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Entry
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- *609591 - RIC-LIKE PROTEIN WITHOUT CAAX MOTIF 1; RIT1
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- OMIM
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<p>
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<span class="h4">*609591</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/609591">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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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 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=ENSG00000143622;t=ENST00000368323" 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=6016" 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=609591" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</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=ENSG00000143622;t=ENST00000368323" 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_001256820,NM_001256821,NM_006912" 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_006912" 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=609591" 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=10195&isoform_id=10195_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/RIT1" 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/1656001,1702928,2286101,4234918,5902050,20147739,38258628,47115215,74353760,74355775,119573409,189054382,194384996,378744212,378744214" 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/Q92963" 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=6016" 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=ENSG00000143622;t=ENST00000368323" 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=RIT1" 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=RIT1" 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+6016" 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/RIT1" 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:6016" 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/6016" 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=ENST00000368323.8&hgg_start=155897808&hgg_end=155911349&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:10023" 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/rit1" 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=609591[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 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=609591[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/RIT1/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/ENSG00000143622" 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=RIT1" 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=RIT1" 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=RIT1" 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=RIT1&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/PA35528" 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:10023" 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/FBgn0265605.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:108053" 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/RIT1#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:108053" 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/6016/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=6016" 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://zfin.org/ZDB-GENE-070912-329" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://reactome.org/content/query?q=RIT1&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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609591
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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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RIC-LIKE PROTEIN WITHOUT CAAX MOTIF 1; RIT1
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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RAS-LIKE PROTEIN EXPRESSED IN MANY TISSUES; RIT<br />
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ROC1
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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=RIT1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">RIT1</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
|
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Cytogenetic location: <a href="/geneMap/1/1231?start=-3&limit=10&highlight=1231">1q22</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr1:155897808-155911349&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'})">1:155,897,808-155,911,349</a> </span>
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</em>
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</strong>
|
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="geneMap" class="mim-anchor"></a>
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<div style="margin-bottom: 10px;">
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<span class="h4 mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
|
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<span class="mim-font">
|
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<a href="/geneMap/1/1231?start=-3&limit=10&highlight=1231">
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1q22
|
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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Noonan syndrome 8
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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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<a href="/entry/615355"> 615355 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
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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/609591" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
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<li><a href="/graph/radial/609591" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
|
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</span>
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</span>
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</h4>
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<div>
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<a id="description" class="mim-anchor"></a>
|
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
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<span class="mim-font">
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<strong>Description</strong>
|
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</span>
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</h4>
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</div>
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<p>RIT belongs to the RAS (HRAS; <a href="/entry/190020">190020</a>) subfamily of small GTPases (<a href="#6" class="mim-tip-reference" title="Hynds, D. L., Spencer, M. L., Andres, D. A., Snow, D. M. <strong>Rit promotes MEK-independent neurite branching in human neuroblastoma cells.</strong> J. Cell Sci. 116: 1925-1935, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12668729/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12668729</a>] [<a href="https://doi.org/10.1242/jcs.00401" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12668729">Hynds et al., 2003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12668729" 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>By PCR using degenerate primers based on the conserved G3 and G4 domains of RAS, followed by screening a mouse retina cDNA library, <a href="#8" class="mim-tip-reference" title="Lee, C.-H. J., Della, N. G., Chew, C. E., Zack, D. J. <strong>Rin, a neuron-specific and calmodulin-binding small G-protein, and Rit define a novel subfamily of Ras proteins.</strong> J. Neurosci. 16: 6784-6794, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8824319/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8824319</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=8824319[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/10.1523/JNEUROSCI.16-21-06784.1996" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8824319">Lee et al. (1996)</a> cloned mouse Rit. The deduced 219-amino acid protein has a calculated molecular mass of 25.6 kD. By EST database analysis, <a href="#8" class="mim-tip-reference" title="Lee, C.-H. J., Della, N. G., Chew, C. E., Zack, D. J. <strong>Rin, a neuron-specific and calmodulin-binding small G-protein, and Rit define a novel subfamily of Ras proteins.</strong> J. Neurosci. 16: 6784-6794, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8824319/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8824319</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=8824319[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/10.1523/JNEUROSCI.16-21-06784.1996" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8824319">Lee et al. (1996)</a> identified human RIT. The deduced human protein contains 219 amino acids and shares 94% identity with mouse Rit. Human and mouse RIT have 5 highly conserved domains characteristic of small G proteins, but they lack the C-terminal CAAX prenylation motif found in several other RAS-like proteins. Northern blot analysis detected a 1.2-kb transcript in all mouse tissues examined. Epitope-tagged mouse Rit localized to the plasma membrane of transfected cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8824319" 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 searching an EST database for sequences similar to Drosophila Ric, <a href="#11" class="mim-tip-reference" title="Wes, P. D., Yu, M., Montell, C. <strong>RIC, a calmodulin-binding Ras-like GTPase.</strong> EMBO J. 15: 5839-5848, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8918462/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8918462</a>]" pmid="8918462">Wes et al. (1996)</a> identified human RIT and RIN (<a href="/entry/609592">609592</a>). The core GTPase domain of RIT shares 76% identity with that of RIN, and there is only 1 conservative substitution between the 2 human proteins and Drosophila Ric within the effector G2 region. Northern blot analysis detected RIT transcripts of 1.35, 2.9, and 3.9 kb in most tissues examined. