3348 lines
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Entry
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- *300142 - p21 PROTEIN-ACTIVATED KINASE 3; PAK3
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- OMIM
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<p>
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<span class="h4">*300142</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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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<li role="presentation">
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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="#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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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/300142">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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</li>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000077264;t=ENST00000372007" 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=5063" 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=300142" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000077264;t=ENST00000372007" 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_001128166,NM_001128167,NM_001128168,NM_001128172,NM_001128173,NM_001324325,NM_001324326,NM_001324327,NM_001324328,NM_001324329,NM_001324330,NM_001324331,NM_001324332,NM_001324333,NM_001324334,NM_002578,NR_136740,NR_136741,NR_136742,NR_136743,NR_136744,NR_136745,NR_136746,NR_136747,NR_136748,XM_005262132,XM_005262133,XM_006724654,XM_006724655,XM_011530962,XM_011530968,XM_011530969,XM_011530971,XM_017029557,XM_017029558,XM_017029559,XM_017029560,XM_017029563,XM_047442146,XM_047442147,XM_047442148,XM_047442149,XM_047442150" 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_002578" 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=300142" 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=02142&isoform_id=02142_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/PAK3" 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/3608386,4505601,7677056,33353243,33353245,33353247,33353249,33353251,33353253,33353255,33353257,33353259,33353261,33353263,33353265,33353267,33353269,33353271,33353273,33353275,33353277,33353279,33353281,33353303,33353305,33353307,33353309,33353311,33353313,33353315,33353317,33353319,33353321,33353323,33353325,33353327,33353329,33353331,33353333,33353335,33353337,33353339,33353341,33353363,33353365,33353367,33353369,33353371,33353373,33353375,33353377,33353379,33353381,33353383,33353385,33353387,33353389,33353391,33353393,33353395,33353397,33353399,33353401,33354089,47117818,119623058,119623059,158254440,169643240,169643242,169643244,189054852,189491751,189491753,189491755,189491757,189491759,530422051,530422053,578838378,578838380,768037787,768037808,768037812,768037829,1024249254,1024249265,1024249269,1024249292,1024249297,1024249303,1024249319,1024249336,1024249340,1024249348,1034674434,1034674436,1034674438,1034674440,1034674447,2217392526,2217392531,2217392533,2217392535,2217392537,2462629630,2462629632,2462629634,2462629636,2462629638,2462629640,2462629642,2462629644,2462629646,2462629648,2462629650,2462629652,2462629654,2462629657,2462629659,2462629661,2462629664" 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/O75914" 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=5063" 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=ENSG00000077264;t=ENST00000372007" 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=PAK3" 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=PAK3" 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+5063" 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/PAK3" 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:5063" 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/5063" 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=chrX&hgg_gene=ENST00000372007.10&hgg_start=110944397&hgg_end=111227361&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">
|
|
<span class="panel-title">
|
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<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:8592" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:8592" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=300142[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=300142[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/PAK3/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/ENSG00000077264" 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=PAK3" 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=PAK3" 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=PAK3" 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=PAK3&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/PA32919" 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:8592" 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/FBgn0044826.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:1339656" 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/PAK3#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:1339656" 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/5063/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=5063" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00003911;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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</div>
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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">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
|
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<span class="small">
|
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
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<div style="display: table-cell;">Cellular Pathways</div>
|
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</div>
|
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</a>
|
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:5063" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=PAK3&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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300142
|
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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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|
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p21 PROTEIN-ACTIVATED KINASE 3; PAK3
|
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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>
|
|
<a id="alternativeTitles" class="mim-anchor"></a>
|
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<div>
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<p>
|
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<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
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</p>
|
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</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
p21 CDC42/RAC1-ACTIVATED KINASE 3<br />
