3072 lines
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Entry
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- *608170 - DEAD-BOX HELICASE 41; DDX41
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*608170</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="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/608170">Table View</a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</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=ENSG00000183258;t=ENST00000330503" 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=51428" 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=608170" 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 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=ENSG00000183258;t=ENST00000330503" 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_001321732,NM_001321830,NM_016222" 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_016222" 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=608170" 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=10490&isoform_id=10490_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/DDX41" 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/6118555,6808033,7022398,14042692,15930065,20532370,21071032,34364998,51981728,62896755,119605383,119605384,119605385,119605386,119605387,189067937,193787208,1012431804,1012431806" 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/Q9UJV9" 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=51428" 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=ENSG00000183258;t=ENST00000330503" 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=DDX41" 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=DDX41" 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+51428" 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/DDX41" 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:51428" 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/51428" 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=chr5&hgg_gene=ENST00000330503.12&hgg_start=177511577&hgg_end=177516961&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:18674" 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:18674" 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=608170[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=608170[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/DDX41/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/ENSG00000183258" 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.gwascentral.org/search?q=DDX41" 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=DDX41" 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=DDX41&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/PA134908862" 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:18674" 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/FBgn0015331.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:1920185" 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/DDX41#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:1920185" 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/51428/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=51428" 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=WBGene00019245;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-030131-1927" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:51428" 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=DDX41&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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608170
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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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DEAD-BOX HELICASE 41; DDX41
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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DEAD/H-BOX 41<br />
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ABSTRAKT, DROSOPHILA, HOMOLOG OF; ABS
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=DDX41" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">DDX41</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/5/814?start=-3&limit=10&highlight=814">5q35.3</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr5:177511577-177516961&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'})">5:177,511,577-177,516,961</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="geneMap" class="mim-anchor"></a>
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<div style="margin-bottom: 10px;">
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<span class="h4 mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
|
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<a href="/geneMap/5/814?start=-3&limit=10&highlight=814">
|
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5q35.3
|
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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{Myeloproliferative/lymphoproliferative neoplasms, familial (multiple types), susceptibility to}
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</span>
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</td>
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<td>
|
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<span class="mim-font">
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<a href="/entry/616871"> 616871 </a>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
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</button>
|
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<ul class="dropdown-menu" style="width: 17em;">
|
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<li><a href="/graph/linear/608170" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/608170" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
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<strong>TEXT</strong>
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</span>
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</span>