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8918462" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#8" class="mim-tip-reference" title="Lee, C.-H. J., Della, N. G., Chew, C. E., Zack, D. J. <strong>Rin, a neuron-specific and calmodulin-binding small G-protein, and Rit define a novel subfamily of Ras proteins.</strong> J. Neurosci. 16: 6784-6794, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8824319/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8824319</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=8824319[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/10.1523/JNEUROSCI.16-21-06784.1996" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8824319">Lee et al. (1996)</a> demonstrated that mouse Rit bound radiolabeled GTP. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8824319" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Shao, H., Kadono-Okuda, K., Finlin, B. S., Andres, D. A. <strong>Biochemical characterization of the Ras-related GTPases Rit and Rin.</strong> Arch. Biochem. Biophys. 371: 207-219, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10545207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10545207</a>] [<a href="https://doi.org/10.1006/abbi.1999.1448" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10545207">Shao et al. (1999)</a> demonstrated that recombinant human RIT and RIN bound GTP and exhibited intrinsic GTPase activity. Conversion of gln79 to leu in RIT resulted in complete loss of GTPase activity. The activity of RIT and RIN was significantly different from that of the majority of RAS-related GTPases, and the GTP dissociation rates were 5- to 10-fold faster than most RAS-like GTPases. Yeast 2-hybrid analysis showed that RIT and RIN interacted with the RAS-binding proteins RALGDS (<a href="/entry/601619">601619</a>), RLF (<a href="/entry/180610">180610</a>), and AF6 (MLLT4; <a href="/entry/159559">159559</a>), but not with RAF kinases (e.g., RAF1; <a href="/entry/164760">164760</a>), RIN1 (<a href="/entry/605965">605965</a>), or the p110 subunit of PI3K (see <a href="/entry/171834">171834</a>). <a href="#9" class="mim-tip-reference" title="Shao, H., Kadono-Okuda, K., Finlin, B. S., Andres, D. A. <strong>Biochemical characterization of the Ras-related GTPases Rit and Rin.</strong> Arch. Biochem. Biophys. 371: 207-219, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10545207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10545207</a>] [<a href="https://doi.org/10.1006/abbi.1999.1448" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10545207">Shao et al. (1999)</a> concluded that RIT and RIN regulate signaling pathways and cellular processes distinct from those controlled by RAS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10545207" 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 expression of RIT in a human neuroblastoma cell line, <a href="#6" class="mim-tip-reference" title="Hynds, D. L., Spencer, M. L., Andres, D. A., Snow, D. M. <strong>Rit promotes MEK-independent neurite branching in human neuroblastoma cells.</strong> J. Cell Sci. 116: 1925-1935, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12668729/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12668729</a>] [<a href="https://doi.org/10.1242/jcs.00401" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12668729">Hynds et al. (2003)</a> demonstrated that RIT increased neurite outgrowth and branching through MEK (see MEK1; <a href="/entry/176872">176872</a>)-dependent and MEK-independent signaling mechanisms, respectively. Adenoviral expression of wildtype or constitutively active RIT increased neurite initiation, elongation, and branching on endogenous matrix or a purified laminin-1 substratum. This outgrowth was morphologically distinct from that promoted by constitutively active RAS or RAF. Constitutively active RIT increased phosphorylation of ERK1 (MAPK3; <a href="/entry/601795">601795</a>)/ERK2 (MAPK1; <a href="/entry/176948">176948</a>), but not AKT (see AKT1; <a href="/entry/164730">164730</a>). A MEK inhibitor blocked RIT-induced neurite initiation, but not elongation or branching. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12668729" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Shi, G.-X., Andres, D. A. <strong>Rit contributes to nerve growth factor-induced neuronal differentiation via activation of B-Raf-extracellular signal-regulated kinase and p38 mitogen-activated protein kinase cascades.</strong> Molec. Cell. Biol. 25: 830-846, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15632082/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15632082</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15632082[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/10.1128/MCB.25.2.830-846.2005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15632082">Shi and Andres (2005)</a> found that stimulation of a rat pheochromocytoma cell line by growth factors, including nerve growth factor (NGF; <a href="/entry/162030">162030</a>), resulted in rapid and prolonged Rit activation. Ectopic expression of active human RIT promoted neurite outgrowth and stimulated activation of both Erk and p38 MAP kinase (MAPK14; <a href="/entry/600289">600289</a>) signaling pathways. RIT-induced differentiation depended upon both MAP kinase cascades, since MEK inhibition blocked RIT-induced neurite outgrowth, and p38 blockade inhibited neurite elongation and branching, but not neurite initiation. Moreover, the ability of NGF to promote neuronal differentiation was attenuated by Rit knockdown. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15632082" 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="#5" class="mim-tip-reference" title="Heo, W. D., Inoue, T., Park, W. S., Kim, M. L., Park, B. O., Wandless, T. J., Meyer, T. <strong>PI(3,4,5)P(3) and PI(4,5)P(2) lipids target proteins with polybasic clusters to the plasma membrane.</strong> Science 314: 1458-1461, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17095657/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17095657</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17095657[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1134389" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17095657">Heo et al. (2006)</a> surveyed plasma membrane targeting mechanisms by imaging the subcellular localization of 125 fluorescent protein-conjugated Ras, Rab, Arf, and Rho proteins. Of 48 proteins that were localized to the plasma membrane, 37 contained clusters of positively charged amino acids. To test whether these polybasic clusters bind negatively charged phosphatidylinositol 4,5-bisphosphate lipids, <a href="#5" class="mim-tip-reference" title="Heo, W. D., Inoue, T., Park, W. S., Kim, M. L., Park, B. O., Wandless, T. J., Meyer, T. <strong>PI(3,4,5)P(3) and PI(4,5)P(2) lipids target proteins with polybasic clusters to the plasma membrane.</strong> Science 314: 1458-1461, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17095657/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17095657</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17095657[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1134389" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17095657">Heo et al. (2006)</a> developed a chemical phosphatase activation method to deplete plasma membrane phosphatidylinositol 4,5-bisphosphate. Unexpectedly, proteins with polybasic clusters dissociated from the plasma membrane only when both phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate were depleted, arguing that both lipid second messengers jointly regulate plasma membrane targeting. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17095657" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#11" class="mim-tip-reference" title="Wes, P. D., Yu, M., Montell, C. <strong>RIC, a calmodulin-binding Ras-like GTPase.</strong> EMBO J. 15: 5839-5848, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8918462/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8918462</a>]" pmid="8918462">Wes et al. (1996)</a> stated that the RIT gene was mapped to chromosome 1 by somatic cell hybrid analysis. The mouse Rit gene maps to chromosome 3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8918462" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In 17 unrelated patients with Noonan syndrome-8 (NS8; <a href="/entry/615355">615355</a>), <a href="#1" class="mim-tip-reference" title="Aoki, Y., Niihori, T., Banjo, T., Okamoto, N., Mizuno, S., Kurosawa, K., Ogata, T., Takada, F., Yano, M., Ando, T., Hoshika, T., Barnett, C., and 13 others. <strong>Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK pathway syndrome.</strong> Am. J. Hum. Genet. 