|
|
OLIGOPHRENIN 3; OPHN3
|
|
</span>
|
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</h4>
|
|
</div>
|
|
</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>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=PAK3" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">PAK3</a></em></strong>
|
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</span>
|
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</p>
|
|
</div>
|
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/X/573?start=-3&limit=10&highlight=573">Xq23</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chrX:110944397-111227361&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'})">X:110,944,397-111,227,361</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
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|
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|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
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|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
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<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/X/573?start=-3&limit=10&highlight=573">
|
|
Xq23
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Intellectual developmental disorder, X-linked 30
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/300558"> 300558 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="X-linked recessive">XLR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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|
|
</span>
|
|
</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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<p>Ras (HRAS; <a href="/entry/190020">190020</a>)-related GTPases, or p21 proteins, of the Rho (RHOA; <a href="/entry/165390">165390</a>) subfamily are critical regulators of signal transduction pathways. The p21-activated kinases (PAKs) are a family of serine/threonine kinases that are central to signal transduction and cellular regulation. PAKs are involved in a variety of cellular processes, including cytoskeletal dynamics, cell motility, gene transcription, death and survival signaling, and cell cycle progression. Consequently, PAKs are implicated in numerous pathologic conditions and in cell transformation. The PAK family is divided into 2 subfamilies, group I and group II, based on domain architecture and regulation. Group I, the conventional PAKs, includes PAK1 (<a href="/entry/602590">602590</a>), PAK2 (<a href="/entry/605022">605022</a>), and PAK3, which are activated upon binding the GTP-bound forms of the Rho GTPases CDC42 (<a href="/entry/116952">116952</a>) and RAC1 (<a href="/entry/602048">602048</a>). Group II, the nonconventional PAKs, includes PAK4 (<a href="/entry/605451">605451</a>), PAK5 (PAK7; <a href="/entry/608038">608038</a>), and PAK6 (<a href="/entry/608110">608110</a>), which are active independent of Rho GTPases (reviews by <a href="#16" class="mim-tip-reference" title="Zhao, Z., Manser, E. <strong>PAK and other Rho-associated kinases--effectors with surprisingly diverse mechanisms of regulation.</strong> Biochem. J. 386: 201-214, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15548136/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15548136</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15548136[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/10.1042/BJ20041638" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15548136">Zhao and Manser (2005)</a> and <a href="#7" class="mim-tip-reference" title="Eswaran, J., Soundararajan, M., Kumar, R., Knapp, S. <strong>UnPAKing the class differences among p21-activated kinases.</strong> Trends Biochem. Sci. 33: 394-403, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18639460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18639460</a>] [<a href="https://doi.org/10.1016/j.tibs.2008.06.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18639460">Eswaran et al. (2008)</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15548136+18639460" 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 screening rat brain cytosol for proteins that interacted with Ras (HRAS; <a href="/entry/190020">190020</a>)-related GTPases, or p21 proteins, of the Rho (RHOA; <a href="/entry/165390">165390</a>) subfamily, <a href="#13" class="mim-tip-reference" title="Manser, E., Leung, T., Salihuddin, H., Zhao, Z., Lim, L. <strong>A brain serine/threonine protein kinase activated by Cdc42 and Rac1.</strong> Nature 367: 40-46, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8107774/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8107774</a>] [<a href="https://doi.org/10.1038/367040a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8107774">Manser et al. (1994)</a> identified 3 proteins that interacted with the GTP-bound forms of human CDC42 (<a href="/entry/116952">116952</a>) and RAC1 (<a href="/entry/602048">602048</a>), but not RHOA. <a href="#12" class="mim-tip-reference" title="Manser, E., Chong, C., Zhao, Z. S., Leung, T., Michael, G., Hall, C., Lim, L. <strong>Molecular cloning of a new member of the p21-Cdc42/Rac-activated kinase (PAK) family.</strong> J. Biol. Chem. 270: 25070-25078, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7559638/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7559638</a>] [<a href="https://doi.org/10.1074/jbc.270.42.25070" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7559638">Manser et al. (1995)</a> isolated a rat cDNA encoding 1 of these proteins, Pak3. <a href="#2" class="mim-tip-reference" title="Bagrodia, S., Taylor, S. J., Creasy, C. L., Chernoff, J., Cerione, R. A. <strong>Identification of a mouse p21Cdc/Rac activated kinase.</strong> J. Biol. Chem. 270: 22731-22737, 1995. Note: Erratum: J. Biol. Chem. 271: 1250 only, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7559398/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7559398</a>] [<a href="https://doi.org/10.1074/jbc.270.39.22731" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7559398">Bagrodia et al. (1995)</a> cloned mouse Pak3. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7559638+7559398+8107774" 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="Chelly, J. <strong>Breakthroughs in molecular and cellular mechanisms underlying X-linked mental retardation.</strong> Hum. Molec. Genet. 8: 1833-1838, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10469834/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10469834</a>] [<a href="https://doi.org/10.1093/hmg/8.10.1833" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10469834">Chelly (1999)</a> referred to the PAK3 gene as oligophrenin-3 (OPHN3). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10469834" 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 Northern blot analysis of adult mouse tissues, <a href="#11" class="mim-tip-reference" title="Kohn, M., Steinbach, P., Hameister, H., Kehrer-Sawatzki, H. <strong>A comparative expression analysis of four MRX genes regulating intracellular signalling via small GTPases.