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</h4>
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<div>
|
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<a id="description" class="mim-anchor"></a>
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<p>The DDX41 gene encodes an RNA helicase. Evidence suggests that it also acts as a tumor suppressor gene (summary by <a href="#3" class="mim-tip-reference" title="Lewinsohn, M., Brown, A. L., Weinel, L. M., Phung, C., Rafidi, G., Lee, M. K., Schreiber, A. W., Feng, J., Babic, M., Chong, C.-E., Lee, Y., Yong, A., and 18 others. <strong>Novel germ line DDX41 mutations define families with a lower age of MDS/AML onset and lymphoid malignancies.</strong> Blood 127: 1017-1023, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26712909/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26712909</a>] [<a href="https://doi.org/10.1182/blood-2015-10-676098" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26712909">Lewinsohn et al., 2016</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26712909" 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="#2" class="mim-tip-reference" title="Irion, U., Leptin, M. <strong>Developmental and cell biological functions of the Drosophila DEAD-box protein Abstrakt.</strong> Curr. Biol. 9: 1373-1381, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10607561/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10607561</a>] [<a href="https://doi.org/10.1016/s0960-9822(00)80082-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10607561">Irion and Leptin (1999)</a> cloned DDX41, which they called ABS, by PCR of a HeLa cell cDNA library. The deduced 621-amino acid protein shares 64% identity with the Drosophila abstrakt protein, including 100% identity in 7 of the 8 motifs characteristic of DEAD box proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10607561" 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="Polprasert, C., Schulze, I., Sekeres, M. A., Makishima, H., Przychodzen, B., Hosono, N., Singh, J., Padgett, R. A., Gu, X., Phillips, J. G., Clemente, M., Parker, Y., and 24 others. <strong>Inherited and somatic defects in DDX41 in myeloid neoplasms.</strong> Cancer Cell 27: 658-670, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25920683/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25920683</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25920683[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ccell.2015.03.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25920683">Polprasert et al. (2015)</a> reported expression of the DDX41 gene in CD14+, CD33+, and CD34+ myeloid cells, consistent with a function in hematopoiesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25920683" 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="#1" class="mim-tip-reference" title="Gross, M. B. <strong>Personal Communication.</strong> Baltimore, Md. 3/23/2016."None>Gross (2016)</a> mapped the DDX41 gene to chromosome 5q35.3 based on an alignment of the DDX41 sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=BC015476" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">BC015476</a>) with the genomic sequence (GRCh38).</p>
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<p>Using immunoprecipitation experiments, <a href="#4" class="mim-tip-reference" title="Polprasert, C., Schulze, I., Sekeres, M. A., Makishima, H., Przychodzen, B., Hosono, N., Singh, J., Padgett, R. A., Gu, X., Phillips, J. G., Clemente, M., Parker, Y., and 24 others. <strong>Inherited and somatic defects in DDX41 in myeloid neoplasms.</strong> Cancer Cell 27: 658-670, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25920683/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25920683</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25920683[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ccell.2015.03.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25920683">Polprasert et al. (2015)</a> found that DDX41 interacted with several spliceosomal proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25920683" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In affected members of 7 unrelated families with multiple types of familial myeloproliferative/lymphoproliferative neoplasms (MPLPF; <a href="/entry/616871">616871</a>), <a href="#4" class="mim-tip-reference" title="Polprasert, C., Schulze, I., Sekeres, M. A., Makishima, H., Przychodzen, B., Hosono, N., Singh, J., Padgett, R. A., Gu, X., Phillips, J. G., Clemente, M., Parker, Y., and 24 others. <strong>Inherited and somatic defects in DDX41 in myeloid neoplasms.</strong> Cancer Cell 27: 658-670, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25920683/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25920683</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25920683[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ccell.2015.03.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25920683">Polprasert et al. (2015)</a> identified a heterozygous germline mutation in the DDX41 gene (see, e.g., <a href="#0001">608170.0001</a>; <a href="#0003">608170.0003</a>). Most of the patients had a recurrent germline truncating mutation (Asp140fs; <a href="#0001">608170.0001</a>). About half of the patients also carried a somatic heterozygous missense mutation in the DDX41 gene (R525H; <a href="#0002">608170.0002</a>) on the other allele. This missense mutation was shown to be a hypomorphic allele. Subsequent targeted sequencing of the DDX41 gene in 1,034 patients with MDS/AML identified 16 with heterozygous germline and/or somatic DDX41 mutations, including Asp140fs and R525H. Two of these patients were diagnosed with chromosome 5q- syndrome (<a href="/entry/153550">153550</a>). Overall, DDX41 mutations and deletions occurred more frequently in patients with advanced MDS and in patients with AML, and were associated with inferior overall survival compared to patients without DDX41 genetic