patient with RAS-associated autoimmune leukoproliferative disorder (RALD; <a href="/entry/614470">614470</a>). The patient had a lifelong overexpansion of lymphocytes and a history of childhood leukemia, and early adulthood lymphoma, both successfully treated. There were no developmental defects. Laboratory studies showed increased serum alpha/beta CD4-/CD8- T cells and lymph node follicular hyperplasia. There was no evidence of CD95 (<a href="/entry/134637">134637</a>)-mediated apoptosis, but the patient's lymphocytes resisted death by IL2 (<a href="/entry/147680">147680</a>) withdrawal, indicating a specific defect in lymphocyte apoptosis. Further studies of the patient's cells indicated a decrease of the proapoptotic protein BIM (BCL2L11; <a href="/entry/603827">603827</a>), which is critical for withdrawal-induced mitochondrial apoptosis. The mutation was found in the patient's lymphoblasts, peripheral blood mononuclear cells, monocytes, EBV-transformed B cells, and buccal epithelial cells. It was not present in the patient's unaffected relatives, suggesting de novo occurrence. The patient had no developmental abnormalities or features of Noonan syndrome. <a href="#34" class="mim-tip-reference" title="Oliveira, J. B., Bidere, N., Niemela, J. E., Zheng, L., Sakai, K., Nix, C. P., Danner, R. L., Barb, J., Munson, P. J., Puck, J. M., Dale, J., Straus, S. E., Fleisher, T. A., Lenardo, M. J. <strong>NRAS mutation causes a human autoimmune lymphoproliferative syndrome.</strong> Proc. Nat. Acad. Sci. 104: 8953-8958, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17517660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17517660</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17517660[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.0702975104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17517660">Oliveira et al. (2007)</a> noted that the same mutation had been identified somatically in myeloid and lymphoid malignancies (<a href="#2" class="mim-tip-reference" title="Bos, J. L., Toksoz, D., Marshall, C. J., Verlaan-de Vries, M., Veeneman, G. H., van der Eb, A. J., van Boom, J. H., Janssen, J. W. G., Steenvoorden, A. C. M. <strong>Amino-acid substitutions at codon 13 of the N-ras oncogene in human acute myeloid leukaemia.</strong> Nature 315: 726-730, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2989702/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2989702</a>] [<a href="https://doi.org/10.1038/315726a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2989702">Bos et al., 1985</a>; <a href="#23" class="mim-tip-reference" title="Lubbert, M., Mirro, J., Jr., Miller, C. W., Kahan, J., Isaac, G., Kitchingman, G., Mertelsmann, R., Herrmann, F., McCormick, F., Koeffler, H. P. <strong>N-ras gene point mutations in childhood acute lymphocytic leukemia correlate with a poor prognosis.</strong> Blood 75: 1163-1169, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2407301/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2407301</a>]" pmid="2407301">Lubbert et al., 1990</a>). <a href="#31" class="mim-tip-reference" title="Niemela, J. E., Lu, L., Fleisher, T. A., Davis, J., Caminha, I., Natter, M., Beer, L. A., Dowdell, K. C., Pittaluga, S., Raffeld, M., Rao, V. K., Oliveira, J. B. <strong>Somatic KRAS mutations associated with a human nonmalignant syndrome of autoimmunity and abnormal leukocyte homeostasis.</strong> Blood 117: 2883-2886, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21079152/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21079152</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21079152[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/10.1182/blood-2010-07-295501" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21079152">Niemela et al. (2010)</a> stated that the NRAS mutation found by <a href="#34" class="mim-tip-reference" title="Oliveira, J. B., Bidere, N., Niemela, J. E., Zheng, L., Sakai, K., Nix, C. P., Danner, R. L., Barb, J., Munson, P. J., Puck, J. M., Dale, J., Straus, S. E., Fleisher, T. A., Lenardo, M. J. <strong>NRAS mutation causes a human autoimmune lymphoproliferative syndrome.</strong> Proc. Nat. Acad. Sci. 104: 8953-8958, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17517660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17517660</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17517660[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.0702975104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17517660">Oliveira et al. (2007)</a> was a somatic mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21079152+2989702+17517660+2407301" 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="#8" class="mim-tip-reference" title="De Filippi, P., Zecca, M., Lisini, D., Rosti, V., Cagioni, C., Carlo-Stella, C., Radi, O., Veggiotti, P., Mastronuzzi, A., Acquaviva, A., D'Ambrosio, A., Locatelli, F., Danesino, C. <strong>Germ-line mutation of the NRAS gene may be responsible for the development of juvenile myelomonocytic leukaemia.</strong> Brit. J. Haemat. 147: 706-709, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19775298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19775298</a>] [<a href="https://doi.org/10.1111/j.1365-2141.2009.07894.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19775298">De Filippi et al. (2009)</a> identified a de novo germline heterozygous G13D substitution in the NRAS gene in a male infant who presented at age 2 months with juvenile myelomonocytic leukemia (JMML; <a href="/entry/607785">607785</a>) and was later noted to have dysmorphic features suggestive of, but not diagnostic of, Noonan syndrome (NS6; <a href="/entry/613224">613224</a>). Features included short stature, relative macrocephaly, high forehead, epicanthal folds, long eyebrows, low nasal bridge, low-set ears, 2 cafe-au-lait spots, and low scores on performance tasks. Cardiac studies were normal. There were no hematologic abnormalities related to RALD in this patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19775298" 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">rs267606921 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606921;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=rs267606921" 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=rs267606921" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 2 unrelated boys with Noonan syndrome-6 (NS6; <a href="/entry/613224">613224</a>), <a href="#5" class="mim-tip-reference" title="Cirstea, I. C., Kutsche, K., Dvorsky, R., Gremer, L., Carta, C., Horn, D., Roberts, A. E., Lepri, F., Merbitz-Zahradnik, T., Konig, R., Kratz, C. P., Pantaleoni, F., and 19 others. <strong>A restricted spectrum of NRAS mutations cause Noonan syndrome.</strong> Nature. Genet. 42: 27-29, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19966803/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19966803</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19966803[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.497" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19966803">Cirstea et al. (2010)</a> identified a de novo heterozygous 149C-T transition in exon 3 of the NRAS gene, resulting in a thr50-to-ile (T50I) substitution in a conserved residue located in the beta-2-beta-3 loop connecting the 2 switch regions. In vitro functional expression studies showed that the mutant protein resulted in enhanced downstream phosphorylation in the presence of serum, but did not substantially affect intrinsic GTPase activity. Molecular modeling indicated that thr50 interacts with the polar heads of membrane phospholipids and is an integral part of a region that controls RAS membrane orientation. <a href="#5" class="mim-tip-reference" title="Cirstea, I. C., Kutsche, K., Dvorsky, R., Gremer, L., Carta, C., Horn, D., Roberts, A. E., Lepri, F., Merbitz-Zahradnik, T., Konig, R., Kratz, C. P., Pantaleoni, F., and 19 others. <strong>A restricted spectrum of NRAS mutations cause Noonan syndrome.</strong> Nature. Genet. 42: 27-29, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19966803/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19966803</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19966803[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.497" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19966803">Cirstea et al. (2010)</a> hypothesized that the T50I substitution might alter RAS orientation, increase the interaction of GTP-bound RAS with its effectors, and enhance a downstream signal flow consistent with a gain of function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19966803" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs267606920 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606920;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs267606920?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs267606920" 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=rs267606920" 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=RCV000014917 OR RCV000158982 OR RCV000208552 OR RCV001382056 OR RCV003415702 OR RCV004984642" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000014917, RCV000158982, RCV000208552, RCV001382056, RCV003415702, RCV004984642" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000014917...</a>
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<p>In 3 patients from 2 unrelated families with Noonan syndrome-6 (NS6; <a href="/entry/613224">613224</a>), <a href="#5" class="mim-tip-reference" title="Cirstea, I. C., Kutsche, K., Dvorsky, R., Gremer, L., Carta, C., Horn, D., Roberts, A. E., Lepri, F., Merbitz-Zahradnik, T., Konig, R., Kratz, C. P., Pantaleoni, F., and 19 others. <strong>A restricted spectrum of NRAS mutations cause Noonan syndrome.</strong> Nature. Genet. 42: 27-29, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19966803/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19966803</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19966803[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.497" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19966803">Cirstea et al. (2010)</a> identified a heterozygous 179G-A transition in exon 3 of the NRAS gene, resulting in a gly60-to-glu (G60E) substitution in a conserved residue in the switch 2 region. One proband had a de novo mutation, whereas the other inherited it from his affected mother. In vitro functional expression studies showed that the mutant protein resulted in enhanced downstream phosphorylation in the presence of serum, and that the G60E mutant NRAS protein accumulated constitutively in the active GTP-bound form, although it appeared to be resistant to GAP stimulation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19966803" 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 targeted next-generation sequencing in a father and daughter with Noonan syndrome, <a href="#13" class="mim-tip-reference" title="Ekvall, S., Wilbe, M., Dahlgren, J., Legius, E., van Haeringen, A., Westphal, O., Anneren, G., Bondeson, M.-L. <strong>Mutation in NRAS in familial Noonan syndrome: case report and review of the literature.</strong> BMC Med. Genet. 16: 95, 2015. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26467218/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26467218</a>] [<a href="https://doi.org/10.1186/s12881-015-0239-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26467218">Ekvall et al. (2015)</a> identified heterozygosity for the G60E mutation in the NRAS gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26467218" 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">rs397514553 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397514553;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=rs397514553" 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=rs397514553" 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=RCV000032848 OR RCV000208568" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032848, RCV000208568" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032848...</a>
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<p><a href="#14" class="mim-tip-reference" title="Hafner, C., Toll, A., Gantner, S., Mauerer, A., Lurkin, I., Acquadro, F., Fernandez-Casado, A., Zwarthoff, E. C., Dietmaier, W., Baselga, E., Parera, E., Vicente, A., Casanova, A., Cigudosa, J., Mentzel, T., Pujol, R. M., Landthaler, M., Real, F. X. <strong>Keratinocytic epidermal nevi are associated with mosaic RAS mutations.</strong> J. Med. Genet. 49: 249-253, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22499344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22499344</a>] [<a href="https://doi.org/10.1136/jmedgenet-2011-100637" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22499344">Hafner et al. (2012)</a> identified a somatic pro34-to-leu (P34L) mutation in the NRAS gene in 1 of 72 keratinocytic epidermal nevi (<a href="/entry/162900">162900</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22499344" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121913237 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913237;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121913237?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121913237" 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=rs121913237" 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=RCV000032849 OR RCV000144963 OR RCV000158980 OR RCV001781333 OR RCV001813214 OR RCV001852659 OR RCV003221788 OR RCV003415756 OR RCV004018703" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032849, RCV000144963, RCV000158980, RCV001781333, RCV001813214, RCV001852659, RCV003221788, RCV003415756, RCV004018703" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032849...</a>