</strong> Europ. J. Hum. Genet. 12: 29-37, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14673471/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14673471</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201085" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14673471">Kohn et al. (2004)</a> observed 3 isoforms of Pak3: a 2.2-kb testis-specific transcript, a 2.4-kb transcript expressed in brain and testis, and an approximately 3-kb transcript expressed in kidney and brain. In situ hybridization on mouse embryo sections showed that Pak3 was not expressed at early midgestational stages, showed its highest expression at the base of the diencephalon in the supraoptic area at embryonic day 11.5, and showed more expression in the subventricular zone at embryonic day 14.5. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14673471" 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="#9" class="mim-tip-reference" title="Gross, M. B. <strong>Personal Communication.</strong> Baltimore, Md. 5/9/2011."None>Gross (2011)</a> mapped the PAK3 gene to chromosome Xq23 based on an alignment of the PAK3 sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=AF155651" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">AF155651</a>) with the genomic sequence (GRCh37).</p>
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<p>In affected members of an Australian family with a form of nonsyndromic X-linked intellectual developmental disorder (XLID30; <a href="/entry/300558">300558</a>) found by <a href="#6" class="mim-tip-reference" title="Donnelly, A. J., Partington, M. W., Ryan, A. K., Mulley, J. C. <strong>Regional localisation of two non-specific X-linked mental retardation genes (MRX30 and MRX31).</strong> Am. J. Med. Genet. 64: 113-120, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8826460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8826460</a>] [<a href="https://doi.org/10.1002/(SICI)1096-8628(19960712)64:1<113::AID-AJMG19>3.0.CO;2-Q" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8826460">Donnelly et al. (1996)</a> to map to chromosome Xq21.3-q24, <a href="#1" class="mim-tip-reference" title="Allen, K. M., Gleeson, J. G., Bagrodia, S., Partington, M. W., MacMillan, J. C., Cerione, R. A., Mulley, J. C., Walsh, C. A. <strong>PAK3 mutation in nonsyndromic X-linked mental retardation.</strong> Nature Genet. 20: 25-30, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9731525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9731525</a>] [<a href="https://doi.org/10.1038/1675" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9731525">Allen et al. (1998)</a> identified a mutation in the PAK3 gene (<a href="#0001">300142.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8826460+9731525" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of a French family with XLID reported by <a href="#5" class="mim-tip-reference" title="des Portes, V., Soufir, N., Carrie, A., Billuart, P., Bienvenu, T., Vinet, M. C., Beldjord, C., Ponsot, G., Kahn, A., Boue, J., Chelly, J. <strong>Gene for nonspecific X-linked mental retardation (MRX 47) is located in Xq22.3-q24.</strong> Am. J. Med. Genet. 72: 324-328, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9332663/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9332663</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(19971031)72:3<324::aid-ajmg14>3.0.co;2-v" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9332663">des Portes et al. (1997)</a>, <a href="#3" class="mim-tip-reference" title="Bienvenu, T., des Portes, V., McDonell, N., Carrie, A., Zemni, R., Couvert, P., Ropers, H. H., Moraine, C., van Bokhoven, H., Fryns, J. P., Allen, K., Walsh, C. A., Boue, J., Kahn, A., Chelly, J., Beldjord, C. <strong>Missense mutation in PAK3, R67C, causes X-linked nonspecific mental retardation.</strong> Am. J. Med. Genet. 93: 294-298, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10946356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10946356</a>] [<a href="https://doi.org/10.1002/1096-8628(20000814)93:4<294::aid-ajmg8>3.0.co;2-f" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10946356">Bienvenu et al. (2000)</a> identified a mutation in the PAK3 gene (<a href="#0002">300142.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9332663+10946356" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#10" class="mim-tip-reference" title="Huang, W., Zhou, Z., Asrar, S., Henkelman, M., Xie, W., Jia, Z. <strong>p21-activated kinases 1 and 3 control brain size through coordinating neuronal complexity and synaptic properties.</strong> Molec. Cell. Biol. 31: 388-403, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21115725/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21115725</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21115725[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.00969-10" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21115725">Huang et al. (2011)</a> noted that knockout of either Pak1 or Pak3 in mice results in no overt abnormality. They found that double knockout (DK) of both Pak1 and Pak3 resulted in mice that were born healthy, with normal brain size and structure. However, postnatal brain growth in DK mice was severely impaired due to reduced neuronal cell volume, reduced axonal and dendritic branching, and reduced synaptic density. Behaviorally, DK mice were hyperactive and anxious, and they exhibited a learning deficit compared with wildtype mice. These structural and functional deficits in DK mice were associated with abnormal electrophysiologic activity in hippocampus and enhanced synaptic cofilin (see <a href="/entry/601442">601442</a>) activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21115725" 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">rs121434611 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434611;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=rs121434611" 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=rs121434611" 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=RCV000012324 OR RCV000656321" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012324, RCV000656321" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012324...</a>