alterations. Knockdown of the DDX41 gene in human hematopoietic cells resulted in enhanced proliferation, enhanced colony formation, and increased sensitivity to growth factor stimuli compared to controls. Knockdown of DDX41 also impaired cell differentiation and increased resistance to apoptosis. Forced expression of the gene resulted in growth inhibition; these overall findings suggested that DDX41 has tumor suppressor functions. In vitro functional expression studies indicated that the R525H mutation interfered with the ability of DDX41 to interact with several major spliceosomal components, and DDX41-deficient cells showed multiple splicing defects, including exon skipping in the ZMYM2 gene (<a href="/entry/602221">602221</a>). Deletions of chromosome 5q involving the DDX41 gene were found in 6% of all cases and in 26% of the del(5q) cases; these resulted in decreased DDX41 mRNA levels, suggesting that some cases of 5q deletion syndrome may result from deletion of the DDX41 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25920683" 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 individuals from 10 unrelated families with MPLPF, <a href="#3" class="mim-tip-reference" title="Lewinsohn, M., Brown, A. L., Weinel, L. M., Phung, C., Rafidi, G., Lee, M. K., Schreiber, A. W., Feng, J., Babic, M., Chong, C.-E., Lee, Y., Yong, A., and 18 others. <strong>Novel germ line DDX41 mutations define families with a lower age of MDS/AML onset and lymphoid malignancies.</strong> Blood 127: 1017-1023, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26712909/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26712909</a>] [<a href="https://doi.org/10.1182/blood-2015-10-676098" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26712909">Lewinsohn et al. (2016)</a> identified germline heterozygous mutations in the DDX41 gene (see, e.g., <a href="#0001">608170.0001</a>-<a href="#0002">608170.0002</a>; <a href="#0004">608170.0004</a>-<a href="#0006">608170.0006</a>). Lymphoma was diagnosed in affected members from only 1 family (CCB 25476) with a missense mutation (R164W; <a href="#0006">608170.0006</a>). In some cases, studies of patient cells showed deleterious effects of the mutation on protein expression, but functional studies of the variants were not performed. In the entire cohort, the majority of mutation carriers had normal peripheral blood counts well into adulthood, suggesting that haploinsufficiency of DDX41 is sufficient for normal baseline hematopoiesis. The authors stated that 9 of the families were ascertained from a cohort of 289 families with inherited hematologic malignancies who underwent whole-exome sequencing, panel-based next-generation sequencing, or targeted sequencing of the DDX41 gene; they thus accounted for about 3% of families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26712909" 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>Using temperature-sensitive alleles, <a href="#2" class="mim-tip-reference" title="Irion, U., Leptin, M. <strong>Developmental and cell biological functions of the Drosophila DEAD-box protein Abstrakt.</strong> Curr. Biol. 9: 1373-1381, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10607561/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10607561</a>] [<a href="https://doi.org/10.1016/s0960-9822(00)80082-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10607561">Irion and Leptin (1999)</a> determined that abstrakt is essential for survival at all stages of the fly life cycle. Mutants showed specific defects in many developmental processes, including cell shape changes, localization of RNA, and apoptosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10607561" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs762890562 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs762890562;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs762890562?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs762890562" 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=rs762890562" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In affected members of 6 unrelated families with multiple types of familial myeloproliferative/lymphoproliferative neoplasms (MPLPF; <a href="/entry/616871">616871</a>), <a href="#4" class="mim-tip-reference" title="Polprasert, C., Schulze, I., Sekeres, M. A., Makishima, H., Przychodzen, B., Hosono, N., Singh, J., Padgett, R. A., Gu, X., Phillips, J. G., Clemente, M., Parker, Y., and 24 others. <strong>Inherited and somatic defects in DDX41 in myeloid neoplasms.</strong> Cancer Cell 27: 658-670, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25920683/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25920683</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25920683[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ccell.2015.03.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25920683">Polprasert et al. (2015)</a> identified a heterozygous germline 4-bp insertion (c.419insGATG) in the DDX41 gene, resulting in a frameshift (Asp140fs). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not found in 200 in-house controls. It was found in 1 of 12,518 alleles in the Exome Sequencing Project database. About half of the patients also carried a somatic heterozygous c.1574G-A transition in the DDX41 gene, resulting in an arg525-to-his (R525H; <a href="#0002">608170.0002</a>) substitution at a conserved residue in an ATP binding domain, that was confirmed to be on the other allele. A heterozygous germline Asp140fs mutation was also found in 6 additional unrelated patients with sporadic myeloproliferative neoplasms. One of these patients also carried the somatic R525H mutation. These patients were part of a large cohort of 1,034 individuals with MDS/AML. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25920683" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 4 patients from 3 unrelated families with MPLPF, <a href="#3" class="mim-tip-reference" title="Lewinsohn, M., Brown, A. L., Weinel, L. M., Phung, C., Rafidi, G., Lee, M. K., Schreiber, A. W., Feng, J., Babic, M., Chong, C.