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<p><a href="#14" class="mim-tip-reference" title="Hafner, C., Toll, A., Gantner, S., Mauerer, A., Lurkin, I., Acquadro, F., Fernandez-Casado, A., Zwarthoff, E. C., Dietmaier, W., Baselga, E., Parera, E., Vicente, A., Casanova, A., Cigudosa, J., Mentzel, T., Pujol, R. M., Landthaler, M., Real, F. X. <strong>Keratinocytic epidermal nevi are associated with mosaic RAS mutations.</strong> J. Med. Genet. 49: 249-253, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22499344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22499344</a>] [<a href="https://doi.org/10.1136/jmedgenet-2011-100637" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22499344">Hafner et al. (2012)</a> identified a somatic gly12-to-asp (G12D) mutation in the NRAS gene in 1 of 72 keratinocytic epidermal nevi (<a href="/entry/162900">162900</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22499344" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In white blood cells derived from 2 unrelated children with juvenile myelomonocytic leukemia (JMML; <a href="/entry/607785">607785</a>), <a href="#26" class="mim-tip-reference" title="Matsuda, K., Shimada, A., Yoshida, N., Ogawa, A., Watanabe, A., Yajima, S., Iizuka, S., Koike, K., Yanai, F., Kawasaki, K., Yanagimachi, M., Kikuchi, A., and 10 others. <strong>Spontaneous improvement of hematologic abnormalities in patients having juvenile myelomonocytic leukemia with specific RAS mutations.</strong> Blood 109: 5477-5480, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17332249/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17332249</a>] [<a href="https://doi.org/10.1182/blood-2006-09-046649" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17332249">Matsuda et al. (2007)</a> identified a somatic heterozygous G-to-A transition in the NRAS gene, resulting in a gly12-to-asp (G12D) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17332249" 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="#20" class="mim-tip-reference" title="Li, Q., Bohin, N., Wen, T., Ng, V., Magee, J., Chen, S.-C., Shannon, K., Morrison, S. J. <strong>Oncogenic Nras has bimodal effects on stem cells that sustainably increase competitiveness.</strong> Nature 504: 143-147, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24284627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24284627</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24284627[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature12830" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24284627">Li et al. (2013)</a> showed that a single allele of oncogenic Nras(G12D) increases hematopoietic stem cell (HSC) proliferation and also increases reconstituting and self-renewal potential upon serial transplantation in irradiated mice, all prior to leukemia initiation. Nras(G12D) also confers long-term self-renewal potential to multipotent progenitors. <a href="#20" class="mim-tip-reference" title="Li, Q., Bohin, N., Wen, T., Ng, V., Magee, J., Chen, S.-C., Shannon, K., Morrison, S. J. <strong>Oncogenic Nras has bimodal effects on stem cells that sustainably increase competitiveness.</strong> Nature 504: 143-147, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24284627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24284627</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24284627[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature12830" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24284627">Li et al. (2013)</a> found that Nras(G12D) had a bimodal effect on HSCs, increasing the frequency with which some HSCs divide and reducing the frequency with which others divide. This mirrored bimodal effects on reconstituting potential, as rarely dividing Nras(G12D) HSCs outcompeted wildtype HSCs, whereas frequently dividing Nras(G12D) HSCs did not. Nras(G12D) caused these effects by promoting STAT5 (<a href="/entry/601511">601511</a>) signaling, inducing different transcriptional responses in different subsets of HSCs. <a href="#20" class="mim-tip-reference" title="Li, Q., Bohin, N., Wen, T., Ng, V., Magee, J., Chen, S.-C., Shannon, K., Morrison, S. J. <strong>Oncogenic Nras has bimodal effects on stem cells that sustainably increase competitiveness.</strong> Nature 504: 143-147, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24284627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24284627</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24284627[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature12830" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24284627">Li et al. (2013)</a> concluded that 1 signal can therefore increase HSC proliferation, competitiveness, and self-renewal through bimodal effects on HSC gene expression, cycling, and reconstituting potential. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24284627" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0008 MELANOCYTIC NEVUS SYNDROME, CONGENITAL, SOMATIC</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121913254 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913254;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121913254?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121913254" 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=rs121913254" 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=RCV000114746 OR RCV000144964 OR RCV000626456 OR RCV000662267 OR RCV000696329 OR RCV001092890 OR RCV004668769" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000114746, RCV000144964, RCV000626456, RCV000662267, RCV000696329, RCV001092890, RCV004668769" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000114746...</a>
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<p><a href="#11" class="mim-tip-reference" title="Dessars, B., De Raeve, L. E., Morandini, R., Lefort, A., El Housni, H., Ghanem, G. E., Van den Eynde, B. J., Ma, W., Roseeuw, D., Vassart, G., Libert, F., Heimann, P. <strong>Genotypic and gene expression studies in congenital melanocytic nevi: insight into initial steps of melanotumorigenesis.</strong> J. Invest. Derm. 129: 139-147, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18633438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18633438</a>] [<a href="https://doi.org/10.1038/jid.2008.203" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18633438">Dessars et al. (2009)</a> identified a somatic gln61-to-lys (Q61K) mutation in the NRAS gene in 14 of 27 congenital melanocytic nevi (<a href="/entry/137550">137550</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18633438" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected skin samples from 8 of 13 patients with congenital melanocytic nevus syndrome (CMNS; <a href="/entry/137550">137550</a>), including 4 with neurocutaneous melanosis (NCMS; <a href="/entry/249400">249400</a>), <a href="#19" class="mim-tip-reference" title="Kinsler, V. A., Thomas, A. C., Ishida, M., Bulstrode, N. W., Loughlin, S., Hing, S., Chalker, J., McKenzie, K., Abu-Amero, S., Slater, O., Chanudet, E., Palmer, R., Morrogh, D., Stanier, P., Healy, E., Sebire, N. J., Moore, G. E. <strong>Multiple congenital melanocytic nevi and neurocutaneous melanosis are caused by postzygotic mutations in codon 61 of NRAS.</strong> J. Invest. Derm. 133: 2229-2236, 2013. Note: Erratum: J. Invest. Derm. 136: 2326 only, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23392294/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23392294</a>] [<a href="https://doi.org/10.1038/jid.2013.70" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23392294">Kinsler et al. (2013)</a> identified a somatic heterozygous c.181C-A transversion in the NRAS gene, resulting in a gln61-to-lys (Q61K) substitution in the guanosine triphosphate-binding domain. The mutation was predicted to result in constitutive activation of NRAS. Neurologic samples from 5 patients from whom tissue was available were positive for a somatic Q61K mutation, and the same mutation was present in both neurologic and skin samples when available. <a href="#19" class="mim-tip-reference" title="Kinsler, V. A., Thomas, A. C., Ishida, M., Bulstrode, N. W., Loughlin, S., Hing, S., Chalker, J., McKenzie, K., Abu-Amero, S., Slater, O., Chanudet, E., Palmer, R., Morrogh, D., Stanier, P., Healy, E., Sebire, N. J., Moore, G. E. <strong>Multiple congenital melanocytic nevi and neurocutaneous melanosis are caused by postzygotic mutations in codon 61 of NRAS.</strong> J. Invest. Derm. 133: 2229-2236, 2013. Note: Erratum: J. Invest. Derm. 136: 2326 only, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23392294/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23392294</a>] [<a href="https://doi.org/10.1038/jid.2013.70" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23392294">Kinsler et al. (2013)</a> concluded that multiple congenital melanocytic nevi and neuromelanosis, as well as associated nonmelanocytic CNS lesions, result from somatic mosaicism, and that the mutation probably occurs in a progenitor cell in the developing neural crest or neuroectoderm. The findings also suggested that the mutation may be lethal in the germline. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23392294" 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="#Davis1984" class="mim-tip-reference" title="Davis, M., Malcolm, S., Hall, A. <strong>The N-ras oncogene is located on the short arm of chromosome 1. (Abstract)</strong> Cytogenet. Cell Genet. 37: 448-449, 1984.">Davis et al. (1984)</a>; <a href="#Munke1984" class="mim-tip-reference" title="Munke, M., Lindgren, V., de Martinville, B., Francke, U. <strong>Comparative analysis of mouse-human hybrids with rearranged chromosomes 1 by in situ hybridization and Southern blotting: high-resolution mapping of NRAS, NGFB, and AMY on human chromosome 1.</strong> Somat. Cell Molec. Genet. 10: 589-599, 1984.">Munke et al. (1984)</a>; <a href="#Rabin1983" class="mim-tip-reference" title="Rabin, M., Watson, M., Barker, P., Ryan, J., Breg, W. R., Ruddle, F. H. <strong>Chromosomal assignment of human c-fos and N-ras oncogenes. (Abstract)</strong> Am. J. Hum. Genet. 35: 148A only, 1983.">Rabin et al. (1983)</a>; <a href="#Taparowsky1983" class="mim-tip-reference" title="Taparowsky, E., Shimizu, K., Goldfarb, M., Wigler, M. <strong>Structure and activation of the human N-ras gene.</strong> Cell 34: 581-586, 1983.">Taparowsky et al. (1983)</a>; <a href="#Yuasa1984" class="mim-tip-reference" title="Yuasa, Y., Gol, R. A., Chang, A., Chiu, I.-M., Reddy, E. P., Tronick, S. R., Aaronson, S. A. <strong>Mechanism of activation of an N-ras oncogene of SW-1271 human lung carcinoma cells.</strong> Proc. Nat. Acad. Sci. 81: 3670-3674, 1984.">Yuasa et al. (1984)</a>
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<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
|
|
<ol>
|
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<li>
|
|
<a id="1" class="mim-anchor"></a>
|
|
<a id="Bezieau2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bezieau, S., Devilder, M.-C., Avet-Loiseau, H., Mellerin, M.-P., Puthier, D., Pennarun, E., Rapp, M.-J., Harousseau, J.-L., Moisan, J.-P., Bataille, R.
|
|
<strong>High incidence of N and K-Ras activating mutations in multiple myeloma and primary plasma cell leukemia at diagnosis.</strong>
|
|
Hum. Mutat. 18: 212-224, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11524732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11524732</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11524732" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
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[<a href="https://doi.org/10.1002/humu.1177" target="_blank">Full Text</a>]
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|
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</p>
|
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</div>
|
|
</li>
|
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|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Bos1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bos, J. L., Toksoz, D., Marshall, C. J., Verlaan-de Vries, M., Veeneman, G. H., van der Eb, A. J., van Boom, J. H., Janssen, J. W. G., Steenvoorden, A. C. M.
|
|
<strong>Amino-acid substitutions at codon 13 of the N-ras oncogene in human acute myeloid leukaemia.</strong>
|
|
Nature 315: 726-730, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2989702/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2989702</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2989702" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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|
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[<a href="https://doi.org/10.1038/315726a0" target="_blank">Full Text</a>]
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</li>
|
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<a id="3" class="mim-anchor"></a>
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<a id="Brewin2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brewin, J., Horne, G., Chevassut, T.
|
|
<strong>Genomic landscapes and clonality of de novo AML. (Letter)</strong>
|
|
New Eng. J. Med. 369: 1472-1473, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24106951/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24106951</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24106951" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</li>
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<li>
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<a id="4" class="mim-anchor"></a>
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<a id="{Cancer Genome Atlas Research Network}2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cancer Genome Atlas Research Network.
|
|
<strong>Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia.</strong>
|
|
New Eng. J. Med. 368: 2059-2074, 2013. Note: Erratum: New Eng. J. Med. 369: 98 only, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23634996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23634996</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23634996[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=23634996" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1056/NEJMoa1301689" target="_blank">Full Text</a>]
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</p>
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</div>
|
|
</li>
|
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|
|
<li>
|
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<a id="5" class="mim-anchor"></a>
|
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<a id="Cirstea2010" class="mim-anchor"></a>
|
|
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|
|
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|
|
Cirstea, I. C., Kutsche, K., Dvorsky, R., Gremer, L., Carta, C., Horn, D., Roberts, A. E., Lepri, F., Merbitz-Zahradnik, T., Konig, R., Kratz, C. P., Pantaleoni, F., and 19 others.
|
|
<strong>A restricted spectrum of NRAS mutations cause Noonan syndrome.</strong>
|
|
Nature. Genet. 42: 27-29, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19966803/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19966803</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19966803[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=19966803" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1038/ng.497" target="_blank">Full Text</a>]
|
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|
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</p>
|
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</div>
|
|
</li>
|
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<li>
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<a id="6" class="mim-anchor"></a>
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<a id="Davis1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Davis, M., Malcolm, S., Hall, A., Marshall, C. J.
|
|
<strong>Localisation of the human N-ras oncogene to chromosome 1cen-p21 by in situ hybridisation.</strong>
|
|
EMBO J. 2: 2281-2283, 1983.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6667677/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6667677</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6667677" 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/j.1460-2075.1983.tb01735.x" target="_blank">Full Text</a>]
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Davis, M., Malcolm, S., Hall, A.