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<p>In affected males of an Australian family with nonsyndromic X-linked intellectual developmental disorder-30 (XLID30; <a href="/entry/300558">300558</a>) reported by <a href="#6" class="mim-tip-reference" title="Donnelly, A. J., Partington, M. W., Ryan, A. K., Mulley, J. C. <strong>Regional localisation of two non-specific X-linked mental retardation genes (MRX30 and MRX31).</strong> Am. J. Med. Genet. 64: 113-120, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8826460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8826460</a>] [<a href="https://doi.org/10.1002/(SICI)1096-8628(19960712)64:1<113::AID-AJMG19>3.0.CO;2-Q" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8826460">Donnelly et al. (1996)</a>, <a href="#1" class="mim-tip-reference" title="Allen, K. M., Gleeson, J. G., Bagrodia, S., Partington, M. W., MacMillan, J. C., Cerione, R. A., Mulley, J. C., Walsh, C. A. <strong>PAK3 mutation in nonsyndromic X-linked mental retardation.</strong> Nature Genet. 20: 25-30, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9731525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9731525</a>] [<a href="https://doi.org/10.1038/1675" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9731525">Allen et al. (1998)</a> identified a 1255C-T transition in the PAK3 gene, resulting in an arg419-to-ter (R419X) substitution. The mutation was not identified in any unaffected males or more than 45 control individuals. When the MRX30 mutation was introduced into PAK3 cDNA and transfected into COS cells, the cDNA produced a stable, albeit truncated, protein with no measurable kinase activity. MRI studies of the more severely affected male with MRX30, who was microcephalic (although several other affected males were not), showed normal gross architecture of the cortex and hippocampus and other structures. Although more subtle defects in neuronal development could not be ruled out, MRI analysis suggested that PAK3 is not absolutely required for neuronal proliferation, migration, or cortical gyration. Therefore, the finding that the PAK3 mutation produces mental retardation may reflect a later requirement for PAK3 in axon outgrowth or function of the adult cortex. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8826460+9731525" 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>.0002 INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 30</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121434612 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434612;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=rs121434612" 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=rs121434612" 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=RCV000012325" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012325" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012325</a>
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<p>In affected males of a French family with nonsyndromic X-linked intellectual developmental disorder-30 (XLID30; <a href="/entry/300558">300558</a>) reported by <a href="#5" class="mim-tip-reference" title="des Portes, V., Soufir, N., Carrie, A., Billuart, P., Bienvenu, T., Vinet, M. C., Beldjord, C., Ponsot, G., Kahn, A., Boue, J., Chelly, J. <strong>Gene for nonspecific X-linked mental retardation (MRX 47) is located in Xq22.3-q24.</strong> Am. J. Med. Genet. 72: 324-328, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9332663/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9332663</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(19971031)72:3<324::aid-ajmg14>3.0.co;2-v" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9332663">des Portes et al. (1997)</a>, <a href="#3" class="mim-tip-reference" title="Bienvenu, T., des Portes, V., McDonell, N., Carrie, A., Zemni, R., Couvert, P., Ropers, H. H., Moraine, C., van Bokhoven, H., Fryns, J. P., Allen, K., Walsh, C. A., Boue, J., Kahn, A., Chelly, J., Beldjord, C. <strong>Missense mutation in PAK3, R67C, causes X-linked nonspecific mental retardation.</strong> Am. J. Med. Genet. 93: 294-298, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10946356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10946356</a>] [<a href="https://doi.org/10.1002/1096-8628(20000814)93:4<294::aid-ajmg8>3.0.co;2-f" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10946356">Bienvenu et al. (2000)</a> identified a 199C-T transition in exon 2 of the PAK3 gene, resulting in an arg67-to-cys (R67C) substitution in a polybasic region upstream of the CDC42/Rac interactive binding domain, and was predicted to affect GTPase binding. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9332663+10946356" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 30</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121434613 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434613;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=rs121434613" 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=rs121434613" 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=RCV000012326 OR RCV003162241" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012326, RCV003162241" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012326...</a>
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<p>In affected males of an Australian family with nonsyndromic X-linked intellectual developmental disorder-30 (XLID30; <a href="/entry/300558">300558</a>), <a href="#8" class="mim-tip-reference" title="Gedeon, A. K., Nelson, J., Gecz, J., Mulley, J. C. <strong>X-linked mild non-syndromic mental retardation with neuropsychiatric problems and the missense mutation A365E in PAK3.</strong> Am. J. Med. Genet. 120A: 509-517, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12884430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12884430</a>] [<a href="https://doi.org/10.1002/ajmg.a.20131" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12884430">Gedeon et al. (2003)</a> identified a 1094C-A transversion in exon 10 of the PAK3 gene, resulting in an ala365-to-glu (A365E) substitution. Affected males had borderline to mild mental retardation and most were able to function independently and hold menial jobs. Several patients had psychiatric disorders and some had relatively long ears. All carrier women had normal intelligence. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12884430" 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>.0004 INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 30</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121434614 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434614;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=rs121434614" 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=rs121434614" 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=RCV000012327" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012327" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012327</a>