-E., Lee, Y., Yong, A., and 18 others. <strong>Novel germ line DDX41 mutations define families with a lower age of MDS/AML onset and lymphoid malignancies.</strong> Blood 127: 1017-1023, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26712909/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26712909</a>] [<a href="https://doi.org/10.1182/blood-2015-10-676098" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26712909">Lewinsohn et al. (2016)</a> identified a heterozygous germline 4-bp insertion (c.419insGATG, NM_016222.2) in the DDX41 gene, resulting in a frameshift and premature termination (Asp140fsTer2). One of the patients carried a somatic R525H mutation on the other allele. A fourth family (family UoC 127) with this mutation was reported in the supplementary material. There was evidence of incomplete penetrance in 2 of the families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26712909" 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">rs869312828 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs869312828;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=rs869312828" 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=rs869312828" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 3 members of a family (CCB 31379) with MPLPF, <a href="#3" class="mim-tip-reference" title="Lewinsohn, M., Brown, A. L., Weinel, L. M., Phung, C., Rafidi, G., Lee, M. K., Schreiber, A. W., Feng, J., Babic, M., Chong, C.-E., Lee, Y., Yong, A., and 18 others. <strong>Novel germ line DDX41 mutations define families with a lower age of MDS/AML onset and lymphoid malignancies.</strong> Blood 127: 1017-1023, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26712909/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26712909</a>] [<a href="https://doi.org/10.1182/blood-2015-10-676098" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26712909">Lewinsohn et al. (2016)</a> identified a heterozygous germline c.1574G-A transition (c.1574G-A, NM_016222.2) in the DDX41 gene, resulting in an arg525-to-his (R525H) substitution. The patients were diagnosed between 44 and 56 years of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26712909" 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>For discussion of the somatic c.1574G-A transition in the DDX41 gene, resulting in an arg525-to-his (R525H) substitution at a conserved residue in an ATP binding domain, that was found in compound heterozygous state in individuals with multiple types of familial myeloproliferative/lymphoproliferative neoplasms (MPLPF; <a href="/entry/616871">616871</a>) by <a href="#4" class="mim-tip-reference" title="Polprasert, C., Schulze, I., Sekeres, M. A., Makishima, H., Przychodzen, B., Hosono, N., Singh, J., Padgett, R. A., Gu, X., Phillips, J. G., Clemente, M., Parker, Y., and 24 others. <strong>Inherited and somatic defects in DDX41 in myeloid neoplasms.</strong> Cancer Cell 27: 658-670, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25920683/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25920683</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25920683[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ccell.2015.03.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25920683">Polprasert et al. (2015)</a>, see (<a href="#0001">608170.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25920683" 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="Polprasert, C., Schulze, I., Sekeres, M. A., Makishima, H., Przychodzen, B., Hosono, N., Singh, J., Padgett, R. A., Gu, X., Phillips, J. G., Clemente, M., Parker, Y., and 24 others. <strong>Inherited and somatic defects in DDX41 in myeloid neoplasms.</strong> Cancer Cell 27: 658-670, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25920683/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25920683</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25920683[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ccell.2015.03.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25920683">Polprasert et al. (2015)</a> found a heterozygous somatic R525X mutation in 6 of 1,034 unrelated patients with sporadic occurrence of MDS/AML. One of these patients carried a germline Asp140fs (<a href="#0001">608170.0001</a>) on the other allele and another had a germline deletion of 5q including the DDX41 gene (see also <a href="/entry/153550">153550</a>). In vitro functional expression studies indicated that the R525H mutation interfered with the ability of DDX41 to interact with several major spliceosomal components. <a href="#4" class="mim-tip-reference" title="Polprasert, C., Schulze, I., Sekeres, M. A., Makishima, H., Przychodzen, B., Hosono, N., Singh, J., Padgett, R. A., Gu, X., Phillips, J. G., Clemente, M., Parker, Y., and 24 others. <strong>Inherited and somatic defects in DDX41 in myeloid neoplasms.</strong> Cancer Cell 27: 658-670, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25920683/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25920683</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25920683[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ccell.2015.03.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25920683">Polprasert et al. (2015)</a> concluded that it was a hypomorphic allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25920683" 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 MYELOPROLIFERATIVE/LYMPHOPROLIFERATIVE NEOPLASMS, FAMILIAL (MULTIPLE TYPES), SUSCEPTIBILITY TO</strong>