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<strong>The N-ras oncogene is located on the short arm of chromosome 1. (Abstract)</strong>
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Cytogenet. Cell Genet. 37: 448-449, 1984.
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<a id="8" class="mim-anchor"></a>
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<a id="De Filippi2009" class="mim-anchor"></a>
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De Filippi, P., Zecca, M., Lisini, D., Rosti, V., Cagioni, C., Carlo-Stella, C., Radi, O., Veggiotti, P., Mastronuzzi, A., Acquaviva, A., D'Ambrosio, A., Locatelli, F., Danesino, C.
|
|
<strong>Germ-line mutation of the NRAS gene may be responsible for the development of juvenile myelomonocytic leukaemia.</strong>
|
|
Brit. J. Haemat. 147: 706-709, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19775298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19775298</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19775298" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1365-2141.2009.07894.x" target="_blank">Full Text</a>]
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<a id="9" class="mim-anchor"></a>
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<a id="de Martinville1984" class="mim-anchor"></a>
|
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|
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de Martinville, B., Cunningham, J. M., Murray, M. J., Francke, U.
|
|
<strong>The N-ras oncogene assigned to chromosome 1 (p31-cen) by somatic cell hybrid analysis. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 37: 531 only, 1984.
|
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|
|
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</p>
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Deka, R., Majumder, P. P., Warren, A. C., Surti, U., Hoffner, L., Hauselman, E., Antonarakis, S. E., Ferrell, R. E., Chakravarti, A.
|
|
<strong>Gene-centromere mapping using ovarian teratomas: results from chromosomes 1p, 13q and 21q. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 45 (suppl.): A137 only, 1989.
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Dessars, B., De Raeve, L. E., Morandini, R., Lefort, A., El Housni, H., Ghanem, G. E., Van den Eynde, B. J., Ma, W., Roseeuw, D., Vassart, G., Libert, F., Heimann, P.
|
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<strong>Genotypic and gene expression studies in congenital melanocytic nevi: insight into initial steps of melanotumorigenesis.</strong>
|
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J. Invest. Derm. 129: 139-147, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18633438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18633438</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18633438" 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/jid.2008.203" target="_blank">Full Text</a>]
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Dracopoli, N. C., Meisler, M. H.
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<strong>Mapping the human amylase gene cluster on the proximal short arm of chromosome 1 using a highly informative (CA)n repeat.</strong>
|
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Genomics 7: 97-102, 1990.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1692298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1692298</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1692298" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/0888-7543(90)90523-w" target="_blank">Full Text</a>]
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|
|
Ekvall, S., Wilbe, M., Dahlgren, J., Legius, E., van Haeringen, A., Westphal, O., Anneren, G., Bondeson, M.-L.
|
|
<strong>Mutation in NRAS in familial Noonan syndrome: case report and review of the literature.</strong>
|
|
BMC Med. Genet. 16: 95, 2015. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26467218/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26467218</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26467218" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1186/s12881-015-0239-1" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Hafner2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hafner, C., Toll, A., Gantner, S., Mauerer, A., Lurkin, I., Acquadro, F., Fernandez-Casado, A., Zwarthoff, E. C., Dietmaier, W., Baselga, E., Parera, E., Vicente, A., Casanova, A., Cigudosa, J., Mentzel, T., Pujol, R. M., Landthaler, M., Real, F. X.
|
|
<strong>Keratinocytic epidermal nevi are associated with mosaic RAS mutations.</strong>
|
|
J. Med. Genet. 49: 249-253, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22499344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22499344</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22499344" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmedgenet-2011-100637" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Haigis2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Haigis, K. M., Kendall, K. R., Wang, Y., Cheung, A., Haigis, M. C., Glickman, J. N., Niwa-Kawakita, M., Sweet-Cordero, A., Sebolt-Leopold, J., Shannon, K. M., Settleman, J., Giovannini, M., Jacks, T.
|
|
<strong>Differential effects of oncogenic K-Ras and N-Ras on proliferation, differentiation and tumor progression in the colon.</strong>
|
|
Nature Genet. 40: 600-608, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18372904/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18372904</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18372904[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=18372904" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng.115" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Hall1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hall, A., Brown, R.
|
|
<strong>Human N-ras: cDNA cloning and gene structure.</strong>
|
|
Nucleic Acids Res. 13: 5255-5268, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2991860/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2991860</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2991860" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/nar/13.14.5255" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Hall1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hall, A., Marshall, C. J., Spurr, N. K., Weiss, R. A.
|
|
<strong>Identification of transforming gene in two human sarcoma cell lines as a new member of the ras gene family located on chromosome 1.</strong>
|
|
Nature 303: 396-400, 1983.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6304521/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6304521</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6304521" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/303396a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Johnson2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Johnson, S. M., Grosshans, H., Shingara, J., Byrom, M., Jarvis, R., Cheng, A., Labourier, E., Reinert, K. L., Brown, D., Slack, F. J.
|
|
<strong>RAS is regulated by the let-7 microRNA family.</strong>
|
|
Cell 120: 635-647, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15766527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15766527</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15766527" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.cell.2005.01.014" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Kinsler2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kinsler, V. A., Thomas, A. C., Ishida, M., Bulstrode, N. W., Loughlin, S., Hing, S., Chalker, J., McKenzie, K., Abu-Amero, S., Slater, O., Chanudet, E., Palmer, R., Morrogh, D., Stanier, P., Healy, E., Sebire, N. J., Moore, G. E.
|
|
<strong>Multiple congenital melanocytic nevi and neurocutaneous melanosis are caused by postzygotic mutations in codon 61 of NRAS.</strong>
|
|
J. Invest. Derm. 133: 2229-2236, 2013. Note: Erratum: J. Invest. Derm. 136: 2326 only, 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23392294/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23392294</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23392294" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/jid.2013.70" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Li2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Li, Q., Bohin, N., Wen, T., Ng, V., Magee, J., Chen, S.-C., Shannon, K., Morrison, S. J.
|
|
<strong>Oncogenic Nras has bimodal effects on stem cells that sustainably increase competitiveness.</strong>
|
|
Nature 504: 143-147, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24284627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24284627</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24284627[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=24284627" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature12830" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Lim2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lim, Y. H., Ovejero, D., Sugarman, J. S., DeKlotz, C. M. C., Maruri, A., Eichenfield, L. F., Kelley, P. K., Juppner, H., Gottschalk, M., Tifft, C. J., Gafni, R. I., Boyce, A. M., and 12 others.
|
|
<strong>Multilineage somatic activating mutations in HRAS and NRAS cause mosaic cutaneous and skeletal lesions, elevated FGF23 and hypophosphatemia.</strong>
|
|
Hum. Molec. Genet. 23: 397-407, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24006476/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24006476</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24006476[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=24006476" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddt429" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Lin2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lin, D. T. S., Conibear, E.
|
|
<strong>ABHD17 proteins are novel protein depalmitoylases that regulate N-Ras palmitate turnover and subcellular localization.</strong>
|
|
eLife 4: e11306, 2015. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26701913/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26701913</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26701913" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.7554/eLife.11306" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Lubbert1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lubbert, M., Mirro, J., Jr., Miller, C. W., Kahan, J., Isaac, G., Kitchingman, G., Mertelsmann, R., Herrmann, F., McCormick, F., Koeffler, H. P.
|
|
<strong>N-ras gene point mutations in childhood acute lymphocytic leukemia correlate with a poor prognosis.</strong>
|
|
Blood 75: 1163-1169, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2407301/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2407301</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2407301" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Marshall1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Marshall, C. J., Hall, A., Weiss, R. A.
|
|
<strong>A transforming gene present in human sarcoma cell lines.</strong>
|
|
Nature 299: 171-173, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6287287/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6287287</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6287287" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/299171a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Matallanas2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Matallanas, D., Arozarena, I., Berciano, M. T., Aaronson, D. S., Pellicer, A., Lafarga, M., Crespo, P.
|
|
<strong>Differences on the inhibitory specificities of H-Ras, K-Ras, and N-Ras (N17) dominant negative mutants are related to their membrane microlocalization.</strong>
|
|
J. Biol. Chem. 278: 4572-4581, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12458225/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12458225</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12458225" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M209807200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Matsuda2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Matsuda, K., Shimada, A., Yoshida, N., Ogawa, A., Watanabe, A., Yajima, S., Iizuka, S., Koike, K., Yanai, F., Kawasaki, K., Yanagimachi, M., Kikuchi, A., and 10 others.
|
|
<strong>Spontaneous improvement of hematologic abnormalities in patients having juvenile myelomonocytic leukemia with specific RAS mutations.</strong>
|
|
Blood 109: 5477-5480, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17332249/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17332249</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17332249" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood-2006-09-046649" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Miller2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Miller, C. A., Wilson, R. K., Ley, T. J.
|
|
<strong>Reply to Brewin et al. (Letter)</strong>
|
|
New Eng. J. Med. 369: 1473 only, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24106950/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24106950</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24106950" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJMc1308782" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Mitchell1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mitchell, E. L. D., Jones, D., White, G. R. M., Varley, J. M., Santibanez Koref, M. F.
|
|
<strong>Determination of the gene order of the three loci CD2, NGFB, and NRAS at human chromosome band 1p13 and refinement of their localisation at the subband level by fluorescence in situ hybridization.</strong>
|
|
Cytogenet. Cell Genet. 70: 183-185, 1995. Note: Erratum: Cytogenet Cell Genet. 71: 306 only, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7789166/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7789166</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7789166" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000134028" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Munke1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Munke, M., Lindgren, V., de Martinville, B., Francke, U.
|
|
<strong>Comparative analysis of mouse-human hybrids with rearranged chromosomes 1 by in situ hybridization and Southern blotting: high-resolution mapping of NRAS, NGFB, and AMY on human chromosome 1.</strong>
|
|
Somat. Cell Molec. Genet. 10: 589-599, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6209808/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6209808</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6209808" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF01535224" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
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|
|
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|
|
|
|
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|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Nazarian2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
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|
|
Nazarian, R., Shi, H., Wang, Q., Kong, X., Koya, R. C., Lee, H., Chen, Z., Lee, M.-K., Attar, N., Sazegar, H., Chodon, T., Nelson, S. F., McArthur, G., Sosman, J. A., Ribas, A., Lo, R. S.
|
|
<strong>Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation.</strong>
|
|
Nature 468: 973-977, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21107323/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21107323</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21107323[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=21107323" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature09626" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Niemela2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Niemela, J. E., Lu, L., Fleisher, T. A., Davis, J., Caminha, I., Natter, M., Beer, L. A., Dowdell, K. C., Pittaluga, S., Raffeld, M., Rao, V. K., Oliveira, J. B.
|
|
<strong>Somatic KRAS mutations associated with a human nonmalignant syndrome of autoimmunity and abnormal leukocyte homeostasis.</strong>
|
|
Blood 117: 2883-2886, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21079152/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21079152</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21079152[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=21079152" 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/10.1182/blood-2010-07-295501" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
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|
|
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|
|
|
|
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|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Nikiforova2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
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|
|
Nikiforova, M. N., Lynch, R. A., Biddinger, P. W., Alexander, E. K., Dorn, G. W., II, Tallini, G., Kroll, T. G., Nikiforov, Y. E.