93: 173-180, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23791108/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23791108</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23791108[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2013.05.021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23791108">Aoki et al. (2013)</a> identified heterozygous mutations in the RIT1 gene (see, e.g., <a href="#0001">609591.0001</a>-<a href="#0004">609591.0004</a>). The first mutations were found by exome sequencing and subsequent mutations were identified from a larger cohort of patients screened for the RIT1 gene. A total of 9 missense mutations were found in 17 (9%) of 180 individuals suspected to have the disorder. The phenotype was characterized by short stature, distinctive facial features, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. A subset of patients showed intellectual disabilities. All of the mutations occurred de novo, except in 1 patient who inherited the mutation from a mother with a Noonan syndrome phenotype. The mutations tended to cluster in the switch II region, and in vitro functional expression studies of 3 of the mutations showed that they resulted in a gain of function. Transfection of 2 of the mutations into zebrafish embryos resulted in a variety of developmental defects, including gastrulation defects, craniofacial abnormalities, pericardial edema, and elongated yolk sac. A smaller percentage of mutant embryos showed even more disorganized growth and abnormal cardiogenesis. The findings were similar to those observed with mutations in other RAS genes (see, e.g., PTPN11, <a href="/entry/176876">176876</a>; SOS1, <a href="/entry/182530">182530</a>; NRAS, <a href="/entry/164790">164790</a>) causing other forms of Noonan syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23791108" 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 6 Brazilian patients with Noonan syndrome but without mutation in selected exons of any known Noonan syndrome-causing genes, <a href="#2" class="mim-tip-reference" title="Bertola, D. R., Yamamoto, G. L., Almeida, T. F., Buscarilli, M., Jorge, A. A. L., Malaquias, A. C., Kim, C. A., Takahashi, V. N. V., Passos-Bueno, M. R., Pereira, A. C. <strong>Further evidence of the importance of RIT1 in Noonan syndrome.</strong> Am. J. Med. Genet. 164A: 2952-2957, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25124994/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25124994</a>] [<a href="https://doi.org/10.1002/ajmg.a.36722" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25124994">Bertola et al. (2014)</a> identified 4 heterozygous missense mutations in the RIT1 gene, all of which had previously been identified in patients with NS8 by <a href="#1" class="mim-tip-reference" title="Aoki, Y., Niihori, T., Banjo, T., Okamoto, N., Mizuno, S., Kurosawa, K., Ogata, T., Takada, F., Yano, M., Ando, T., Hoshika, T., Barnett, C., and 13 others. <strong>Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK pathway syndrome.</strong> Am. J. Hum. Genet. 93: 173-180, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23791108/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23791108</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23791108[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2013.05.021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23791108">Aoki et al. (2013)</a>. The mutations were identified by exome sequencing. Parental DNA, which was available for only 2 patients, showed that the mutations were probably de novo. The affected patients had a high frequency of high birthweight, relative macrocephaly, left ventricular hypertrophy, and ectodermal findings such as curly hair, hyperpigmentation, and wrinkled palms and soles. There was no apparent intellectual disability, but formal testing was not performed. Other findings were similar to those observed with mutations in genes causing different forms of Noonan syndrome. <a href="#2" class="mim-tip-reference" title="Bertola, D. R., Yamamoto, G. L., Almeida, T. F., Buscarilli, M., Jorge, A. A. L., Malaquias, A. C., Kim, C. A., Takahashi, V. N. V., Passos-Bueno, M. R., Pereira, A. C. <strong>Further evidence of the importance of RIT1 in Noonan syndrome.</strong> Am. J. Med. Genet. 164A: 2952-2957, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25124994/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25124994</a>] [<a href="https://doi.org/10.1002/ajmg.a.36722" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25124994">Bertola et al. (2014)</a> suggested possible hotspots at residues 57 and 95 of the protein due to recurrent mutations, and recommended that RIT1 be added to gene panels for the molecular diagnosis of Noonan syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=25124994+23791108" 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 4 unrelated Polish girls with NS8, <a href="#4" class="mim-tip-reference" title="Gos, M., Fahiminiya, S., Poznanski, J., Klapecki, J., Obersztyn, E., Piotrowicz, M., Wierzba, J., Posmyk, R., Bal, J., Majewski, J. <strong>Contribution of RIT1 mutations to the pathogenesis of Noonan syndrome: four new cases and further evidence of heterogeneity.</strong> Am. J. Med. Genet. 164A: 2310-2316, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24939608/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24939608</a>] [<a href="https://doi.org/10.1002/ajmg.a.36646" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24939608">Gos et al. (2014)</a> identified 3 different heterozygous missense mutations in the RIT1 gene (<a href="#0004">609591.0004</a>-<a href="#0006">609591.0006</a>). The mutations in the first 2 patients were found by whole-exome sequencing after mutations in common Noonan syndrome genes were excluded. The mutations in the second 2 patients were found by direct sequencing of the RIT1 gene in 64 patients with Noonan syndrome. Functional studies of the variants were not performed. The RIT1 mutation rate in this study was estimated at 3.8% (4 of 106 NS patients). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24939608" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Kouz, K., Lissewski, C., Spranger, S., Mitter, D., Riess, A., Lopez-Gonzalez, V., Luttgen, S., Aydin, H., von Deimling, F., Evers, C., Hahn, A., Hempel, M., and 14 others. <strong>Genotype and phenotype in patients with Noonan syndrome and a RIT1 mutation.</strong> Genet. Med. 18: 1226-1234, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27101134/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27101134</a>] [<a href="https://doi.org/10.1038/gim.2016.32" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27101134">Kouz et al. (2016)</a> sequenced RIT1 in 310 mutation-negative individuals with a suspected RASopathy and prospectively in individuals who underwent genetic testing for NS. Eleven different RIT1 missense mutations, 3 of which were novel, were identified in 33 subjects from 28 families; codons 57, 82, and 95 represent mutation hotspots. RIT1 is 1 of the 4 most common genes mutated in Noonan syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27101134" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#3" class="mim-tip-reference" title="Castel, P., Cheng, A., Cuevas-Navarro, A., Everman, D. B., Papageorge, A. G., Simanshu, D. K., Tankka, A., Galeas, J., Urisman, A., McCormick, F. <strong>RIT1 oncoproteins escape LZTR1-mediated proteolysis.</strong> Science 363: 1226-1230, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30872527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30872527</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30872527[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.aav1444" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30872527">Castel et al. (2019)</a> used an isogenic germline knockin mouse model to study the effects of RIT1 mutation at the organismal level, which resulted in a phenotype resembling Noonan syndrome. By mass spectrometry, <a href="#3" class="mim-tip-reference" title="Castel, P., Cheng, A., Cuevas-Navarro, A., Everman, D. B., Papageorge, A. G., Simanshu, D. K., Tankka, A., Galeas, J., Urisman, A., McCormick, F. <strong>RIT1 oncoproteins escape LZTR1-mediated proteolysis.</strong> Science 363: 1226-1230, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30872527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30872527</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30872527[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.aav1444" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30872527">Castel et al. (2019)</a> detected a RIT1 interactor, LZTR1 (<a href="/entry/600574">600574</a>), that acts as an adaptor for protein degradation. Pathogenic mutations affecting either RIT1 or LZTR1 resulted in incomplete degradation of RIT1. This led to RIT1 accumulation and dysregulated growth factor signaling responses. <a href="#3" class="mim-tip-reference" title="Castel, P., Cheng, A., Cuevas-Navarro, A., Everman, D. B., Papageorge, A. G., Simanshu, D. K., Tankka, A., Galeas, J., Urisman, A., McCormick, F. <strong>RIT1 oncoproteins escape LZTR1-mediated proteolysis.</strong> Science 363: 1226-1230, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30872527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30872527</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30872527[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.aav1444" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30872527">Castel et al. (2019)</a> concluded that their results highlighted a mechanism of pathogenesis that relies on impaired protein degradation of the Ras GTPase RIT1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30872527" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000054404 OR RCV000159100 OR RCV000207349 OR RCV000856747 OR RCV001731346 OR RCV001813373 OR RCV002399414 OR RCV003390753" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000054404, RCV000159100, RCV000207349, RCV000856747, RCV001731346, RCV001813373, RCV002399414, RCV003390753" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000054404...</a>