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<p>In a pair of twin brothers with multiple types of familial myeloproliferative/lymphoproliferative neoplasms (MPLPF; <a href="/entry/616871">616871</a>), <a href="#4" class="mim-tip-reference" title="Polprasert, C., Schulze, I., Sekeres, M. A., Makishima, H., Przychodzen, B., Hosono, N., Singh, J., Padgett, R. A., Gu, X., Phillips, J. G., Clemente, M., Parker, Y., and 24 others. <strong>Inherited and somatic defects in DDX41 in myeloid neoplasms.</strong> Cancer Cell 27: 658-670, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25920683/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25920683</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25920683[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ccell.2015.03.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25920683">Polprasert et al. (2015)</a> identified a germline heterozygous c.1187T-C transition (c.1187T-C, NM_016222.2) in the DDX41 gene, resulting in an ile396-to-thr (I396T) substitution at a conserved residue. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not found in the 1000 Genomes Project or Exome Sequencing Project databases or in 200 in-house controls. Each brother also carried a somatic R525X mutation (<a href="#0002">608170.0002</a>) on the other allele; one also had a somatic variant in the JAK2 gene (V617F; <a href="/entry/147796#0001">147796.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25920683" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a man (family UoC 154) with familial myeloproliferative/lymphoproliferative neoplasms (MPLPF; <a href="/entry/616871">616871</a>), <a href="#3" class="mim-tip-reference" title="Lewinsohn, M., Brown, A. L., Weinel, L. M., Phung, C., Rafidi, G., Lee, M. K., Schreiber, A. W., Feng, J., Babic, M., Chong, C.-E., Lee, Y., Yong, A., and 18 others. <strong>Novel germ line DDX41 mutations define families with a lower age of MDS/AML onset and lymphoid malignancies.</strong> Blood 127: 1017-1023, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26712909/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26712909</a>] [<a href="https://doi.org/10.1182/blood-2015-10-676098" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26712909">Lewinsohn et al. (2016)</a> identified a germline heterozygous del/ins mutation (c.435-2_435-1delAGinsCA, NM_016222.2) in the splice acceptor site of exon 6 of the DDX41 gene. Analysis of patient cells showed the presence of aberrant mRNA species that were predicted to result in frameshifts and prematurely terminated proteins. There was evidence of incomplete penetrance in this family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26712909" 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>.0005 MYELOPROLIFERATIVE/LYMPHOPROLIFERATIVE NEOPLASMS, FAMILIAL (MULTIPLE TYPES), SUSCEPTIBILITY TO</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs141601766 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs141601766;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs141601766?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs141601766" 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=rs141601766" 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=RCV000210251 OR RCV000519179 OR RCV001256169 OR RCV001256171 OR RCV003907781 OR RCV004975331" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000210251, RCV000519179, RCV001256169, RCV001256171, RCV003907781, RCV004975331" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000210251...</a>
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<p>In affected members of 2 unrelated families (CCB 20432 and UoC 236) with familial myeloproliferative/lymphoproliferative neoplasms (MPLPF; <a href="/entry/616871">616871</a>), <a href="#3" class="mim-tip-reference" title="Lewinsohn, M., Brown, A. L., Weinel, L. M., Phung, C., Rafidi, G., Lee, M. K., Schreiber, A. W., Feng, J., Babic, M., Chong, C.-E., Lee, Y., Yong, A., and 18 others. <strong>Novel germ line DDX41 mutations define families with a lower age of MDS/AML onset and lymphoid malignancies.</strong> Blood 127: 1017-1023, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26712909/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26712909</a>] [<a href="https://doi.org/10.1182/blood-2015-10-676098" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26712909">Lewinsohn et al. (2016)</a> identified a germline heterozygous c.3G-A transition (c.3G-A, NM_016222.2) in the DDX41 gene, resulting in a met1-to-ile (M1I) substitution in the initiation codon. The mutation was predicted to result in a loss of function. There was evidence of incomplete penetrance in both families. In 1 family, a carrier of the mutation did not have a hematologic malignancy, but did have a history inflammatory-related disorders, including sarcoidosis and eczema. Analysis of patient cells showed that the mutation resulted in the production of a smaller protein from use of an alternative translation initiation site. The smaller isoform showed reduced nuclear localization, consistent with the loss of a predicted nuclear localization signal. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26712909" 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>.0006 MYELOPROLIFERATIVE/LYMPHOPROLIFERATIVE NEOPLASMS, FAMILIAL (MULTIPLE TYPES), SUSCEPTIBILITY TO</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs142143752 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs142143752;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs142143752?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs142143752" 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=rs142143752" 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=RCV000210264 OR RCV001818508 OR RCV004975332" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000210264, RCV001818508, RCV004975332" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000210264...</a>