|
|
<strong>RAS point mutations and PAX8-PPAR-gamma rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma.</strong>
|
|
J. Clin. Endocr. Metab. 88: 2318-2326, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12727991/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12727991</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12727991" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2002-021907" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Nitta1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nitta, N., Ochiai, M., Nagao, M., Sugimura, T.
|
|
<strong>Amino-acid substitution at codon 13 of the N-ras oncogene in rectal cancer in a Japanese patient.</strong>
|
|
Jpn. J. Cancer Res. 78: 21-26, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3102434/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3102434</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3102434" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Oliveira2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
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|
|
Oliveira, J. B., Bidere, N., Niemela, J. E., Zheng, L., Sakai, K., Nix, C. P., Danner, R. L., Barb, J., Munson, P. J., Puck, J. M., Dale, J., Straus, S. E., Fleisher, T. A., Lenardo, M. J.
|
|
<strong>NRAS mutation causes a human autoimmune lymphoproliferative syndrome.</strong>
|
|
Proc. Nat. Acad. Sci. 104: 8953-8958, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17517660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17517660</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17517660[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=17517660" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.0702975104" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
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|
|
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|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Popescu1985" class="mim-anchor"></a>
|
|
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|
|
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|
|
Popescu, N. C., Amsbaugh, S. C., DiPaolo, J. A., Tronick, S. R., Aaronson, S. A., Swan, D. C.
|
|
<strong>Chromosomal localization of three human ras genes by in situ molecular hybridization.</strong>
|
|
Somat. Cell Molec. Genet. 11: 149-155, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3856955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3856955</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3856955" 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/10.1007/BF01534703" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
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|
|
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|
|
|
|
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|
|
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|
|
<a id="Povey1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Povey, S., Morton, N. E., Sherman, S. L.
|
|
<strong>Report of the committee on the genetic constitution of chromosomes 1 and 2 (HGM8).</strong>
|
|
Cytogenet. Cell Genet. 40: 67-106, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3864603/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3864603</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3864603" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000132170" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
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|
|
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|
|
|
|
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|
|
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|
|
<a id="Rabin1984" class="mim-anchor"></a>
|
|
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|
|
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|
|
Rabin, M., Watson, M., Barker, P. E., Ryan, J., Breg, W. R., Ruddle, F. H.
|
|
<strong>NRAS transforming gene maps to region p11-p13 on chromosome 1 by in situ hybridization.</strong>
|
|
Cytogenet. Cell Genet. 38: 70-72, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6705568/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6705568</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6705568" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000132032" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
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|
|
</li>
|
|
|
|
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|
|
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|
|
<a id="Rabin1983" class="mim-anchor"></a>
|
|
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|
|
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|
|
Rabin, M., Watson, M., Barker, P., Ryan, J., Breg, W. R., Ruddle, F. H.
|
|
<strong>Chromosomal assignment of human c-fos and N-ras oncogenes. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 35: 148A only, 1983.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
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|
|
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|
|
<a id="Rocks2005" class="mim-anchor"></a>
|
|
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|
|
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|
|
Rocks, O., Peyker, A., Kahms, M., Verveer, P. J., Koerner, C., Lumbierres, M., Kuhlmann, J., Waldmann, H., Wittinghofer, A., Bastiaens, P. I. H.
|
|
<strong>An acylation cycle regulates localization and activity of palmitoylated Ras isoforms.</strong>
|
|
Science 307: 1746-1752, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15705808/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15705808</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15705808" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1105654" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
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|
|
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|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Ryan1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ryan, J., Barker, P. E., Shimizu, K., Wigler, M., Ruddle, F. H.
|
|
<strong>Chromosomal assignment of a family of human oncogenes.</strong>
|
|
Proc. Nat. Acad. Sci. 80: 4460-4463, 1983.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6576347/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6576347</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6576347" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.80.14.4460" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
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|
|
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|
|
|
|
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|
|
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|
|
<a id="Takahashi2006" class="mim-anchor"></a>
|
|
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|
|
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|
|
Takahashi, C., Contreras, B., Iwanaga, T., Takegami, Y., Bakker, A., Bronson, R. T., Noda, M., Loda, M., Hunt, J. L., Ewen, M. E.
|
|
<strong>Nras loss induces metastatic conversion of Rb1-deficient neuroendocrine thyroid tumor.</strong>
|
|
Nature Genet. 38: 118-123, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16369533/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16369533</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16369533" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng1703" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
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|
|
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|
|
|
|
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|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Taparowsky1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
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|
|
Taparowsky, E., Shimizu, K., Goldfarb, M., Wigler, M.
|
|
<strong>Structure and activation of the human N-ras gene.</strong>
|
|
Cell 34: 581-586, 1983.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6616621/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6616621</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6616621" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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|
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[<a href="https://doi.org/10.1016/0092-8674(83)90390-2" target="_blank">Full Text</a>]
|
|
|
|
|
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|
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|
|
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|
|
|
|
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|
|
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|
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|
|
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|
|
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|
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Vasko, V., Ferrand, M., Di Cristofaro, J., Carayon, P., Henry, J. F., De Micco, C.
|
|
<strong>Specific pattern of RAS oncogene mutations in follicular thyroid tumors.</strong>
|
|
J. Clin. Endocr. Metab. 88: 2745-2752, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12788883/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12788883</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12788883" 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/10.1210/jc.2002-021186" target="_blank">Full Text</a>]
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|
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|
|
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|
|
|
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|
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|
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<a id="Yuasa1984" class="mim-anchor"></a>
|
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|
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|
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Yuasa, Y., Gol, R. A., Chang, A., Chiu, I.-M., Reddy, E. P., Tronick, S. R., Aaronson, S. A.
|
|
<strong>Mechanism of activation of an N-ras oncogene of SW-1271 human lung carcinoma cells.</strong>
|
|
Proc. Nat. Acad. Sci. 81: 3670-3674, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6587382/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6587382</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6587382" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.81.12.3670" target="_blank">Full Text</a>]
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Bao Lige - updated : 04/19/2018
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Joanna S. Amberger - updated : 09/25/2017<br>Ada Hamosh - updated : 11/24/2014<br>Cassandra L. Kniffin - updated : 11/12/2014<br>Cassandra L. Kniffin - updated : 4/16/2014<br>Ada Hamosh - updated : 2/5/2014<br>Ada Hamosh - updated : 11/25/2013<br>Ada Hamosh - updated : 7/9/2013<br>Cassandra L. Kniffin - updated : 1/30/2013<br>Cassandra L. Kniffin - updated : 8/1/2011<br>Ada Hamosh - updated : 1/21/2011<br>Cassandra L. Kniffin - updated : 1/19/2010<br>Ada Hamosh - updated : 7/29/2008<br>Carol A. Bocchini - updated : 7/25/2008<br>Cassandra L. Kniffin - updated : 12/20/2007<br>Ada Hamosh - updated : 6/29/2007<br>Patricia A. Hartz - updated : 4/10/2006<br>Victor A. McKusick - updated : 12/27/2005<br>Stylianos E. Antonarakis - updated : 3/28/2005<br>John A. Phillips, III - updated : 9/2/2003<br>John A. Phillips, III - updated : 8/28/2003<br>Victor A. McKusick - updated : 9/26/2001
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<a id="creationDate" class="mim-anchor"></a>
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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Creation Date:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 6/2/1986
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 08/23/2019
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<div class="row collapse" id="mimCollapseEditHistory">
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<span class="mim-text-font">
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carol : 09/19/2018<br>carol : 04/27/2018<br>mgross : 04/19/2018<br>carol : 09/26/2017<br>carol : 09/26/2017<br>carol : 09/25/2017<br>alopez : 09/01/2015<br>alopez : 5/21/2015<br>alopez : 11/24/2014<br>alopez : 11/24/2014<br>carol : 11/18/2014<br>mcolton : 11/13/2014<br>ckniffin : 11/12/2014<br>carol : 4/18/2014<br>carol : 4/17/2014<br>ckniffin : 4/16/2014<br>alopez : 2/5/2014<br>alopez : 11/25/2013<br>alopez : 7/9/2013<br>alopez : 7/9/2013<br>alopez : 2/6/2013<br>ckniffin : 1/30/2013<br>terry : 11/29/2012<br>carol : 2/6/2012<br>wwang : 8/9/2011<br>ckniffin : 8/1/2011<br>carol : 6/17/2011<br>alopez : 1/24/2011<br>terry : 1/21/2011<br>alopez : 1/28/2010<br>ckniffin : 1/19/2010<br>ckniffin : 1/19/2010<br>carol : 8/15/2008<br>alopez : 7/31/2008<br>terry : 7/29/2008<br>carol : 7/28/2008<br>carol : 7/25/2008<br>wwang : 6/5/2008<br>carol : 5/14/2008<br>wwang : 1/30/2008<br>ckniffin : 12/20/2007<br>alopez : 7/2/2007<br>terry : 6/29/2007<br>mgross : 4/14/2006<br>terry : 4/10/2006<br>alopez : 1/9/2006<br>alopez : 12/28/2005<br>terry : 12/27/2005<br>mgross : 3/28/2005<br>alopez : 9/11/2003<br>alopez : 9/10/2003<br>alopez : 9/2/2003<br>alopez : 8/28/2003<br>carol : 10/4/2001<br>mcapotos : 10/3/2001<br>terry : 9/26/2001<br>carol : 7/30/1998<br>mark : 10/20/1995<br>warfield : 4/12/1994<br>supermim : 3/16/1992<br>carol : 3/8/1992<br>carol : 2/1/1992<br>carol : 1/31/1992
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<h3>
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<span class="mim-font">
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<strong>*</strong> 164790
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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NRAS PROTOONCOGENE, GTPase; NRAS
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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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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</p>
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<div>
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<h4>
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<span class="mim-font">
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NEUROBLASTOMA RAS VIRAL ONCOGENE HOMOLOG<br />
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ONCOGENE NRAS; NRAS1
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</h4>
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</div>
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<br />
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: NRAS</em></strong>
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</span>
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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: 1p13.2
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Genomic coordinates <span class="small">(GRCh38)</span> : 1:114,704,469-114,716,771 </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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<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="8">
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<span class="mim-font">
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1p13.2
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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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?RAS-associated autoimmune lymphoproliferative syndrome type IV, somatic