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<p>In 4 unrelated patients with Noonan syndrome-8 (NS8; <a href="/entry/615355">615355</a>), <a href="#1" class="mim-tip-reference" title="Aoki, Y., Niihori, T., Banjo, T., Okamoto, N., Mizuno, S., Kurosawa, K., Ogata, T., Takada, F., Yano, M., Ando, T., Hoshika, T., Barnett, C., and 13 others. <strong>Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK pathway syndrome.</strong> Am. J. Hum. Genet. 93: 173-180, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23791108/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23791108</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23791108[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2013.05.021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23791108">Aoki et al. (2013)</a> identified a de novo heterozygous c.170C-G transversion in exon 4 of the RIT1 gene, resulting in an ala57-to-gly (A57G) substitution at a conserved residue. In vitro cellular expression studies showed that the A57G mutation resulted in a gain of function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23791108" 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 2 unrelated Brazilian patients with NS8, <a href="#2" class="mim-tip-reference" title="Bertola, D. R., Yamamoto, G. L., Almeida, T. F., Buscarilli, M., Jorge, A. A. L., Malaquias, A. C., Kim, C. A., Takahashi, V. N. V., Passos-Bueno, M. R., Pereira, A. C. <strong>Further evidence of the importance of RIT1 in Noonan syndrome.</strong> Am. J. Med. Genet. 164A: 2952-2957, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25124994/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25124994</a>] [<a href="https://doi.org/10.1002/ajmg.a.36722" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25124994">Bertola et al. (2014)</a> identified heterozygosity for the A57G mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25124994" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000054405 OR RCV000207350 OR RCV000255048 OR RCV000508083 OR RCV001174556 OR RCV001265779 OR RCV001813418 OR RCV004745234" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000054405, RCV000207350, RCV000255048, RCV000508083, RCV001174556, RCV001265779, RCV001813418, RCV004745234" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000054405...</a>
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<p>In a patient with Noonan syndrome-8 (NS8; <a href="/entry/615355">615355</a>), <a href="#1" class="mim-tip-reference" title="Aoki, Y., Niihori, T., Banjo, T., Okamoto, N., Mizuno, S., Kurosawa, K., Ogata, T., Takada, F., Yano, M., Ando, T., Hoshika, T., Barnett, C., and 13 others. <strong>Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK pathway syndrome.</strong> Am. J. Hum. Genet. 93: 173-180, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23791108/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23791108</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23791108[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2013.05.021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23791108">Aoki et al. (2013)</a> identified a de novo heterozygous c.242A-G transition in exon 5 of the RIT1 gene, resulting in a glu81-to-gly (E81G) substitution at a conserved residue. In vitro cellular expression studies showed that the E81G mutation resulted in a gain of function. Transfection of the E81G mutation into zebrafish embryos resulted in a variety of developmental defects, including gastrulation defects, craniofacial abnormalities, pericardial edema, and elongated yolk sac. A smaller percentage of mutant embryos showed even more disorganized growth and abnormal cardiogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23791108" 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> rs730881014 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs730881014;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/rs730881014?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=rs730881014" 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=rs730881014" 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=RCV000054406 OR RCV000159101 OR RCV000207343 OR RCV001255602 OR RCV001375970 OR RCV001813414 OR RCV003398818 OR RCV003483526" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000054406, RCV000159101, RCV000207343, RCV001255602, RCV001375970, RCV001813414, RCV003398818, RCV003483526" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000054406...</a>
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<p>In 2 unrelated patients with Noonan syndrome-8 (NS8; <a href="/entry/615355">615355</a>), <a href="#1" class="mim-tip-reference" title="Aoki, Y., Niihori, T., Banjo, T., Okamoto, N., Mizuno, S., Kurosawa, K., Ogata, T., Takada, F., Yano, M., Ando, T., Hoshika, T., Barnett, C., and 13 others. <strong>Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK pathway syndrome.</strong> Am. J. Hum. Genet. 93: 173-180, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23791108/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23791108</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23791108[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2013.05.021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23791108">Aoki et al. (2013)</a> identified a de novo heterozygous c.246T-G transversion in exon 5 of the RIT1 gene, resulting in a phe82-to-leu (F82L) substitution at a conserved residue. The mutation, which was initially found by exome sequencing, was not present in several control databases. In vitro cellular expression studies showed that the F82L mutation resulted in a gain of function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23791108" 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">rs672601335 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs672601335;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=rs672601335" 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=rs672601335" 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=RCV000054407 OR RCV000207348 OR RCV000298790 OR RCV001192384 OR RCV001813374 OR RCV002433549 OR RCV003450918 OR RCV003915017" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000054407, RCV000207348, RCV000298790, RCV001192384, RCV001813374, RCV002433549, RCV003450918, RCV003915017" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000054407...</a>
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<p>In 4 unrelated patients with Noonan syndrome-8 (NS8; <a href="/entry/615355">615355</a>), <a href="#1" class="mim-tip-reference" title="Aoki, Y., Niihori, T., Banjo, T., Okamoto, N., Mizuno, S., Kurosawa, K., Ogata, T., Takada, F., Yano, M., Ando, T., Hoshika, T., Barnett, C., and 13 others. <strong>Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK pathway syndrome.</strong> Am. J. Hum. Genet. 93: 173-180, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23791108/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23791108</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23791108[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2013.05.021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23791108">Aoki et al. (2013)</a> identified a de novo heterozygous c.284G-C transversion in exon 5 of the RIT1 gene, resulting in a gly95-to-ala (G95A) substitution. The mutation, which was initially found by exome sequencing, was not present in several control databases. In vitro cellular expression studies showed that the G95A mutation resulted in a gain of function. Transfection of the G95A mutation into zebrafish embryos resulted in a variety of developmental defects, including gastrulation defects, craniofacial abnormalities, pericardial edema, and elongated yolk sac. A smaller percentage of mutant embryos showed even more disorganized growth and abnormal cardiogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23791108" 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 2 unrelated Brazilian patients with NS8, <a href="#2" class="mim-tip-reference" title="Bertola, D. R., Yamamoto, G. L., Almeida, T. F., Buscarilli, M., Jorge, A. A. L., Malaquias, A. C., Kim, C. A., Takahashi, V. N. V., Passos-Bueno, M. R., Pereira, A. C. <strong>Further evidence of the importance of RIT1 in Noonan syndrome.</strong> Am. J. Med. Genet. 164A: 2952-2957, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25124994/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25124994</a>] [<a href="https://doi.org/10.1002/ajmg.a.36722" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25124994">Bertola et al. (2014)</a> identified heterozygosity for the G95A mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25124994" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Gos, M., Fahiminiya, S., Poznanski, J., Klapecki, J., Obersztyn, E., Piotrowicz, M., Wierzba, J., Posmyk, R., Bal, J., Majewski, J. <strong>Contribution of RIT1 mutations to the pathogenesis of Noonan syndrome: four new cases and further evidence of heterogeneity.</strong> Am. J. Med. Genet. 164A: 2310-2316, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24939608/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24939608</a>] [<a href="https://doi.org/10.1002/ajmg.a.36646" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24939608">Gos et al. (2014)</a> identified a heterozygous G95A mutation in 2 unrelated Polish girls with NS8. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24939608" 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">rs869025194 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs869025194;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=rs869025194" 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=rs869025194" 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=RCV000170492 OR RCV000207352 OR RCV000263369 OR RCV001778757 OR RCV001813420 OR RCV002453562" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000170492, RCV000207352, RCV000263369, RCV001778757, RCV001813420, RCV002453562" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000170492...</a>