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<p>In affected members of a family (CCB 25476) of Dutch-Sri Lankan descent with familial myeloproliferative/lymphoproliferative neoplasms (MPLPF; <a href="/entry/616871">616871</a>), <a href="#3" class="mim-tip-reference" title="Lewinsohn, M., Brown, A. L., Weinel, L. M., Phung, C., Rafidi, G., Lee, M. K., Schreiber, A. W., Feng, J., Babic, M., Chong, C.-E., Lee, Y., Yong, A., and 18 others. <strong>Novel germ line DDX41 mutations define families with a lower age of MDS/AML onset and lymphoid malignancies.</strong> Blood 127: 1017-1023, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26712909/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26712909</a>] [<a href="https://doi.org/10.1182/blood-2015-10-676098" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26712909">Lewinsohn et al. (2016)</a> identified a germline heterozygous c.490C-T transition (c.490C-T, NM_016222.2) in the DDX41 gene, resulting in an arg164-to-trp (R164W) substitution at a highly conserved residue adjacent to the Q motif. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the 1000 Genomes Project database; it was found at a very low frequency (0.014%) in the ExAC database. There was evidence of incomplete penetrance. The 4 patients with a confirmed mutation had lymphoma, and there was a family history of multiple myeloma in previous generations. Several variant-carrying family members had inflammatory-mediated disorders without overt hematologic malignancies. Functional studies of the variant were not performed, but it was predicted to affect DDX41 helicase activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26712909" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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<a id="Gross2016" class="mim-anchor"></a>
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Gross, M. B.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 3/23/2016.
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Irion, U., Leptin, M.
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<strong>Developmental and cell biological functions of the Drosophila DEAD-box protein Abstrakt.</strong>
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Curr. Biol. 9: 1373-1381, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10607561/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10607561</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10607561" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0960-9822(00)80082-2" target="_blank">Full Text</a>]
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Lewinsohn, M., Brown, A. L., Weinel, L. M., Phung, C., Rafidi, G., Lee, M. K., Schreiber, A. W., Feng, J., Babic, M., Chong, C.-E., Lee, Y., Yong, A., and 18 others.
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<strong>Novel germ line DDX41 mutations define families with a lower age of MDS/AML onset and lymphoid malignancies.</strong>
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Blood 127: 1017-1023, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26712909/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26712909</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26712909" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1182/blood-2015-10-676098" target="_blank">Full Text</a>]
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<a id="Polprasert2015" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Polprasert, C., Schulze, I., Sekeres, M. A., Makishima, H., Przychodzen, B., Hosono, N., Singh, J., Padgett, R. A., Gu, X., Phillips, J. G., Clemente, M., Parker, Y., and 24 others.
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<strong>Inherited and somatic defects in DDX41 in myeloid neoplasms.</strong>
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Cancer Cell 27: 658-670, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25920683/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25920683</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25920683[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25920683" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ccell.2015.03.017" target="_blank">Full Text</a>]
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<span class="mim-text-font">
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Matthew B. Gross - updated : 03/23/2016
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Cassandra L. Kniffin - updated : 3/22/2016
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Patricia A. Hartz : 10/14/2003
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alopez : 03/16/2023
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mgross : 07/14/2020<br>carol : 10/04/2016<br>mgross : 03/23/2016<br>carol : 3/22/2016<br>ckniffin : 3/22/2016<br>mgross : 10/14/2003
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<strong>*</strong> 608170
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DEAD-BOX HELICASE 41; DDX41
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DEAD/H-BOX 41<br />
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ABSTRAKT, DROSOPHILA, HOMOLOG OF; ABS
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Cytogenetic location: 5q35.3
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<span class="small">(from NCBI)</span>
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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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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5q35.3
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</span>
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</td>
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<td>
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<span class="mim-font">
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{Myeloproliferative/lymphoproliferative neoplasms, familial (multiple types), susceptibility to}
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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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616871