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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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614470
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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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</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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<tr>
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<td>
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<span class="mim-font">
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Colorectal cancer, somatic
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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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114500
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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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</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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<tr>
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<td>
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<span class="mim-font">
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Epidermal nevus, somatic
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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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162900
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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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</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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<tr>
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<td>
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<span class="mim-font">
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Melanocytic nevus syndrome, congenital, somatic
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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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137550
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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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</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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<tr>
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<td>
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<span class="mim-font">
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Neurocutaneous melanosis, somatic
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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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249400
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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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</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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<tr>
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<td>
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<span class="mim-font">
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Noonan syndrome 6
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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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613224
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</span>
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</td>
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<td>
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<span class="mim-font">
|
|
Autosomal dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
|
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<td>
|
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<span class="mim-font">
|
|
Schimmelpenning-Feuerstein-Mims syndrome, somatic mosaic
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
163200
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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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</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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<tr>
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<td>
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<span class="mim-font">
|
|
Thyroid carcinoma, follicular, somatic
|
|
</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
188470
|
|
</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
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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>
|
|
</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>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>Marshall et al. (1982) identified a gene with transforming activity in 2 different human sarcoma cell lines, a fibrosarcoma (HT1080) and an embryonal rhabdomyosarcoma (RD). Hall et al. (1983) identified this gene as a member of the RAS gene family and designated it N-RAS 'after consultation with Wigler and with Weinberg.' They found that NRAS was also activated in a promyelocytic leukemia cell line (HL60) and a neuroblastoma cell line (SK-H-SH). NRAS was present at the same levels in normal fibroblasts and tumor cells. Hall and Brown (1985) identified 2 main NRAS transcripts of 4.3 kb and 2 kb. </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>Gene Structure</strong>
|
|
</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>Hall and Brown (1985) determined that the NRAS gene contains 7 exons. </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>Mapping</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>By restriction mapping and Southern blot analysis, Hall et al. (1983) mapped the NRAS gene to chromosome 1. By in situ hybridization, Davis et al. (1983) assigned the NRAS gene to the short arm of chromosome 1. A concentration of grains was observed just above the centromere in band 1p13. They commented on the wide dispersion of the oncogenes in the RAS family; each of the 5 mapped to date was on a separate chromosome. Ryan et al. (1983) confirmed assignment of HRAS (190020) to chromosome 11, KRAS2 (190070) to chromosome 12, and NRAS to chromosome 1. Addendum in proof indicated that the same laboratory had assigned NRAS1 to 1p21-cen. De Martinville et al. (1984) assigned NRAS to 1p31-cen. By somatic cell hybrid studies and by in situ hybridization, Rabin et al. (1984) assigned the NRAS gene to 1p13-p11. By in situ hybridization, Popescu et al. (1985) also assigned the NRAS locus to 1p13-p11. Povey et al. (1985) reviewed the conflicting evidence on the site of NRAS on 1p. They found evidence favoring both 1p22 and 1p12-p11. Dracopoli and Meisler (1990) concluded from linkage analysis and pulsed field gel electrophoresis that TSHB (188540), NGFB (162030), and NRAS form a tightly linked gene cluster located in the same chromosomal band. Their location proximal to the AMY2B gene in 1p21 and close linkage to the alpha-satellite centromeric repeat D1Z5 provided strong evidence that the correct assignment for these 3 loci is 1p13 and not 1p22. Mitchell et al. (1995) localized NRAS to 1p13.2 and CD2 (186990) and NGFB to 1p13.1. They concluded that the order is as follows: cen--CD2--NGFB--NRAS--tel. </p><p>Using teratomas (see 166950) as a means of 'centromere mapping,' Deka et al. (1989) estimated the NRAS-centromere distance (y) to be 0.30.</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>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>Substitution of ser17 with asn (S17N) in any of the RAS proteins produces dominant-inhibitory proteins with higher affinities for exchange factors than normal RAS. These mutants cannot interact with downstream effectors and therefore form unproductive complexes, preventing activation of endogenous RAS. Using experiments in COS-7 cells, mouse fibroblasts, and canine kidney cells, Matallanas et al. (2003) found that the Hras, Kras, and Nras S17N mutants exhibited distinct inhibitory effects that appeared to be due largely to their specific membrane localizations. The authors demonstrated that Hras is present in caveolae, lipid rafts, and bulk disordered membranes, whereas Kras and Nras are present primarily in disordered membranes and lipid rafts, respectively. Thus, the Hras S17N mutant inhibited activation of all 3 wildtype RAS isoforms, the Kras S17N mutant inhibited wildtype Kras and the portion of Hras in disordered membranes, and the Nras S17N mutant inhibited wildtype Nras and the portion of Hras in lipid rafts. </p><p>Rocks et al. (2005) showed that the specific subcellular distribution of HRAS and NRAS guanosine triphosphate-binding proteins is generated by a constitutive de/reacylation cycle that operates on palmitoylated proteins, driving their rapid exchange between the plasma membrane and the Golgi apparatus. Depalmitoylation redistributes farnesylated Ras in all membranes, followed by repalmitoylation and trapping of Ras at the Golgi, from where it is redirected to the plasma membrane via the secretory pathway. This continuous cycle prevents Ras from nonspecific residence on endomembranes, thereby maintaining the specific intracellular compartmentalization. Rocks et al. (2005) found that the de/reacylation cycle also initiates Ras activation at the Golgi by transport of plasma membrane-localized Ras guanosine triphosphate. Different de/repalmitoylation kinetics account for isoform-specific activation responses to growth factors. </p><p>Haigis et al. (2008) used genetically engineered mice to determine whether and how the related oncogenes Kras (190070) and Nras regulate homeostasis and tumorigenesis in the colon. Expression of Kras(G12D) in the colonic epithelium stimulated hyperproliferation in a Mek (see 176872)-dependent manner. Nras(G12D) did not alter the growth properties of the epithelium, but was able to confer resistance to apoptosis. In the context of an Apc (611731)-mutant colonic tumor, activation of Kras led to defects in terminal differentiation and expansion of putative stem cells within the tumor epithelium. This Kras tumor phenotype was associated with attenuated signaling through the MAPK pathway (see 176872), and human colon cancer cells expressing mutant Kras were hypersensitive to inhibition of Raf (see 164760) but not Mek. Haigis et al. (2008) concluded that their studies demonstrated clear phenotypic differences between mutant Kras and Nras, and suggested that the oncogenic phenotype of mutant Kras might be mediated by noncanonical signaling through Ras effector pathways. </p><p>Nazarian et al. (2010) showed that acquired resistance of BRAF(V600E) (164757.0001)-positive melanomas to PLX4032, a novel class I RAF-selective inhibitor, develops by mutually exclusive PDGFRB (173410) upregulation or NRAS mutations but not through secondary mutations in BRAF(V600E). Nazarian et al. (2010) used PLX4032-resistant sublines artificially derived from BRAF(V600E)-positive melanoma cell lines and validated key findings in PLX4032-resistant tumors and tumor-matched, short-term cultures from clinical trial patients. Induction of PDGFRB RNA, protein, and tyrosine phosphorylation emerged as a dominant feature of acquired PLX4032 resistance in a subset of melanoma sublines, patient-derived biopsies, and short-term cultures. PDGFRB-upregulated tumor cells had low activated RAS levels and, when treated with PLX4032, did not reactivate the MAPK (see 176872) pathway significantly. In another subset, high levels of activated NRAS resulting from mutations led to significant MAPK pathway reactivation upon PLX4032 treatment. Knockdown of PDGFRB or NRAS reduced growth of the respective PLX4032-resistant subsets. Overexpression of PDGFRB or mutated NRAS conferred PLX4032 resistance to PLX4032-sensitive parental cell lines. Importantly, Nazarian et al. (2010) showed that MAPK reactivation predicts MEK inhibitor sensitivity. Thus, Nazarian et al. (2010) concluded that melanomas escape BRAF(V600E) targeting not through secondary BRAF(V600E) mutations but via receptor tyrosine kinase (RTK)-mediated activation of alternative survival pathway(s) or activated RAS-mediated reactivation of the MAPK pathway, suggesting additional therapeutic strategies. </p><p>Using a dual pulse-chase strategy comparing palmitate and protein half-lives in transfected COS-7 cells, followed by inhibitor studies, Lin and Conibear (2015) showed that members of the ABHD17 family (see ABHD17A, 617942) were common targets of depalmitoylation inhibitors and could accelerate palmitate turnover on PSD95 (DLG4; 602887) and NRAS in COS-7 cells. ABHD17A relocalized depalmitoylated NRAS from plasma membrane to internal cellular membranes in COS-7 cells. Knockdown studies showed that the endogenous ABHD17 proteins redundantly depalmitoylated NRAS in HEK293T cells. Lin and Conibear (2015) concluded that ABHD17 proteins regulate NRAS palmitate turnover and subcellular localization. </p>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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<span class="mim-text-font">
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<p><strong><em>Role in Carcinoma</em></strong></p><p>
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Vasko et al. (2003) performed a pooled analysis of 269 mutations in HRAS, KRAS, and NRAS found in follicular thyroid tumors (FTC; see 188550) garnered from 39 previous studies. Mutations proved significantly less frequent when detected with than without direct sequencing (12.3% vs 17%). The rates of mutation involving NRAS exon 1 and KRAS exon 2 was less than 1%. Mutations of codon 61 of NRAS were significantly more frequent in follicular tumors (19%) than in papillary cancers (5%) and significantly more frequent in malignant (25%) than in benign (14%) tumors. HRAS mutations in codons 12/13 were found in 2 to 3% of all types of tumors, but HRAS mutations in codon 61 were observed in only 1.4% of tumors, and almost all of them were malignant. KRAS mutations in exon 1 were found more often in papillary than follicular cancers (2.7% vs 1.6%) and were sometimes correlated with special epidemiologic circumstances. The second part of this study involved analysis of 80 follicular tumors from patients living in Marseille (France) and Kiev (Ukraine). HRAS mutations in codons 12/13 were found in 12.5% of common adenomas and 1 follicular carcinoma (2.9%). Mutations of codon 61 of NRAS occurred in 23.3% and 17.6% of atypical adenomas and follicular carcinomas, respectively. The authors concluded that their results confirmed the predominance of mutations of codon 61 of NRAS in thyroid follicular tumors and their correlation with malignancy. </p><p>Nikiforova et al. (2003) analyzed a series of 88 conventional follicular and Hurthle cell thyroid tumors for RAS (HRAS, NRAS, or KRAS) mutations and PAX8 (167415)-PPARG (601487) rearrangements using molecular methods and for galectin-3 (153619) and mesothelioma antibody HBME-1 expression by immunohistochemistry. Forty-nine percent of conventional follicular carcinomas had RAS mutations, 36% had PAX8-PPARG rearrangement, and only 1 (3%) had both. Of follicular adenomas, 48% had RAS mutations, 4% had PAX8-PPARG rearrangement, and 48% had neither. Follicular carcinomas with RAS mutations most often displayed an HBME-1-positive/galectin-3-negative immunophenotype and were either minimally or overtly invasive. Hurthle cell tumors infrequently had PAX8-PPARG rearrangement or RAS mutations. </p><p>Johnson et al. (2005) found that the 3 human RAS genes, HRAS KRAS, and NRAS, contain multiple let-7 (see 605386) miRNA complementary sites in their 3-prime UTRs that allow let-7 miRNA to regulate their expression. Let-7 expression was lower in lung tumors than in normal lung tissue, whereas expression of the RAS proteins was significantly higher in lung tumors, suggesting a possible mechanism for let-7 in cancer. </p><p><strong><em>Role In Hematologic Malignancies</em></strong></p><p>