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<p>In a 6-year-old Polish girl with Noonan syndrome-8 (NS8; <a href="/entry/615355">615355</a>), <a href="#4" class="mim-tip-reference" title="Gos, M., Fahiminiya, S., Poznanski, J., Klapecki, J., Obersztyn, E., Piotrowicz, M., Wierzba, J., Posmyk, R., Bal, J., Majewski, J. <strong>Contribution of RIT1 mutations to the pathogenesis of Noonan syndrome: four new cases and further evidence of heterogeneity.</strong> Am. J. Med. Genet. 164A: 2310-2316, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24939608/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24939608</a>] [<a href="https://doi.org/10.1002/ajmg.a.36646" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24939608">Gos et al. (2014)</a> identified a de novo heterozygous c.244T-G transversion (c.244T-G, NM_006912) in the RIT1 gene, resulting in a phe82-to-val (F82V) substitution at a highly conserved residue in the GTPase domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the dbSNP, 1000 Genomes Project, or Exome Variant Server databases. Functional studies of the variant were not performed. A different mutation at the same codon has been reported (F82L; <a href="#0003">609591.0003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24939608" 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">rs483352822 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs483352822;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=rs483352822" 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=rs483352822" 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=RCV000170493 OR RCV000355969 OR RCV001813422 OR RCV003416059 OR RCV004020021" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000170493, RCV000355969, RCV001813422, RCV003416059, RCV004020021" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000170493...</a>
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<p>In a 5.5-year-old Polish girl with Noonan syndrome-8 (NS8; <a href="/entry/615355">615355</a>), <a href="#4" class="mim-tip-reference" title="Gos, M., Fahiminiya, S., Poznanski, J., Klapecki, J., Obersztyn, E., Piotrowicz, M., Wierzba, J., Posmyk, R., Bal, J., Majewski, J. <strong>Contribution of RIT1 mutations to the pathogenesis of Noonan syndrome: four new cases and further evidence of heterogeneity.</strong> Am. J. Med. Genet. 164A: 2310-2316, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24939608/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24939608</a>] [<a href="https://doi.org/10.1002/ajmg.a.36646" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24939608">Gos et al. (2014)</a> identified a de novo heterozygous c.270G-C transversion (c.270G-C, NM_006912) in the RIT1 gene, resulting in a met90-to-ile (M90I) substitution at a highly conserved residue in the GTPase domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the dbSNP, 1000 Genomes Project, or Exome Variant Server databases. Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24939608" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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<a id="Aoki2013" class="mim-anchor"></a>
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Aoki, Y., Niihori, T., Banjo, T., Okamoto, N., Mizuno, S., Kurosawa, K., Ogata, T., Takada, F., Yano, M., Ando, T., Hoshika, T., Barnett, C., and 13 others.
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<strong>Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK pathway syndrome.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23791108/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23791108</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23791108[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=23791108" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ajhg.2013.05.021" target="_blank">Full Text</a>]
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<a id="Bertola2014" class="mim-anchor"></a>
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Bertola, D. R., Yamamoto, G. L., Almeida, T. F., Buscarilli, M., Jorge, A. A. L., Malaquias, A. C., Kim, C. A., Takahashi, V. N. V., Passos-Bueno, M. R., Pereira, A. C.
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<strong>Further evidence of the importance of RIT1 in Noonan syndrome.</strong>
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Am. J. Med. Genet. 164A: 2952-2957, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25124994/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25124994</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25124994" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.36722" target="_blank">Full Text</a>]
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<a id="Castel2019" class="mim-anchor"></a>
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Castel, P., Cheng, A., Cuevas-Navarro, A., Everman, D. B., Papageorge, A. G., Simanshu, D. K., Tankka, A., Galeas, J., Urisman, A., McCormick, F.
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<strong>RIT1 oncoproteins escape LZTR1-mediated proteolysis.</strong>
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Science 363: 1226-1230, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30872527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30872527</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30872527[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=30872527" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.aav1444" target="_blank">Full Text</a>]
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<a id="Gos2014" class="mim-anchor"></a>
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Gos, M., Fahiminiya, S., Poznanski, J., Klapecki, J., Obersztyn, E., Piotrowicz, M., Wierzba, J., Posmyk, R., Bal, J., Majewski, J.
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<strong>Contribution of RIT1 mutations to the pathogenesis of Noonan syndrome: four new cases and further evidence of heterogeneity.</strong>
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Am. J. Med. Genet. 164A: 2310-2316, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24939608/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24939608</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24939608" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.36646" target="_blank">Full Text</a>]
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<a id="Heo2006" class="mim-anchor"></a>
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Heo, W. D., Inoue, T., Park, W. S., Kim, M. L., Park, B. O., Wandless, T. J., Meyer, T.
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<strong>PI(3,4,5)P(3) and PI(4,5)P(2) lipids target proteins with polybasic clusters to the plasma membrane.</strong>
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Science 314: 1458-1461, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17095657/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17095657</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17095657[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=17095657" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.1134389" target="_blank">Full Text</a>]
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Hynds, D. L., Spencer, M. L., Andres, D. A., Snow, D. M.
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<strong>Rit promotes MEK-independent neurite branching in human neuroblastoma cells.</strong>
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J. Cell Sci. 116: 1925-1935, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12668729/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12668729</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12668729" 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/10.1242/jcs.00401" target="_blank">Full Text</a>]
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<a id="7" class="mim-anchor"></a>
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<a id="Kouz2016" class="mim-anchor"></a>
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Kouz, K., Lissewski, C., Spranger, S., Mitter, D., Riess, A., Lopez-Gonzalez, V., Luttgen, S., Aydin, H., von Deimling, F., Evers, C., Hahn, A., Hempel, M., and 14 others.
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<strong>Genotype and phenotype in patients with Noonan syndrome and a RIT1 mutation.</strong>
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Genet. Med. 18: 1226-1234, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27101134/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27101134</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27101134" 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/gim.2016.32" target="_blank">Full Text</a>]
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<a id="8" class="mim-anchor"></a>
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<a id="Lee1996" class="mim-anchor"></a>
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Lee, C.-H. J., Della, N. G., Chew, C. E., Zack, D. J.
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<strong>Rin, a neuron-specific and calmodulin-binding small G-protein, and Rit define a novel subfamily of Ras proteins.</strong>
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J. Neurosci. 16: 6784-6794, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8824319/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8824319</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=8824319[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=8824319" 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/10.1523/JNEUROSCI.16-21-06784.1996" target="_blank">Full Text</a>]
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<a id="Shao1999" class="mim-anchor"></a>
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Shao, H., Kadono-Okuda, K., Finlin, B. S., Andres, D. A.
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<strong>Biochemical characterization of the Ras-related GTPases Rit and Rin.</strong>
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Arch. Biochem. Biophys. 371: 207-219, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10545207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10545207</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10545207" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1006/abbi.1999.1448" target="_blank">Full Text</a>]
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<a id="Shi2005" class="mim-anchor"></a>
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Shi, G.-X., Andres, D. A.