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<p>In 5 males with intellectual developmental disorder-30 (XLID30; <a href="/entry/300558">300558</a>) in a Finnish family, <a href="#14" class="mim-tip-reference" title="Peippo, M., Koivisto, A. M., Sarkamo, T., Sipponen, M., von Koskull, H., Ylisaukko-oja, T., Rehnstrom, K., Froyen, G., Ignatius, J., Jarvela, I. <strong>PAK3 related mental disability: further characterization of the phenotype.</strong> Am. J. Med. Genet. 143A: 2406-2416, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17853471/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17853471</a>] [<a href="https://doi.org/10.1002/ajmg.a.31956" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17853471">Peippo et al. (2007)</a> identified a 1337G-C transversion in exon 7 of the PAK3 gene, resulting in a trp446-to-ser (W446S) substitution. Each mother of an affected male was found to be a carrier of the mutation. <a href="#14" class="mim-tip-reference" title="Peippo, M., Koivisto, A. M., Sarkamo, T., Sipponen, M., von Koskull, H., Ylisaukko-oja, T., Rehnstrom, K., Froyen, G., Ignatius, J., Jarvela, I. <strong>PAK3 related mental disability: further characterization of the phenotype.</strong> Am. J. Med. Genet. 143A: 2406-2416, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17853471/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17853471</a>] [<a href="https://doi.org/10.1002/ajmg.a.31956" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17853471">Peippo et al. (2007)</a> examined X inactivation in carrier females by the methylation status of the polymorphic AR locus (<a href="/entry/313700">313700</a>). Skewed X inactivation was identified in 2 phenotypically normal females (90%:10%; 91%:9%) as well as in a borderline retarded female (100%:0%). The mutation was not found in 2 male relatives or in 200 unrelated Finnish controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17853471" 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">rs1569398769 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1569398769;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=rs1569398769" 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=rs1569398769" 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=RCV000012328 OR RCV001257660 OR RCV003329230" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012328, RCV001257660, RCV003329230" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012328...</a>
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<p>In 3 affected males from a Tunisian family with X-linked intellectual developmental disorder-30 (XLID30; <a href="/entry/300558">300558</a>), <a href="#15" class="mim-tip-reference" title="Rejeb, I., Saillour, Y., Castelnau, L., Julien, C., Bienvenu, T., Taga, P., Chaabouni, H., Chelly, J., Jemaa, L. B., Bahi-Buisson, N. <strong>A novel splice mutation in PAK3 gene underlying mental retardation with neuropsychiatric features.</strong> Europ. J. Hum. Genet. 16: 1358-1363, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18523455/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18523455</a>] [<a href="https://doi.org/10.1038/ejhg.2008.103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18523455">Rejeb et al. (2008)</a> identified an A-to-G transition (276+4G-A) in intron 6 of the PAK3 gene, predicted to result in a novel donor splice site. RT-PCR analysis of patient RNA showed that the mutation resulted in a 4-bp insertion, frameshift, and premature termination at codon 128. The mutation was not identified in 200 control individuals. The phenotype was homogeneous, with microcephaly, oral motor dysfunction, and behavioral disturbances. X-inactivation studies showed completely skewed X inactivation in 2 female carriers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18523455" 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://doi.org/10.1074/jbc.270.39.22731" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/1096-8628(20000814)93:4<294::aid-ajmg8>3.0.co;2-f" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/8.10.1833" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/(SICI)1096-8628(19960712)64:1<113::AID-AJMG19>3.0.CO;2-Q" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.20131" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1128/MCB.00969-10" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1042/BJ20041638" target="_blank">Full Text</a>]
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Patricia A. Hartz - updated : 12/22/2011
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Matthew B. Gross - updated : 5/9/2011<br>Cassandra L. Kniffin - updated : 8/31/2009<br>Kelly A. Przylepa - updated : 4/1/2008<br>Cassandra L. Kniffin - updated : 10/6/2005<br>Marla J. F. O'Neill - updated : 5/6/2004<br>Victor A. McKusick - updated : 10/12/1999
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 8/28/1998
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 08/20/2021
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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mcolton : 05/21/2014<br>carol : 9/12/2013<br>terry : 6/6/2012<br>mgross : 1/9/2012<br>terry : 12/22/2011<br>mgross : 5/9/2011<br>wwang : 9/16/2009<br>ckniffin : 8/31/2009<br>carol : 4/4/2008<br>terry : 4/1/2008<br>carol : 10/7/2005<br>ckniffin : 10/6/2005<br>carol : 5/6/2004<br>carol : 5/6/2004<br>terry : 5/6/2004<br>alopez : 3/17/2004<br>terry : 4/28/2003<br>alopez : 3/11/2003<br>mgross : 5/31/2000<br>carol : 10/12/1999<br>terry : 6/9/1999<br>mgross : 3/16/1999<br>alopez : 8/28/1998
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</span>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 300142
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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p21 PROTEIN-ACTIVATED KINASE 3; PAK3
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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p21 CDC42/RAC1-ACTIVATED KINASE 3<br />
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OLIGOPHRENIN 3; OPHN3
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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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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: PAK3</em></strong>
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: Xq23
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Genomic coordinates <span class="small">(GRCh38)</span> : X:110,944,397-111,227,361 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
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Xq23
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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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Intellectual developmental disorder, X-linked 30
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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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300558
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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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X-linked recessive