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Using the allele-specific amplification method (ARMS), a highly sensitive 1-stage allele-specific PCR, Bezieau et al. (2001) evaluated the incidence of NRAS- and KRAS2-activating mutations (in codons 12, 13, and 61) in 62 patients with monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM), or primary plasma cell leukemia (PPCL), and in human myeloma cell lines (HMCL). Mutations in one or the other gene, or in both, were found in 54.5% of MM patients at diagnosis (but in 81% at the time of relapse), 50% of PPCL patients, and 50% of 16 HMCL patients. In contrast, the occurrence of such mutations was very low in MGUS and indolent MM (12.5%). KRAS2 mutations were always more frequent than NRAS mutations. Bezieau et al. (2001) concluded that these early mutations may play a major role in the oncogenesis of multiple myeloid myeloma and primary plasma cell leukemia. </p><p>In white blood cells derived from 8 patients with juvenile myelomonocytic leukemia (JMML; 607785), Matsuda et al. (2007) identified 5 different somatic mutations in the NRAS gene (see, e.g., G12D, 164790.0007 and G13D, 164790.0003). Each patient carried a single somatic mutation. The patients were ascertained from a cohort of 80 children with JMML. </p><p>The Cancer Genome Atlas Research Network (2013) analyzed the genomes of 200 clinically annotated adult cases of de novo acute myeloid leukemia (AML; 601626), using either whole-genome sequencing (50 cases) or whole-exome sequencing (150 cases), along with RNA and microRNA sequencing and DNA methylation analysis. The Cancer Genome Atlas Research Network (2013) identified recurrent mutations in the NRAS or KRAS genes in 23 (12%) of 200 samples. </p><p>Brewin et al. (2013) noted that the study of the Cancer Genome Atlas Research Network (2013) did not reveal which mutations occurred in the founding clone, as would be expected for an initiator of disease, and which occurred in minor clones, which subsequently drive disease. Miller et al. (2013) responded that NRAS was among several genes in their study whose mutations were often found in subclones, suggesting that they are often cooperating mutations. The authors also identified other genes that contained mutations they considered probable initiators. </p><p><strong><em>RAS-Associated Autoimmune Leukoproliferative Disorder</em></strong></p><p>
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Oliveira et al. (2007) identified a heterozygous mutation in the NRAS gene (G13D; 164790.0003) in a 49-year-old patient with RAS-associated autoimmune leukoproliferative disorder (RALD; 614470). The patient had a lifelong overexpansion of lymphocytes, childhood leukemia, and early adulthood lymphoma, both successfully treated. He had increased serum CD4-/CD8- alpha/beta T cells and follicular hyperplasia of the lymph nodes. Niemela et al. (2010) stated that the NRAS mutation found by Oliveira et al. (2007) was a somatic mutation. </p><p><strong><em>Noonan Syndrome 6</em></strong></p><p>
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Cirstea et al. (2010) identified 1 of 2 different heterozygous mutations in the NRAS gene (T50I; 164790.0004 and G60E; 164790.0005) in 5 patients, including a mother and son, with Noonan syndrome-6 (NS6; 613224). The mutations were de novo in 3 patients. In vitro functional expression studies showed that the mutations resulted in enhanced stimulus-dependent MAPK activation. The patients were part of a larger study of 917 affected individuals who were negative for previously known Noonan-associated gene mutations, suggesting that NRAS mutations are a rare cause of Noonan syndrome. </p><p><strong><em>Congenital Melanocytic Nevus Syndrome</em></strong></p><p>
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Dessars et al. (2009) identified a somatic NRAS mutation in samples from 19 (70%) of 27 patients with congenital melanocytic nevi (CMNS; 137550): 14 nevi carried a Q61K mutation (164790.0008), 4 carried a Q61R mutation (164790.0002), and 1 carried a G13R mutation (164790.0001). </p><p>Kinsler et al. (2013) identified somatic oncogenic missense mutations affecting codon 61 of the NRAS gene in affected cutaneous and neurologic tissues from 12 of 15 patients with congenital melanocytic nevus syndrome and/or neurocutaneous melanosis (NCMS; 249400). Affected skin samples from 10 of 13 patients carried a somatic heterozygous mutation, including 8 with Q61K and 2 with Q61R. The same codon 61 mutation was found in each of the anatomically separate melanocytic nevi from the same patient. In addition, all 11 neurologic samples from 5 patients from whom neurologic tissue was available were positive for a somatic Q61K mutation; this included both melanocytic and nonmelanocytic tissue, such as a choroid plexus papilloma and meningioma. In patients with both neurologic and skin samples available, the same mutation was present in both affected tissues. None of the patients carried an NRAS mutation in the blood. Pre- and post-malignant skin tissue was available from a patient with malignant melanoma, which showed a progression from heterozygosity to homozygosity for the Q61K mutation with the onset of malignancy. Mutations at codon 61 in the NRAS gene affect the guanosine triphosphate-binding site and result in constitutive activation of NRAS. Kinsler et al. (2013) concluded that multiple congenital melanocytic nevi and neuromelanosis, as well as nonmelanocytic CNS lesions, result from somatic mosaicism, and that the mutation probably occurs in a progenitor cell in the developing neural crest or neuroectoderm. The findings also suggested that these mutations may be lethal in the germline. Three of the original 15 patients with CMNS did not have NRAS mutations. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</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>Mutations in the RB1 gene (614041) predispose humans and mice to tumor development. Takahashi et al. (2006) assessed the effect of Nras loss on tumor development in Rb1 heterozygous mice. Loss of 1 or 2 Nras alleles significantly reduced the severity of pituitary tumors arising in Rb1 +/- animals by enhancing their differentiation. By contrast, C-cell thyroid adenomas occurring in Rb1 +/- mice progressed to metastatic medullary carcinomas after loss of Nras. In Rb1/Nras doubly heterozygous mice, distant medullary thyroid carcinoma metastases were associated with loss of the remaining wildtype Nras allele. Loss of Nras in Rb1-deficient C cells resulted in elevated Ras homolog family A (RhoA) activity, and this was causally linked to the invasiveness and metastatic behavior of these cells. These findings suggested that the loss of the protooncogene Nras in certain cellular contexts can promote malignant tumor progression. </p>
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</span>
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<div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>8 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 RECTAL CANCER, SOMATIC</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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MELANOCYTIC NEVUS SYNDROME, CONGENITAL, SOMATIC, INCLUDED
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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NRAS, GLY13ARG
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<br />
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SNP: rs121434595,
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ClinVar: RCV000014913, RCV000114743, RCV000438070, RCV001781267, RCV004767008
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>Nitta et al. (1987) found a G-to-C point mutation at the first letter of codon 13 in the NRAS gene as the presumed basis for activation of the gene in a case of rectal cancer (see 114500). The point mutation resulted in the substitution of arginine for glycine. </p><p>Dessars et al. (2009) identified a heterozygous somatic G13R mutation in 1 of 27 congenital melanocytic nevi (137550). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 THYROID CARCINOMA, FOLLICULAR, SOMATIC</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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EPIDERMAL NEVUS, SOMATIC, INCLUDED<br />
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MELANOCYTIC NEVUS SYNDROME, CONGENITAL, SOMATIC, INCLUDED<br />
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NEUROCUTANEOUS MELANOSIS, SOMATIC, INCLUDED<br />
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SCHIMMELPENNING-FEUERSTEIN-MIMS SYNDROME, SOMATIC MOSAIC, INCLUDED
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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NRAS, GLN61ARG
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<br />
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SNP: rs11554290,
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ClinVar: RCV000014914, RCV000032847, RCV000037574, RCV000114744, RCV000114745, RCV000148032, RCV000413804, RCV003992155, RCV004668730
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>Nikiforova et al. (2003) found that the CAA-CGA mutation of NRAS codon 61, resulting in a gln-to-arg change (Q61R), was present in 70% (12) of follicular carcinomas (see 188550) and 55% (6) of follicular adenomas studied. </p><p>Hafner et al. (2012) identified a somatic Q61R mutation in 1 of 72 keratinocytic epidermal nevi (162900). </p><p>Dessars et al. (2009) identified a somatic Q61R mutation in 4 of 27 congenital melanocytic nevi (137550). </p><p>In affected skin samples from 2 of 13 patients with congenital melanocytic nevus syndrome (CMNS; 137550), Kinsler et al. (2013) identified a somatic heterozygous c.182C-A transversion in the NRAS gene, resulting in the Q61R mutation. The substitution occurred in the guanosine triphosphate-binding site and was predicted to result in constitutive activation of NRAS. One of the samples from 1 of the patients showed homozygosity for the Q61R mutation: this patient later developed fatal leptomeningeal melanocytic disease (NCMS; 249400) that was indistinguishable from malignant melanoma. </p><p>Lim et al. (2014) identified a Caucasian female who presented at birth with linear epidermal nevi (SFM; 163200) restricted to the left side of her body and distributed from neck to calf. Histopathology showed acanthosis and papillomatosis. A femur radiograph taken when the patient was 7 years of age revealed dysplastic bone with a sclerotic appearance. At a younger age, she had lesions that were more lytic in nature. In a second patient with this mutation who had congenital melanocytic nevus syndrome (137550), Lim et al. (2014) showed that elevated serum FGF23 (605380) originated from dysplastic bone with the Q61R mutation. The mutation was absent from normal bone. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 JUVENILE MYELOMONOCYTIC LEUKEMIA, SOMATIC</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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RAS-ASSOCIATED AUTOIMMUNE LEUKOPROLIFERATIVE DISORDER, SOMATIC (1 patient), INCLUDED<br />
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NOONAN SYNDROME 6, INCLUDED
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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NRAS, GLY13ASP
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<br />
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SNP: rs121434596,
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gnomAD: rs121434596,
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ClinVar: RCV000014915, RCV000022690, RCV000144962, RCV000157672, RCV001293767, RCV005089258
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In white blood cells derived from 2 unrelated children with juvenile myelomonocytic leukemia (JMML; 607785), Matsuda et al. (2007) identified a somatic heterozygous G-to-A transition in the NRAS gene, resulting in a gly13-to-asp (G13D) substitution. </p><p>Oliveira et al. (2007) identified a heterozygous G-to-A transition in the NRAS gene, resulting in a gly13-to-asp (G13D) substitution, in a 49-year-old patient with RAS-associated autoimmune leukoproliferative disorder (RALD; 614470). The patient had a lifelong overexpansion of lymphocytes and a history of childhood leukemia, and early adulthood lymphoma, both successfully treated. There were no developmental defects. Laboratory studies showed increased serum alpha/beta CD4-/CD8- T cells and lymph node follicular hyperplasia. There was no evidence of CD95 (134637)-mediated apoptosis, but the patient's lymphocytes resisted death by IL2 (147680) withdrawal, indicating a specific defect in lymphocyte apoptosis. Further studies of the patient's cells indicated a decrease of the proapoptotic protein BIM (BCL2L11; 603827), which is critical for withdrawal-induced mitochondrial apoptosis. The mutation was found in the patient's lymphoblasts, peripheral blood mononuclear cells, monocytes, EBV-transformed B cells, and buccal epithelial cells. It was not present in the patient's unaffected relatives, suggesting de novo occurrence. The patient had no developmental abnormalities or features of Noonan syndrome. Oliveira et al. (2007) noted that the same mutation had been identified somatically in myeloid and lymphoid malignancies (Bos et al., 1985; Lubbert et al., 1990). Niemela et al. (2010) stated that the NRAS mutation found by Oliveira et al. (2007) was a somatic mutation. </p><p>De Filippi et al. (2009) identified a de novo germline heterozygous G13D substitution in the NRAS gene in a male infant who presented at age 2 months with juvenile myelomonocytic leukemia (JMML; 607785) and was later noted to have dysmorphic features suggestive of, but not diagnostic of, Noonan syndrome (NS6; 613224). Features included short stature, relative macrocephaly, high forehead, epicanthal folds, long eyebrows, low nasal bridge, low-set ears, 2 cafe-au-lait spots, and low scores on performance tasks. Cardiac studies were normal. There were no hematologic abnormalities related to RALD in this patient. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 NOONAN SYNDROME 6</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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NRAS, THR50ILE
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<br />
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SNP: rs267606921,
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ClinVar: RCV000014916, RCV000208537, RCV000211835, RCV000463185