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<strong>Rit contributes to nerve growth factor-induced neuronal differentiation via activation of B-Raf-extracellular signal-regulated kinase and p38 mitogen-activated protein kinase cascades.</strong>
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Molec. Cell. Biol. 25: 830-846, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15632082/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15632082</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15632082[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=15632082" 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/10.1128/MCB.25.2.830-846.2005" target="_blank">Full Text</a>]
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Wes, P. D., Yu, M., Montell, C.
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<strong>RIC, a calmodulin-binding Ras-like GTPase.</strong>
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EMBO J. 15: 5839-5848, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8918462/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8918462</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8918462" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Ada Hamosh - updated : 08/28/2019
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Ada Hamosh - updated : 03/03/2017<br>Cassandra L. Kniffin - updated : 5/12/2015<br>Ingrid M. Wentzensen - updated : 12/12/2014<br>Cassandra L. Kniffin - updated : 8/1/2013<br>Ada Hamosh - updated : 2/6/2007
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Patricia A. Hartz : 9/20/2005
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alopez : 03/16/2022
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alopez : 08/28/2019<br>alopez : 03/03/2017<br>alopez : 10/05/2016<br>carol : 05/14/2015<br>mcolton : 5/13/2015<br>ckniffin : 5/12/2015<br>carol : 12/15/2014<br>mcolton : 12/12/2014<br>carol : 8/2/2013<br>ckniffin : 8/1/2013<br>alopez : 2/8/2007<br>alopez : 2/8/2007<br>terry : 2/6/2007<br>carol : 9/29/2005<br>mgross : 9/20/2005
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RAS-LIKE PROTEIN EXPRESSED IN MANY TISSUES; RIT<br />
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ROC1
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</span>
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</h4>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: RIT1</em></strong>
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</span>
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</p>
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</div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 1q22
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Genomic coordinates <span class="small">(GRCh38)</span> : 1:155,897,808-155,911,349 </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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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
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1q22
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</span>
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</td>
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<td>
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<span class="mim-font">
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Noonan syndrome 8
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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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615355
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>RIT belongs to the RAS (HRAS; 190020) subfamily of small GTPases (Hynds et al., 2003). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By PCR using degenerate primers based on the conserved G3 and G4 domains of RAS, followed by screening a mouse retina cDNA library, Lee et al. (1996) cloned mouse Rit. The deduced 219-amino acid protein has a calculated molecular mass of 25.6 kD. By EST database analysis, Lee et al. (1996) identified human RIT. The deduced human protein contains 219 amino acids and shares 94% identity with mouse Rit. Human and mouse RIT have 5 highly conserved domains characteristic of small G proteins, but they lack the C-terminal CAAX prenylation motif found in several other RAS-like proteins. Northern blot analysis detected a 1.2-kb transcript in all mouse tissues examined. Epitope-tagged mouse Rit localized to the plasma membrane of transfected cells. </p><p>By searching an EST database for sequences similar to Drosophila Ric, Wes et al. (1996) identified human RIT and RIN (609592). The core GTPase domain of RIT shares 76% identity with that of RIN, and there is only 1 conservative substitution between the 2 human proteins and Drosophila Ric within the effector G2 region. Northern blot analysis detected RIT transcripts of 1.35, 2.9, and 3.9 kb in most tissues examined. </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>Lee et al. (1996) demonstrated that mouse Rit bound radiolabeled GTP. </p><p>Shao et al. (1999) demonstrated that recombinant human RIT and RIN bound GTP and exhibited intrinsic GTPase activity. Conversion of gln79 to leu in RIT resulted in complete loss of GTPase activity. The activity of RIT and RIN was significantly different from that of the majority of RAS-related GTPases, and the GTP dissociation rates were 5- to 10-fold faster than most RAS-like GTPases. Yeast 2-hybrid analysis showed that RIT and RIN interacted with the RAS-binding proteins RALGDS (601619), RLF (180610), and AF6 (MLLT4; 159559), but not with RAF kinases (e.g., RAF1; 164760), RIN1 (605965), or the p110 subunit of PI3K (see 171834). Shao et al. (1999) concluded that RIT and RIN regulate signaling pathways and cellular processes distinct from those controlled by RAS. </p><p>By expression of RIT in a human neuroblastoma cell line, Hynds et al. (2003) demonstrated that RIT increased neurite outgrowth and branching through MEK (see MEK1; 176872)-dependent and MEK-independent signaling mechanisms, respectively. Adenoviral expression of wildtype or constitutively active RIT increased neurite initiation, elongation, and branching on endogenous matrix or a purified laminin-1 substratum. This outgrowth was morphologically distinct from that promoted by constitutively active RAS or RAF. Constitutively active RIT increased phosphorylation of ERK1 (MAPK3; 601795)/ERK2 (MAPK1; 176948), but not AKT (see AKT1; 164730). A MEK inhibitor blocked RIT-induced neurite initiation, but not elongation or branching. </p><p>Shi and Andres (2005) found that stimulation of a rat pheochromocytoma cell line by growth factors, including nerve growth factor (NGF; 162030), resulted in rapid and prolonged Rit activation. Ectopic expression of active human RIT promoted neurite outgrowth and stimulated activation of both Erk and p38 MAP kinase (MAPK14; 600289) signaling pathways. RIT-induced differentiation depended upon both MAP kinase cascades, since MEK inhibition blocked RIT-induced neurite outgrowth, and p38 blockade inhibited neurite elongation and branching, but not neurite initiation. Moreover, the ability of NGF to promote neuronal differentiation was attenuated by Rit knockdown. </p><p>Heo et al. (2006) surveyed plasma membrane targeting mechanisms by imaging the subcellular localization of 125 fluorescent protein-conjugated Ras, Rab, Arf, and Rho proteins. Of 48 proteins that were localized to the plasma membrane, 37 contained clusters of positively charged amino acids. To test whether these polybasic clusters bind negatively charged phosphatidylinositol 4,5-bisphosphate lipids, Heo et al. (2006) developed a chemical phosphatase activation method to deplete plasma membrane phosphatidylinositol 4,5-bisphosphate. Unexpectedly, proteins with polybasic clusters dissociated from the plasma membrane only when both phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate were depleted, arguing that both lipid second messengers jointly regulate plasma membrane targeting. </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>Wes et al. (1996) stated that the RIT gene was mapped to chromosome 1 by somatic cell hybrid analysis. The mouse Rit gene maps to chromosome 3. </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>Molecular Genetics</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>In 17 unrelated patients with Noonan syndrome-8 (NS8; 615355), Aoki et al. (2013) identified heterozygous mutations in the RIT1 gene (see, e.g., 609591.0001-609591.0004). The first mutations were found by exome sequencing and subsequent mutations were identified from a larger cohort of patients screened for the RIT1 gene. A total of 9 missense mutations were found in 17 (9%) of 180 individuals suspected to have the disorder. The phenotype was characterized by short stature, distinctive facial features, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. A subset of patients showed intellectual disabilities. All of the mutations occurred de novo, except in 1 patient who inherited the mutation from a mother with a Noonan syndrome phenotype. The mutations tended to cluster in the switch II region, and in vitro functional expression studies of 3 of the mutations showed that they resulted in a gain of function. Transfection of 2 of the mutations into zebrafish embryos resulted in a variety of developmental defects, including gastrulation defects, craniofacial abnormalities, pericardial edema, and elongated yolk sac. A smaller percentage of mutant embryos showed even more disorganized growth and abnormal cardiogenesis. The findings were similar to those observed with mutations in other RAS genes (see, e.g., PTPN11, 176876; SOS1, 182530; NRAS, 164790) causing other forms of Noonan syndrome. </p><p>In 6 Brazilian patients with Noonan syndrome but without mutation in selected exons of any known Noonan syndrome-causing genes, Bertola et al. (2014) identified 4 heterozygous missense mutations in the RIT1 gene, all