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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>Ras (HRAS; 190020)-related GTPases, or p21 proteins, of the Rho (RHOA; 165390) subfamily are critical regulators of signal transduction pathways. The p21-activated kinases (PAKs) are a family of serine/threonine kinases that are central to signal transduction and cellular regulation. PAKs are involved in a variety of cellular processes, including cytoskeletal dynamics, cell motility, gene transcription, death and survival signaling, and cell cycle progression. Consequently, PAKs are implicated in numerous pathologic conditions and in cell transformation. The PAK family is divided into 2 subfamilies, group I and group II, based on domain architecture and regulation. Group I, the conventional PAKs, includes PAK1 (602590), PAK2 (605022), and PAK3, which are activated upon binding the GTP-bound forms of the Rho GTPases CDC42 (116952) and RAC1 (602048). Group II, the nonconventional PAKs, includes PAK4 (605451), PAK5 (PAK7; 608038), and PAK6 (608110), which are active independent of Rho GTPases (reviews by Zhao and Manser (2005) and Eswaran et al. (2008)). </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 screening rat brain cytosol for proteins that interacted with Ras (HRAS; 190020)-related GTPases, or p21 proteins, of the Rho (RHOA; 165390) subfamily, Manser et al. (1994) identified 3 proteins that interacted with the GTP-bound forms of human CDC42 (116952) and RAC1 (602048), but not RHOA. Manser et al. (1995) isolated a rat cDNA encoding 1 of these proteins, Pak3. Bagrodia et al. (1995) cloned mouse Pak3. </p><p>Chelly (1999) referred to the PAK3 gene as oligophrenin-3 (OPHN3). </p><p>By Northern blot analysis of adult mouse tissues, Kohn et al. (2004) observed 3 isoforms of Pak3: a 2.2-kb testis-specific transcript, a 2.4-kb transcript expressed in brain and testis, and an approximately 3-kb transcript expressed in kidney and brain. In situ hybridization on mouse embryo sections showed that Pak3 was not expressed at early midgestational stages, showed its highest expression at the base of the diencephalon in the supraoptic area at embryonic day 11.5, and showed more expression in the subventricular zone at embryonic day 14.5. </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>Gross (2011) mapped the PAK3 gene to chromosome Xq23 based on an alignment of the PAK3 sequence (GenBank AF155651) with the genomic sequence (GRCh37).</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 affected members of an Australian family with a form of nonsyndromic X-linked intellectual developmental disorder (XLID30; 300558) found by Donnelly et al. (1996) to map to chromosome Xq21.3-q24, Allen et al. (1998) identified a mutation in the PAK3 gene (300142.0001). </p><p>In affected members of a French family with XLID reported by des Portes et al. (1997), Bienvenu et al. (2000) identified a mutation in the PAK3 gene (300142.0002). </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>Huang et al. (2011) noted that knockout of either Pak1 or Pak3 in mice results in no overt abnormality. They found that double knockout (DK) of both Pak1 and Pak3 resulted in mice that were born healthy, with normal brain size and structure. However, postnatal brain growth in DK mice was severely impaired due to reduced neuronal cell volume, reduced axonal and dendritic branching, and reduced synaptic density. Behaviorally, DK mice were hyperactive and anxious, and they exhibited a learning deficit compared with wildtype mice. These structural and functional deficits in DK mice were associated with abnormal electrophysiologic activity in hippocampus and enhanced synaptic cofilin (see 601442) activity. </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">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>5 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 30</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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PAK3, ARG419TER
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<br />
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|
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SNP: rs121434611,
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|
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ClinVar: RCV000012324, RCV000656321
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</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In affected males of an Australian family with nonsyndromic X-linked intellectual developmental disorder-30 (XLID30; 300558) reported by Donnelly et al. (1996), Allen et al. (1998) identified a 1255C-T transition in the PAK3 gene, resulting in an arg419-to-ter (R419X) substitution. The mutation was not identified in any unaffected males or more than 45 control individuals. When the MRX30 mutation was introduced into PAK3 cDNA and transfected into COS cells, the cDNA produced a stable, albeit truncated, protein with no measurable kinase activity. MRI studies of the more severely affected male with MRX30, who was microcephalic (although several other affected males were not), showed normal gross architecture of the cortex and hippocampus and other structures. Although more subtle defects in neuronal development could not be ruled out, MRI analysis suggested that PAK3 is not absolutely required for neuronal proliferation, migration, or cortical gyration. Therefore, the finding that the PAK3 mutation produces mental retardation may reflect a later requirement for PAK3 in axon outgrowth or function of the adult cortex. </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>
|
|
<span class="mim-font">
|
|
<strong>.0002 INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 30</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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PAK3, ARG67CYS
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<br />
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SNP: rs121434612,
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ClinVar: RCV000012325
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In affected males of a French family with nonsyndromic X-linked intellectual developmental disorder-30 (XLID30; 300558) reported by des Portes et al. (1997), Bienvenu et al. (2000) identified a 199C-T transition in exon 2 of the PAK3 gene, resulting in an arg67-to-cys (R67C) substitution in a polybasic region upstream of the CDC42/Rac interactive binding domain, and was predicted to affect GTPase binding. </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 INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 30</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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PAK3, ALA365GLU
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<br />
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SNP: rs121434613,
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ClinVar: RCV000012326, RCV003162241
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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 affected males of an Australian family with nonsyndromic X-linked intellectual developmental disorder-30 (XLID30; 300558), Gedeon et al. (2003) identified a 1094C-A transversion in exon 10 of the PAK3 gene, resulting in an ala365-to-glu (A365E) substitution. Affected males had borderline to mild mental retardation and most were able to function independently and hold menial jobs. Several patients had psychiatric disorders and some had relatively long ears. All carrier women had normal intelligence. </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 INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 30</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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PAK3, TRP446SER