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 unrelated boys with Noonan syndrome-6 (NS6; 613224), Cirstea et al. (2010) identified a de novo heterozygous 149C-T transition in exon 3 of the NRAS gene, resulting in a thr50-to-ile (T50I) substitution in a conserved residue located in the beta-2-beta-3 loop connecting the 2 switch regions. In vitro functional expression studies showed that the mutant protein resulted in enhanced downstream phosphorylation in the presence of serum, but did not substantially affect intrinsic GTPase activity. Molecular modeling indicated that thr50 interacts with the polar heads of membrane phospholipids and is an integral part of a region that controls RAS membrane orientation. Cirstea et al. (2010) hypothesized that the T50I substitution might alter RAS orientation, increase the interaction of GTP-bound RAS with its effectors, and enhance a downstream signal flow consistent with a gain of function. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0005 NOONAN SYNDROME 6</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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NRAS, GLY60GLU
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<br />
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SNP: rs267606920,
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gnomAD: rs267606920,
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ClinVar: RCV000014917, RCV000158982, RCV000208552, RCV001382056, RCV003415702, RCV004984642
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 3 patients from 2 unrelated families with Noonan syndrome-6 (NS6; 613224), Cirstea et al. (2010) identified a heterozygous 179G-A transition in exon 3 of the NRAS gene, resulting in a gly60-to-glu (G60E) substitution in a conserved residue in the switch 2 region. One proband had a de novo mutation, whereas the other inherited it from his affected mother. In vitro functional expression studies showed that the mutant protein resulted in enhanced downstream phosphorylation in the presence of serum, and that the G60E mutant NRAS protein accumulated constitutively in the active GTP-bound form, although it appeared to be resistant to GAP stimulation. </p><p>By targeted next-generation sequencing in a father and daughter with Noonan syndrome, Ekvall et al. (2015) identified heterozygosity for the G60E mutation in the NRAS gene. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0006 EPIDERMAL NEVUS, SOMATIC</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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NRAS, PRO34LEU
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<br />
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SNP: rs397514553,
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ClinVar: RCV000032848, RCV000208568
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>Hafner et al. (2012) identified a somatic pro34-to-leu (P34L) mutation in the NRAS gene in 1 of 72 keratinocytic epidermal nevi (162900). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0007 EPIDERMAL NEVUS, SOMATIC</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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JUVENILE MYELOMONOCYTIC LEUKEMIA, SOMATIC, INCLUDED
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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NRAS, GLY12ASP
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<br />
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SNP: rs121913237,
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gnomAD: rs121913237,
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ClinVar: RCV000032849, RCV000144963, RCV000158980, RCV001781333, RCV001813214, RCV001852659, RCV003221788, RCV003415756, RCV004018703
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>Hafner et al. (2012) identified a somatic gly12-to-asp (G12D) mutation in the NRAS gene in 1 of 72 keratinocytic epidermal nevi (162900). </p><p>In white blood cells derived from 2 unrelated children with juvenile myelomonocytic leukemia (JMML; 607785), Matsuda et al. (2007) identified a somatic heterozygous G-to-A transition in the NRAS gene, resulting in a gly12-to-asp (G12D) substitution. </p><p>Li et al. (2013) showed that a single allele of oncogenic Nras(G12D) increases hematopoietic stem cell (HSC) proliferation and also increases reconstituting and self-renewal potential upon serial transplantation in irradiated mice, all prior to leukemia initiation. Nras(G12D) also confers long-term self-renewal potential to multipotent progenitors. Li et al. (2013) found that Nras(G12D) had a bimodal effect on HSCs, increasing the frequency with which some HSCs divide and reducing the frequency with which others divide. This mirrored bimodal effects on reconstituting potential, as rarely dividing Nras(G12D) HSCs outcompeted wildtype HSCs, whereas frequently dividing Nras(G12D) HSCs did not. Nras(G12D) caused these effects by promoting STAT5 (601511) signaling, inducing different transcriptional responses in different subsets of HSCs. Li et al. (2013) concluded that 1 signal can therefore increase HSC proliferation, competitiveness, and self-renewal through bimodal effects on HSC gene expression, cycling, and reconstituting potential. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0008 MELANOCYTIC NEVUS SYNDROME, CONGENITAL, SOMATIC</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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NEUROCUTANEOUS MELANOSIS, SOMATIC, INCLUDED
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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NRAS, GLN61LYS
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<br />
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SNP: rs121913254,
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gnomAD: rs121913254,
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ClinVar: RCV000114746, RCV000144964, RCV000626456, RCV000662267, RCV000696329, RCV001092890, RCV004668769
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>Dessars et al. (2009) identified a somatic gln61-to-lys (Q61K) mutation in the NRAS gene in 14 of 27 congenital melanocytic nevi (137550). </p><p>In affected skin samples from 8 of 13 patients with congenital melanocytic nevus syndrome (CMNS; 137550), including 4 with neurocutaneous melanosis (NCMS; 249400), Kinsler et al. (2013) identified a somatic heterozygous c.181C-A transversion in the NRAS gene, resulting in a gln61-to-lys (Q61K) substitution in the guanosine triphosphate-binding domain. The mutation was predicted to result in constitutive activation of NRAS. Neurologic samples from 5 patients from whom tissue was available were positive for a somatic Q61K mutation, and the same mutation was present in both neurologic and skin samples when available. Kinsler et al. (2013) concluded that multiple congenital melanocytic nevi and neuromelanosis, as well as associated nonmelanocytic CNS lesions, result from somatic mosaicism, and that the mutation probably occurs in a progenitor cell in the developing neural crest or neuroectoderm. The findings also suggested that the mutation may be lethal in the germline. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>See Also:</strong>
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</span>
|
|
</h4>
|
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<span class="mim-text-font">
|
|
Davis et al. (1984); Munke et al. (1984); Rabin et al. (1983);
|
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Taparowsky et al. (1983); Yuasa et al. (1984)
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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|
<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Bezieau, S., Devilder, M.-C., Avet-Loiseau, H., Mellerin, M.-P., Puthier, D., Pennarun, E., Rapp, M.-J., Harousseau, J.-L., Moisan, J.-P., Bataille, R.
|
|
<strong>High incidence of N and K-Ras activating mutations in multiple myeloma and primary plasma cell leukemia at diagnosis.</strong>
|
|
Hum. Mutat. 18: 212-224, 2001.
|
|
|
|
|
|
[PubMed: 11524732]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.1177]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
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<p class="mim-text-font">
|
|
Bos, J. L., Toksoz, D., Marshall, C. J., Verlaan-de Vries, M., Veeneman, G. H., van der Eb, A. J., van Boom, J. H., Janssen, J. W. G., Steenvoorden, A. C. M.
|
|
<strong>Amino-acid substitutions at codon 13 of the N-ras oncogene in human acute myeloid leukaemia.</strong>
|
|
Nature 315: 726-730, 1985.
|
|
|
|
|
|
[PubMed: 2989702]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/315726a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brewin, J., Horne, G., Chevassut, T.
|
|
<strong>Genomic landscapes and clonality of de novo AML. (Letter)</strong>
|
|
New Eng. J. Med. 369: 1472-1473, 2013.
|
|
|
|
|
|
[PubMed: 24106951]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMc1308782]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cancer Genome Atlas Research Network.
|
|
<strong>Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia.</strong>
|
|
New Eng. J. Med. 368: 2059-2074, 2013. Note: Erratum: New Eng. J. Med. 369: 98 only, 2013.
|
|
|
|
|
|
[PubMed: 23634996]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMoa1301689]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cirstea, I. C., Kutsche, K., Dvorsky, R., Gremer, L., Carta, C., Horn, D., Roberts, A. E., Lepri, F., Merbitz-Zahradnik, T., Konig, R., Kratz, C. P., Pantaleoni, F., and 19 others.
|
|
<strong>A restricted spectrum of NRAS mutations cause Noonan syndrome.</strong>
|
|
Nature. Genet. 42: 27-29, 2010.
|
|
|
|
|
|
[PubMed: 19966803]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng.497]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Davis, M., Malcolm, S., Hall, A., Marshall, C. J.
|
|
<strong>Localisation of the human N-ras oncogene to chromosome 1cen-p21 by in situ hybridisation.</strong>
|
|
EMBO J. 2: 2281-2283, 1983.
|
|
|
|
|
|
[PubMed: 6667677]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/j.1460-2075.1983.tb01735.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Davis, M., Malcolm, S., Hall, A.
|
|
<strong>The N-ras oncogene is located on the short arm of chromosome 1. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 37: 448-449, 1984.
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
De Filippi, P., Zecca, M., Lisini, D., Rosti, V., Cagioni, C., Carlo-Stella, C., Radi, O., Veggiotti, P., Mastronuzzi, A., Acquaviva, A., D'Ambrosio, A., Locatelli, F., Danesino, C.
|
|
<strong>Germ-line mutation of the NRAS gene may be responsible for the development of juvenile myelomonocytic leukaemia.</strong>
|
|
Brit. J. Haemat. 147: 706-709, 2009.
|
|
|
|
|
|
[PubMed: 19775298]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.2009.07894.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
de Martinville, B., Cunningham, J. M., Murray, M. J., Francke, U.
|
|
<strong>The N-ras oncogene assigned to chromosome 1 (p31-cen) by somatic cell hybrid analysis. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 37: 531 only, 1984.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Deka, R., Majumder, P. P., Warren, A. C., Surti, U., Hoffner, L., Hauselman, E., Antonarakis, S. E., Ferrell, R. E., Chakravarti, A.
|
|
<strong>Gene-centromere mapping using ovarian teratomas: results from chromosomes 1p, 13q and 21q. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 45 (suppl.): A137 only, 1989.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dessars, B., De Raeve, L. E., Morandini, R., Lefort, A., El Housni, H., Ghanem, G. E., Van den Eynde, B. J., Ma, W., Roseeuw, D., Vassart, G., Libert, F., Heimann, P.
|
|
<strong>Genotypic and gene expression studies in congenital melanocytic nevi: insight into initial steps of melanotumorigenesis.</strong>
|
|
J. Invest. Derm. 129: 139-147, 2009.
|
|
|
|
|
|
[PubMed: 18633438]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/jid.2008.203]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dracopoli, N. C., Meisler, M. H.
|
|
<strong>Mapping the human amylase gene cluster on the proximal short arm of chromosome 1 using a highly informative (CA)n repeat.</strong>
|
|
Genomics 7: 97-102, 1990.
|
|
|
|
|
|
[PubMed: 1692298]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(90)90523-w]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ekvall, S., Wilbe, M., Dahlgren, J., Legius, E., van Haeringen, A., Westphal, O., Anneren, G., Bondeson, M.-L.
|
|
<strong>Mutation in NRAS in familial Noonan syndrome: case report and review of the literature.</strong>
|
|
BMC Med. Genet. 16: 95, 2015. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 26467218]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1186/s12881-015-0239-1]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hafner, C., Toll, A., Gantner, S., Mauerer, A., Lurkin, I., Acquadro, F., Fernandez-Casado, A., Zwarthoff, E. C., Dietmaier, W., Baselga, E., Parera, E., Vicente, A., Casanova, A., Cigudosa, J., Mentzel, T., Pujol, R. M., Landthaler, M., Real, F. X.
|
|
<strong>Keratinocytic epidermal nevi are associated with mosaic RAS mutations.</strong>
|
|
J. Med. Genet. 49: 249-253, 2012.
|
|
|
|
|
|
[PubMed: 22499344]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmedgenet-2011-100637]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Haigis, K. M., Kendall, K. R., Wang, Y., Cheung, A., Haigis, M. C., Glickman, J. N., Niwa-Kawakita, M., Sweet-Cordero, A., Sebolt-Leopold, J., Shannon, K. M., Settleman, J., Giovannini, M., Jacks, T.
|
|
<strong>Differential effects of oncogenic K-Ras and N-Ras on proliferation, differentiation and tumor progression in the colon.</strong>
|
|
Nature Genet. 40: 600-608, 2008.
|
|
|
|
|
|
[PubMed: 18372904]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng.115]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hall, A., Brown, R.
|
|
<strong>Human N-ras: cDNA cloning and gene structure.</strong>
|
|
Nucleic Acids Res. 13: 5255-5268, 1985.
|
|
|
|
|
|
[PubMed: 2991860]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/nar/13.14.5255]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hall, A., Marshall, C. J., Spurr, N. K., Weiss, R. A.
|
|
<strong>Identification of transforming gene in two human sarcoma cell lines as a new member of the ras gene family located on chromosome 1.</strong>
|
|
Nature 303: 396-400, 1983.
|
|
|
|
|
|
[PubMed: 6304521]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/303396a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Johnson, S. M., Grosshans, H., Shingara, J., Byrom, M., Jarvis, R., Cheng, A., Labourier, E., Reinert, K. L., Brown, D., Slack, F. J.
|
|
<strong>RAS is regulated by the let-7 microRNA family.</strong>
|
|
Cell 120: 635-647, 2005.
|
|
|
|
|
|
[PubMed: 15766527]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.cell.2005.01.014]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kinsler, V. A., Thomas, A. C., Ishida, M., Bulstrode, N. W., Loughlin, S., Hing, S., Chalker, J., McKenzie, K., Abu-Amero, S., Slater, O., Chanudet, E., Palmer, R., Morrogh, D., Stanier, P., Healy, E., Sebire, N. J., Moore, G. E.
|
|
<strong>Multiple congenital melanocytic nevi and neurocutaneous melanosis are caused by postzygotic mutations in codon 61 of NRAS.</strong>
|
|
J. Invest. Derm. 133: 2229-2236, 2013. Note: Erratum: J. Invest. Derm. 136: 2326 only, 2016.
|
|
|
|
|
|
[PubMed: 23392294]
|
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[Full Text: https://doi.org/10.1038/jid.2013.70]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Li, Q., Bohin, N., Wen, T., Ng, V., Magee, J., Chen, S.-C., Shannon, K., Morrison, S. J.
|
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<strong>Oncogenic Nras has bimodal effects on stem cells that sustainably increase competitiveness.</strong>
|
|
Nature 504: 143-147, 2013.