of which had previously been identified in patients with NS8 by Aoki et al. (2013). The mutations were identified by exome sequencing. Parental DNA, which was available for only 2 patients, showed that the mutations were probably de novo. The affected patients had a high frequency of high birthweight, relative macrocephaly, left ventricular hypertrophy, and ectodermal findings such as curly hair, hyperpigmentation, and wrinkled palms and soles. There was no apparent intellectual disability, but formal testing was not performed. Other findings were similar to those observed with mutations in genes causing different forms of Noonan syndrome. Bertola et al. (2014) suggested possible hotspots at residues 57 and 95 of the protein due to recurrent mutations, and recommended that RIT1 be added to gene panels for the molecular diagnosis of Noonan syndrome. </p><p>In 4 unrelated Polish girls with NS8, Gos et al. (2014) identified 3 different heterozygous missense mutations in the RIT1 gene (609591.0004-609591.0006). The mutations in the first 2 patients were found by whole-exome sequencing after mutations in common Noonan syndrome genes were excluded. The mutations in the second 2 patients were found by direct sequencing of the RIT1 gene in 64 patients with Noonan syndrome. Functional studies of the variants were not performed. The RIT1 mutation rate in this study was estimated at 3.8% (4 of 106 NS patients). </p><p>Kouz et al. (2016) sequenced RIT1 in 310 mutation-negative individuals with a suspected RASopathy and prospectively in individuals who underwent genetic testing for NS. Eleven different RIT1 missense mutations, 3 of which were novel, were identified in 33 subjects from 28 families; codons 57, 82, and 95 represent mutation hotspots. RIT1 is 1 of the 4 most common genes mutated in Noonan syndrome. </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>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>Castel et al. (2019) used an isogenic germline knockin mouse model to study the effects of RIT1 mutation at the organismal level, which resulted in a phenotype resembling Noonan syndrome. By mass spectrometry, Castel et al. (2019) detected a RIT1 interactor, LZTR1 (600574), that acts as an adaptor for protein degradation. Pathogenic mutations affecting either RIT1 or LZTR1 resulted in incomplete degradation of RIT1. This led to RIT1 accumulation and dysregulated growth factor signaling responses. Castel et al. (2019) concluded that their results highlighted a mechanism of pathogenesis that relies on impaired protein degradation of the Ras GTPase RIT1. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>6 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 NOONAN SYNDROME 8</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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RIT1, ALA57GLY
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<br />
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SNP: rs672601334,
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ClinVar: RCV000054404, RCV000159100, RCV000207349, RCV000856747, RCV001731346, RCV001813373, RCV002399414, RCV003390753
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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 4 unrelated patients with Noonan syndrome-8 (NS8; 615355), Aoki et al. (2013) identified a de novo heterozygous c.170C-G transversion in exon 4 of the RIT1 gene, resulting in an ala57-to-gly (A57G) substitution at a conserved residue. In vitro cellular expression studies showed that the A57G mutation resulted in a gain of function. </p><p>In 2 unrelated Brazilian patients with NS8, Bertola et al. (2014) identified heterozygosity for the A57G mutation. </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 NOONAN SYNDROME 8</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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RIT1, GLU81GLY
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<br />
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SNP: rs869025193,
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ClinVar: RCV000054405, RCV000207350, RCV000255048, RCV000508083, RCV001174556, RCV001265779, RCV001813418, RCV004745234
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with Noonan syndrome-8 (NS8; 615355), Aoki et al. (2013) identified a de novo heterozygous c.242A-G transition in exon 5 of the RIT1 gene, resulting in a glu81-to-gly (E81G) substitution at a conserved residue. In vitro cellular expression studies showed that the E81G mutation resulted in a gain of function. Transfection of the E81G mutation into zebrafish embryos resulted in a variety of developmental defects, including gastrulation defects, craniofacial abnormalities, pericardial edema, and elongated yolk sac. A smaller percentage of mutant embryos showed even more disorganized growth and abnormal cardiogenesis. </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 NOONAN SYNDROME 8</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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RIT1, PHE82LEU
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<br />
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SNP: rs730881014,
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gnomAD: rs730881014,
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ClinVar: RCV000054406, RCV000159101, RCV000207343, RCV001255602, RCV001375970, RCV001813414, RCV003398818, RCV003483526
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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 patients with Noonan syndrome-8 (NS8; 615355), Aoki et al. (2013) identified a de novo heterozygous c.246T-G transversion in exon 5 of the RIT1 gene, resulting in a phe82-to-leu (F82L) substitution at a conserved residue. The mutation, which was initially found by exome sequencing, was not present in several control databases. In vitro cellular expression studies showed that the F82L mutation resulted in 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>.0004 NOONAN SYNDROME 8</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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RIT1, GLY95ALA
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<br />
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SNP: rs672601335,
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ClinVar: RCV000054407, RCV000207348, RCV000298790, RCV001192384, RCV001813374, RCV002433549, RCV003450918, RCV003915017
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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 4 unrelated patients with Noonan syndrome-8 (NS8; 615355), Aoki et al. (2013) identified a de novo heterozygous c.284G-C transversion in exon 5 of the RIT1 gene, resulting in a gly95-to-ala (G95A) substitution. The mutation, which was initially found by exome sequencing, was not present in several control databases. In vitro cellular expression studies showed that the G95A mutation resulted in a gain of function. Transfection of the G95A mutation into zebrafish embryos resulted in a variety of developmental defects, including gastrulation defects, craniofacial abnormalities, pericardial edema, and elongated yolk sac. A smaller percentage of mutant embryos showed even more disorganized growth and abnormal cardiogenesis. </p><p>In 2 unrelated Brazilian patients with NS8, Bertola et al. (2014) identified heterozygosity for the G95A mutation. </p><p>Gos et al. (2014) identified a heterozygous G95A mutation in 2 unrelated Polish girls with NS8. </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 8</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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RIT1, PHE82VAL
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<br />
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SNP: rs869025194,
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ClinVar: RCV000170492, RCV000207352, RCV000263369, RCV001778757, RCV001813420, RCV002453562
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a 6-year-old Polish girl with Noonan syndrome-8 (NS8; 615355), Gos et al. (2014) identified a de novo heterozygous c.244T-G transversion (c.244T-G, NM_006912) in the RIT1 gene, resulting in a phe82-to-val (F82V) substitution at a highly conserved residue in the GTPase domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the dbSNP, 1000 Genomes Project, or Exome Variant Server databases. Functional studies of the variant were not performed. A different mutation at the same codon has been reported (F82L; 609591.0003). </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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<strong>.0006 NOONAN SYNDROME 8</strong>
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RIT1, MET90ILE
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<br />
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SNP: rs483352822,
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ClinVar: RCV000170493, RCV000355969, RCV001813422, RCV003416059, RCV004020021
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<p>In a 5.5-year-old Polish girl with Noonan syndrome-8 (NS8; 615355), Gos et al. (2014) identified a de novo heterozygous c.270G-C transversion (c.270G-C, NM_006912) in the RIT1 gene, resulting in a met90-to-ile (M90I) substitution at a highly conserved residue in the GTPase domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the dbSNP, 1000 Genomes Project, or Exome Variant Server databases. Functional studies of the variant were not performed. </p>
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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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<p />
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Aoki, Y., Niihori, T., Banjo, T., Okamoto, N., Mizuno, S., Kurosawa, K., Ogata, T., Takada, F., Yano, M., Ando, T., Hoshika, T., Barnett, C., and 13 others.