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<br />
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SNP: rs121434614,
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ClinVar: RCV000012327
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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 5 males with intellectual developmental disorder-30 (XLID30; 300558) in a Finnish family, Peippo et al. (2007) identified a 1337G-C transversion in exon 7 of the PAK3 gene, resulting in a trp446-to-ser (W446S) substitution. Each mother of an affected male was found to be a carrier of the mutation. Peippo et al. (2007) examined X inactivation in carrier females by the methylation status of the polymorphic AR locus (313700). Skewed X inactivation was identified in 2 phenotypically normal females (90%:10%; 91%:9%) as well as in a borderline retarded female (100%:0%). The mutation was not found in 2 male relatives or in 200 unrelated Finnish controls. </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 INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 30</strong>
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</h4>
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<span class="mim-text-font">
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PAK3, IVS6DS, A-G, +4
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<br />
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SNP: rs1569398769,
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ClinVar: RCV000012328, RCV001257660, RCV003329230
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<p>In 3 affected males from a Tunisian family with X-linked intellectual developmental disorder-30 (XLID30; 300558), Rejeb et al. (2008) identified an A-to-G transition (276+4G-A) in intron 6 of the PAK3 gene, predicted to result in a novel donor splice site. RT-PCR analysis of patient RNA showed that the mutation resulted in a 4-bp insertion, frameshift, and premature termination at codon 128. The mutation was not identified in 200 control individuals. The phenotype was homogeneous, with microcephaly, oral motor dysfunction, and behavioral disturbances. X-inactivation studies showed completely skewed X inactivation in 2 female carriers. </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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</div>
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<ol>
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<li>
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<p class="mim-text-font">
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Allen, K. M., Gleeson, J. G., Bagrodia, S., Partington, M. W., MacMillan, J. C., Cerione, R. A., Mulley, J. C., Walsh, C. A.
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<strong>PAK3 mutation in nonsyndromic X-linked mental retardation.</strong>
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Nature Genet. 20: 25-30, 1998.
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[PubMed: 9731525]
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[Full Text: https://doi.org/10.1038/1675]
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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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Bagrodia, S., Taylor, S. J., Creasy, C. L., Chernoff, J., Cerione, R. A.
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<strong>Identification of a mouse p21Cdc/Rac activated kinase.</strong>
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J. Biol. Chem. 270: 22731-22737, 1995. Note: Erratum: J. Biol. Chem. 271: 1250 only, 1996.
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[PubMed: 7559398]
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[Full Text: https://doi.org/10.1074/jbc.270.39.22731]
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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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Bienvenu, T., des Portes, V., McDonell, N., Carrie, A., Zemni, R., Couvert, P., Ropers, H. H., Moraine, C., van Bokhoven, H., Fryns, J. P., Allen, K., Walsh, C. A., Boue, J., Kahn, A., Chelly, J., Beldjord, C.
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<strong>Missense mutation in PAK3, R67C, causes X-linked nonspecific mental retardation.</strong>
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Am. J. Med. Genet. 93: 294-298, 2000.
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[PubMed: 10946356]
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[Full Text: https://doi.org/10.1002/1096-8628(20000814)93:4<294::aid-ajmg8>3.0.co;2-f]
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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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Chelly, J.
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<strong>Breakthroughs in molecular and cellular mechanisms underlying X-linked mental retardation.</strong>
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Hum. Molec. Genet. 8: 1833-1838, 1999.
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[PubMed: 10469834]
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[Full Text: https://doi.org/10.1093/hmg/8.10.1833]
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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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des Portes, V., Soufir, N., Carrie, A., Billuart, P., Bienvenu, T., Vinet, M. C., Beldjord, C., Ponsot, G., Kahn, A., Boue, J., Chelly, J.
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<strong>Gene for nonspecific X-linked mental retardation (MRX 47) is located in Xq22.3-q24.</strong>
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Am. J. Med. Genet. 72: 324-328, 1997.
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[PubMed: 9332663]
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[Full Text: https://doi.org/10.1002/(sici)1096-8628(19971031)72:3<324::aid-ajmg14>3.0.co;2-v]
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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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Donnelly, A. J., Partington, M. W., Ryan, A. K., Mulley, J. C.
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<strong>Regional localisation of two non-specific X-linked mental retardation genes (MRX30 and MRX31).</strong>
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Am. J. Med. Genet. 64: 113-120, 1996.
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[PubMed: 8826460]
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[Full Text: https://doi.org/10.1002/(SICI)1096-8628(19960712)64:1<113::AID-AJMG19>3.0.CO;2-Q]
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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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Eswaran, J., Soundararajan, M., Kumar, R., Knapp, S.