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[PubMed: 24284627]
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[Full Text: https://doi.org/10.1038/nature12830]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Lim, Y. H., Ovejero, D., Sugarman, J. S., DeKlotz, C. M. C., Maruri, A., Eichenfield, L. F., Kelley, P. K., Juppner, H., Gottschalk, M., Tifft, C. J., Gafni, R. I., Boyce, A. M., and 12 others.
|
|
<strong>Multilineage somatic activating mutations in HRAS and NRAS cause mosaic cutaneous and skeletal lesions, elevated FGF23 and hypophosphatemia.</strong>
|
|
Hum. Molec. Genet. 23: 397-407, 2014.
|
|
|
|
|
|
[PubMed: 24006476]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddt429]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lin, D. T. S., Conibear, E.
|
|
<strong>ABHD17 proteins are novel protein depalmitoylases that regulate N-Ras palmitate turnover and subcellular localization.</strong>
|
|
eLife 4: e11306, 2015. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 26701913]
|
|
|
|
|
|
[Full Text: https://doi.org/10.7554/eLife.11306]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lubbert, M., Mirro, J., Jr., Miller, C. W., Kahan, J., Isaac, G., Kitchingman, G., Mertelsmann, R., Herrmann, F., McCormick, F., Koeffler, H. P.
|
|
<strong>N-ras gene point mutations in childhood acute lymphocytic leukemia correlate with a poor prognosis.</strong>
|
|
Blood 75: 1163-1169, 1990.
|
|
|
|
|
|
[PubMed: 2407301]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Marshall, C. J., Hall, A., Weiss, R. A.
|
|
<strong>A transforming gene present in human sarcoma cell lines.</strong>
|
|
Nature 299: 171-173, 1982.
|
|
|
|
|
|
[PubMed: 6287287]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/299171a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Matallanas, D., Arozarena, I., Berciano, M. T., Aaronson, D. S., Pellicer, A., Lafarga, M., Crespo, P.
|
|
<strong>Differences on the inhibitory specificities of H-Ras, K-Ras, and N-Ras (N17) dominant negative mutants are related to their membrane microlocalization.</strong>
|
|
J. Biol. Chem. 278: 4572-4581, 2003.
|
|
|
|
|
|
[PubMed: 12458225]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M209807200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Matsuda, K., Shimada, A., Yoshida, N., Ogawa, A., Watanabe, A., Yajima, S., Iizuka, S., Koike, K., Yanai, F., Kawasaki, K., Yanagimachi, M., Kikuchi, A., and 10 others.
|
|
<strong>Spontaneous improvement of hematologic abnormalities in patients having juvenile myelomonocytic leukemia with specific RAS mutations.</strong>
|
|
Blood 109: 5477-5480, 2007.
|
|
|
|
|
|
[PubMed: 17332249]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2006-09-046649]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Miller, C. A., Wilson, R. K., Ley, T. J.
|
|
<strong>Reply to Brewin et al. (Letter)</strong>
|
|
New Eng. J. Med. 369: 1473 only, 2013.
|
|
|
|
|
|
[PubMed: 24106950]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMc1308782]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mitchell, E. L. D., Jones, D., White, G. R. M., Varley, J. M., Santibanez Koref, M. F.
|
|
<strong>Determination of the gene order of the three loci CD2, NGFB, and NRAS at human chromosome band 1p13 and refinement of their localisation at the subband level by fluorescence in situ hybridization.</strong>
|
|
Cytogenet. Cell Genet. 70: 183-185, 1995. Note: Erratum: Cytogenet Cell Genet. 71: 306 only, 1995.
|
|
|
|
|
|
[PubMed: 7789166]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000134028]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Munke, M., Lindgren, V., de Martinville, B., Francke, U.
|
|
<strong>Comparative analysis of mouse-human hybrids with rearranged chromosomes 1 by in situ hybridization and Southern blotting: high-resolution mapping of NRAS, NGFB, and AMY on human chromosome 1.</strong>
|
|
Somat. Cell Molec. Genet. 10: 589-599, 1984.
|
|
|
|
|
|
[PubMed: 6209808]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF01535224]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nazarian, R., Shi, H., Wang, Q., Kong, X., Koya, R. C., Lee, H., Chen, Z., Lee, M.-K., Attar, N., Sazegar, H., Chodon, T., Nelson, S. F., McArthur, G., Sosman, J. A., Ribas, A., Lo, R. S.
|
|
<strong>Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation.</strong>
|
|
Nature 468: 973-977, 2010.
|
|
|
|
|
|
[PubMed: 21107323]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature09626]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Niemela, J. E., Lu, L., Fleisher, T. A., Davis, J., Caminha, I., Natter, M., Beer, L. A., Dowdell, K. C., Pittaluga, S., Raffeld, M., Rao, V. K., Oliveira, J. B.
|
|
<strong>Somatic KRAS mutations associated with a human nonmalignant syndrome of autoimmunity and abnormal leukocyte homeostasis.</strong>
|
|
Blood 117: 2883-2886, 2010.
|
|
|
|
|
|
[PubMed: 21079152]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2010-07-295501]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nikiforova, M. N., Lynch, R. A., Biddinger, P. W., Alexander, E. K., Dorn, G. W., II, Tallini, G., Kroll, T. G., Nikiforov, Y. E.
|
|
<strong>RAS point mutations and PAX8-PPAR-gamma rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma.</strong>
|
|
J. Clin. Endocr. Metab. 88: 2318-2326, 2003.
|
|
|
|
|
|
[PubMed: 12727991]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2002-021907]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nitta, N., Ochiai, M., Nagao, M., Sugimura, T.
|
|
<strong>Amino-acid substitution at codon 13 of the N-ras oncogene in rectal cancer in a Japanese patient.</strong>
|
|
Jpn. J. Cancer Res. 78: 21-26, 1987.
|
|
|
|
|
|
[PubMed: 3102434]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Oliveira, J. B., Bidere, N., Niemela, J. E., Zheng, L., Sakai, K., Nix, C. P., Danner, R. L., Barb, J., Munson, P. J., Puck, J. M., Dale, J., Straus, S. E., Fleisher, T. A., Lenardo, M. J.
|
|
<strong>NRAS mutation causes a human autoimmune lymphoproliferative syndrome.</strong>
|
|
Proc. Nat. Acad. Sci. 104: 8953-8958, 2007.
|
|
|
|
|
|
[PubMed: 17517660]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0702975104]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Popescu, N. C., Amsbaugh, S. C., DiPaolo, J. A., Tronick, S. R., Aaronson, S. A., Swan, D. C.
|
|
<strong>Chromosomal localization of three human ras genes by in situ molecular hybridization.</strong>
|
|
Somat. Cell Molec. Genet. 11: 149-155, 1985.
|
|
|
|
|
|
[PubMed: 3856955]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF01534703]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Povey, S., Morton, N. E., Sherman, S. L.
|
|
<strong>Report of the committee on the genetic constitution of chromosomes 1 and 2 (HGM8).</strong>
|
|
Cytogenet. Cell Genet. 40: 67-106, 1985.
|
|
|
|
|
|
[PubMed: 3864603]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000132170]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rabin, M., Watson, M., Barker, P. E., Ryan, J., Breg, W. R., Ruddle, F. H.
|
|
<strong>NRAS transforming gene maps to region p11-p13 on chromosome 1 by in situ hybridization.</strong>
|
|
Cytogenet. Cell Genet. 38: 70-72, 1984.
|
|
|
|
|
|
[PubMed: 6705568]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000132032]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rabin, M., Watson, M., Barker, P., Ryan, J., Breg, W. R., Ruddle, F. H.
|
|
<strong>Chromosomal assignment of human c-fos and N-ras oncogenes. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 35: 148A only, 1983.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rocks, O., Peyker, A., Kahms, M., Verveer, P. J., Koerner, C., Lumbierres, M., Kuhlmann, J., Waldmann, H., Wittinghofer, A., Bastiaens, P. I. H.
|
|
<strong>An acylation cycle regulates localization and activity of palmitoylated Ras isoforms.</strong>
|
|
Science 307: 1746-1752, 2005.
|
|
|
|
|
|
[PubMed: 15705808]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1105654]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ryan, J., Barker, P. E., Shimizu, K., Wigler, M., Ruddle, F. H.
|
|
<strong>Chromosomal assignment of a family of human oncogenes.</strong>
|
|
Proc. Nat. Acad. Sci. 80: 4460-4463, 1983.
|
|
|
|
|
|
[PubMed: 6576347]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.80.14.4460]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Takahashi, C., Contreras, B., Iwanaga, T., Takegami, Y., Bakker, A., Bronson, R. T., Noda, M., Loda, M., Hunt, J. L., Ewen, M. E.
|
|
<strong>Nras loss induces metastatic conversion of Rb1-deficient neuroendocrine thyroid tumor.</strong>
|
|
Nature Genet. 38: 118-123, 2006.
|
|
|
|
|
|
[PubMed: 16369533]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1703]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Taparowsky, E., Shimizu, K., Goldfarb, M., Wigler, M.
|
|
<strong>Structure and activation of the human N-ras gene.</strong>
|
|
Cell 34: 581-586, 1983.
|
|
|
|
|
|
[PubMed: 6616621]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0092-8674(83)90390-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vasko, V., Ferrand, M., Di Cristofaro, J., Carayon, P., Henry, J. F., De Micco, C.
|
|
<strong>Specific pattern of RAS oncogene mutations in follicular thyroid tumors.</strong>
|
|
J. Clin. Endocr. Metab. 88: 2745-2752, 2003.
|
|
|
|
|
|
[PubMed: 12788883]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2002-021186]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yuasa, Y., Gol, R. A., Chang, A., Chiu, I.-M., Reddy, E. P., Tronick, S. R., Aaronson, S. A.
|
|
<strong>Mechanism of activation of an N-ras oncogene of SW-1271 human lung carcinoma cells.</strong>
|
|
Proc. Nat. Acad. Sci. 81: 3670-3674, 1984.
|
|
|
|
|
|
[PubMed: 6587382]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.81.12.3670]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
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|
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|
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OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
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