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<strong>Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK pathway syndrome.</strong>
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Am. J. Hum. Genet. 93: 173-180, 2013.
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[PubMed: 23791108]
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[Full Text: https://doi.org/10.1016/j.ajhg.2013.05.021]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Bertola, D. R., Yamamoto, G. L., Almeida, T. F., Buscarilli, M., Jorge, A. A. L., Malaquias, A. C., Kim, C. A., Takahashi, V. N. V., Passos-Bueno, M. R., Pereira, A. C.
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<strong>Further evidence of the importance of RIT1 in Noonan syndrome.</strong>
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Am. J. Med. Genet. 164A: 2952-2957, 2014.
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[PubMed: 25124994]
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[Full Text: https://doi.org/10.1002/ajmg.a.36722]
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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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Castel, P., Cheng, A., Cuevas-Navarro, A., Everman, D. B., Papageorge, A. G., Simanshu, D. K., Tankka, A., Galeas, J., Urisman, A., McCormick, F.
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<strong>RIT1 oncoproteins escape LZTR1-mediated proteolysis.</strong>
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Science 363: 1226-1230, 2019.
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[PubMed: 30872527]
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[Full Text: https://doi.org/10.1126/science.aav1444]
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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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Gos, M., Fahiminiya, S., Poznanski, J., Klapecki, J., Obersztyn, E., Piotrowicz, M., Wierzba, J., Posmyk, R., Bal, J., Majewski, J.
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<strong>Contribution of RIT1 mutations to the pathogenesis of Noonan syndrome: four new cases and further evidence of heterogeneity.</strong>
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Am. J. Med. Genet. 164A: 2310-2316, 2014.
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[PubMed: 24939608]
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[Full Text: https://doi.org/10.1002/ajmg.a.36646]
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</li>
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<li>
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<p class="mim-text-font">
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Heo, W. D., Inoue, T., Park, W. S., Kim, M. L., Park, B. O., Wandless, T. J., Meyer, T.
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<strong>PI(3,4,5)P(3) and PI(4,5)P(2) lipids target proteins with polybasic clusters to the plasma membrane.</strong>
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Science 314: 1458-1461, 2006.
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[PubMed: 17095657]
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[Full Text: https://doi.org/10.1126/science.1134389]
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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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Hynds, D. L., Spencer, M. L., Andres, D. A., Snow, D. M.
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<strong>Rit promotes MEK-independent neurite branching in human neuroblastoma cells.</strong>
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J. Cell Sci. 116: 1925-1935, 2003.
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[PubMed: 12668729]
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[Full Text: https://doi.org/10.1242/jcs.00401]
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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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Kouz, K., Lissewski, C., Spranger, S., Mitter, D., Riess, A., Lopez-Gonzalez, V., Luttgen, S., Aydin, H., von Deimling, F., Evers, C., Hahn, A., Hempel, M., and 14 others.
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<strong>Genotype and phenotype in patients with Noonan syndrome and a RIT1 mutation.</strong>
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Genet. Med. 18: 1226-1234, 2016.
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[PubMed: 27101134]
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[Full Text: https://doi.org/10.1038/gim.2016.32]
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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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Lee, C.-H. J., Della, N. G., Chew, C. E., Zack, D. J.
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<strong>Rin, a neuron-specific and calmodulin-binding small G-protein, and Rit define a novel subfamily of Ras proteins.</strong>
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J. Neurosci. 16: 6784-6794, 1996.
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[PubMed: 8824319]
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[Full Text: https://doi.org/10.1523/JNEUROSCI.16-21-06784.1996]
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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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Shao, H., Kadono-Okuda, K., Finlin, B. S., Andres, D. A.
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<strong>Biochemical characterization of the Ras-related GTPases Rit and Rin.</strong>
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Arch. Biochem. Biophys. 371: 207-219, 1999.
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[PubMed: 10545207]
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[Full Text: https://doi.org/10.1006/abbi.1999.1448]
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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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Shi, G.-X., Andres, D. A.
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<strong>Rit contributes to nerve growth factor-induced neuronal differentiation via activation of B-Raf-extracellular signal-regulated kinase and p38 mitogen-activated protein kinase cascades.</strong>
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Molec. Cell. Biol. 25: 830-846, 2005.
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[PubMed: 15632082]
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[Full Text: https://doi.org/10.1128/MCB.25.2.830-846.2005]
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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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Wes, P. D., Yu, M., Montell, C.
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<strong>RIC, a calmodulin-binding Ras-like GTPase.</strong>
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EMBO J. 15: 5839-5848, 1996.
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[PubMed: 8918462]
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</p>
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</li>
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</ol>
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<span class="mim-text-font">
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Ada Hamosh - updated : 08/28/2019<br>Ada Hamosh - updated : 03/03/2017<br>Cassandra L. Kniffin - updated : 5/12/2015<br>Ingrid M. Wentzensen - updated : 12/12/2014<br>Cassandra L. Kniffin - updated : 8/1/2013<br>Ada Hamosh - updated : 2/6/2007
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Patricia A. Hartz : 9/20/2005
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alopez : 03/16/2022<br>alopez : 08/28/2019<br>alopez : 03/03/2017<br>alopez : 10/05/2016<br>carol : 05/14/2015<br>mcolton : 5/13/2015<br>ckniffin : 5/12/2015<br>carol : 12/15/2014<br>mcolton : 12/12/2014<br>carol : 8/2/2013<br>ckniffin : 8/1/2013<br>alopez : 2/8/2007<br>alopez : 2/8/2007<br>terry : 2/6/2007<br>carol : 9/29/2005<br>mgross : 9/20/2005
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