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<strong>UnPAKing the class differences among p21-activated kinases.</strong>
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Trends Biochem. Sci. 33: 394-403, 2008.
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[PubMed: 18639460]
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[Full Text: https://doi.org/10.1016/j.tibs.2008.06.002]
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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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Gedeon, A. K., Nelson, J., Gecz, J., Mulley, J. C.
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<strong>X-linked mild non-syndromic mental retardation with neuropsychiatric problems and the missense mutation A365E in PAK3.</strong>
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Am. J. Med. Genet. 120A: 509-517, 2003.
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[PubMed: 12884430]
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[Full Text: https://doi.org/10.1002/ajmg.a.20131]
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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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Gross, M. B.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 5/9/2011.
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Huang, W., Zhou, Z., Asrar, S., Henkelman, M., Xie, W., Jia, Z.
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<strong>p21-activated kinases 1 and 3 control brain size through coordinating neuronal complexity and synaptic properties.</strong>
|
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Molec. Cell. Biol. 31: 388-403, 2011.
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[PubMed: 21115725]
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[Full Text: https://doi.org/10.1128/MCB.00969-10]
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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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Kohn, M., Steinbach, P., Hameister, H., Kehrer-Sawatzki, H.
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<strong>A comparative expression analysis of four MRX genes regulating intracellular signalling via small GTPases.</strong>
|
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Europ. J. Hum. Genet. 12: 29-37, 2004.
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[PubMed: 14673471]
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[Full Text: https://doi.org/10.1038/sj.ejhg.5201085]
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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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Manser, E., Chong, C., Zhao, Z. S., Leung, T., Michael, G., Hall, C., Lim, L.
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<strong>Molecular cloning of a new member of the p21-Cdc42/Rac-activated kinase (PAK) family.</strong>
|
|
J. Biol. Chem. 270: 25070-25078, 1995.
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[PubMed: 7559638]
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[Full Text: https://doi.org/10.1074/jbc.270.42.25070]
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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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Manser, E., Leung, T., Salihuddin, H., Zhao, Z., Lim, L.
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<strong>A brain serine/threonine protein kinase activated by Cdc42 and Rac1.</strong>
|
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Nature 367: 40-46, 1994.
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[PubMed: 8107774]
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[Full Text: https://doi.org/10.1038/367040a0]
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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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Peippo, M., Koivisto, A. M., Sarkamo, T., Sipponen, M., von Koskull, H., Ylisaukko-oja, T., Rehnstrom, K., Froyen, G., Ignatius, J., Jarvela, I.
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<strong>PAK3 related mental disability: further characterization of the phenotype.</strong>
|
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Am. J. Med. Genet. 143A: 2406-2416, 2007.
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[PubMed: 17853471]
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[Full Text: https://doi.org/10.1002/ajmg.a.31956]
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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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Rejeb, I., Saillour, Y., Castelnau, L., Julien, C., Bienvenu, T., Taga, P., Chaabouni, H., Chelly, J., Jemaa, L. B., Bahi-Buisson, N.
|
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<strong>A novel splice mutation in PAK3 gene underlying mental retardation with neuropsychiatric features.</strong>
|
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Europ. J. Hum. Genet. 16: 1358-1363, 2008.
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[PubMed: 18523455]
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[Full Text: https://doi.org/10.1038/ejhg.2008.103]
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</p>
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<li>
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<p class="mim-text-font">
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Zhao, Z., Manser, E.
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<strong>PAK and other Rho-associated kinases--effectors with surprisingly diverse mechanisms of regulation.</strong>
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Biochem. J. 386: 201-214, 2005.
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[PubMed: 15548136]
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[Full Text: https://doi.org/10.1042/BJ20041638]
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</ol>
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<br />
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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Contributors:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Patricia A. Hartz - updated : 12/22/2011<br>Matthew B. Gross - updated : 5/9/2011<br>Cassandra L. Kniffin - updated : 8/31/2009<br>Kelly A. Przylepa - updated : 4/1/2008<br>Cassandra L. Kniffin - updated : 10/6/2005<br>Marla J. F. O'Neill - updated : 5/6/2004<br>Victor A. McKusick - updated : 10/12/1999
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<span class="mim-text-font">
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Victor A. McKusick : 8/28/1998
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carol : 08/20/2021<br>mcolton : 05/21/2014<br>carol : 9/12/2013<br>terry : 6/6/2012<br>mgross : 1/9/2012<br>terry : 12/22/2011<br>mgross : 5/9/2011<br>wwang : 9/16/2009<br>ckniffin : 8/31/2009<br>carol : 4/4/2008<br>terry : 4/1/2008<br>carol : 10/7/2005<br>ckniffin : 10/6/2005<br>carol : 5/6/2004<br>carol : 5/6/2004<br>terry : 5/6/2004<br>alopez : 3/17/2004<br>terry : 4/28/2003<br>alopez : 3/11/2003<br>mgross : 5/31/2000<br>carol : 10/12/1999<br>terry : 6/9/1999<br>mgross : 3/16/1999<br>alopez : 8/28/1998
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