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The DDX41 gene encodes an RNA helicase. Evidence suggests that it also acts as a tumor suppressor gene (summary by Lewinsohn et al., 2016). </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>Irion and Leptin (1999) cloned DDX41, which they called ABS, by PCR of a HeLa cell cDNA library. The deduced 621-amino acid protein shares 64% identity with the Drosophila abstrakt protein, including 100% identity in 7 of the 8 motifs characteristic of DEAD box proteins. </p><p>Polprasert et al. (2015) reported expression of the DDX41 gene in CD14+, CD33+, and CD34+ myeloid cells, consistent with a function in hematopoiesis. </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 (2016) mapped the DDX41 gene to chromosome 5q35.3 based on an alignment of the DDX41 sequence (GenBank BC015476) with the genomic sequence (GRCh38).</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Using immunoprecipitation experiments, Polprasert et al. (2015) found that DDX41 interacted with several spliceosomal proteins. </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 7 unrelated families with multiple types of familial myeloproliferative/lymphoproliferative neoplasms (MPLPF; 616871), Polprasert et al. (2015) identified a heterozygous germline mutation in the DDX41 gene (see, e.g., 608170.0001; 608170.0003). Most of the patients had a recurrent germline truncating mutation (Asp140fs; 608170.0001). About half of the patients also carried a somatic heterozygous missense mutation in the DDX41 gene (R525H; 608170.0002) on the other allele. This missense mutation was shown to be a hypomorphic allele. Subsequent targeted sequencing of the DDX41 gene in 1,034 patients with MDS/AML identified 16 with heterozygous germline and/or somatic DDX41 mutations, including Asp140fs and R525H. Two of these patients were diagnosed with chromosome 5q- syndrome (153550). Overall, DDX41 mutations and deletions occurred more frequently in patients with advanced MDS and in patients with AML, and were associated with inferior overall survival compared to patients without DDX41 genetic alterations. Knockdown of the DDX41 gene in human hematopoietic cells resulted in enhanced proliferation, enhanced colony formation, and increased sensitivity to growth factor stimuli compared to controls. Knockdown of DDX41 also impaired cell differentiation and increased resistance to apoptosis. Forced expression of the gene resulted in growth inhibition; these overall findings suggested that DDX41 has tumor suppressor functions. In vitro functional expression studies indicated that the R525H mutation interfered with the ability of DDX41 to interact with several major spliceosomal components, and DDX41-deficient cells showed multiple splicing defects, including exon skipping in the ZMYM2 gene (602221). Deletions of chromosome 5q involving the DDX41 gene were found in 6% of all cases and in 26% of the del(5q) cases; these resulted in decreased DDX41 mRNA levels, suggesting that some cases of 5q deletion syndrome may result from deletion of the DDX41 gene. </p><p>In affected individuals from 10 unrelated families with MPLPF, Lewinsohn et al. (2016) identified germline heterozygous mutations in the DDX41 gene (see, e.g., 608170.0001-608170.0002; 608170.0004-608170.0006). Lymphoma was diagnosed in affected members from only 1 family (CCB 25476) with a missense mutation (R164W; 608170.0006). In some cases, studies of patient cells showed deleterious effects of the mutation on protein expression, but functional studies of the variants were not performed. In the entire cohort, the majority of mutation carriers had normal peripheral blood counts well into adulthood, suggesting that haploinsufficiency of DDX41 is sufficient for normal baseline hematopoiesis. The authors stated that 9 of the families were ascertained from a cohort of 289 families with inherited hematologic malignancies who underwent whole-exome sequencing, panel-based next-generation sequencing, or targeted sequencing of the DDX41 gene; they thus accounted for about 3% of families. </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>Using temperature-sensitive alleles, Irion and Leptin (1999) determined that abstrakt is essential for survival at all stages of the fly life cycle. Mutants showed specific defects in many developmental processes, including cell shape changes, localization of RNA, and apoptosis. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>ALLELIC VARIANTS</strong>
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</span>
|
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<strong>6 Selected Examples):</strong>
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</span>
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</h4>
|
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<div>
|
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<p />
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0001 MYELOPROLIFERATIVE/LYMPHOPROLIFERATIVE NEOPLASMS, FAMILIAL (MULTIPLE TYPES), SUSCEPTIBILITY TO</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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DDX41, 4-BP INS, 419GATG
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<br />
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SNP: rs762890562,
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gnomAD: rs762890562,
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ClinVar: RCV000193600, RCV000210272, RCV001008139, RCV004751355, RCV004975322
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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 members of 6 unrelated families with multiple types of familial myeloproliferative/lymphoproliferative neoplasms (MPLPF; 616871), Polprasert et al. (2015) identified a heterozygous germline 4-bp insertion (c.419insGATG) in the DDX41 gene, resulting in a frameshift (Asp140fs). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not found in 200 in-house controls. It was found in 1 of 12,518 alleles in the Exome Sequencing Project database. About half of the patients also carried a somatic heterozygous c.1574G-A transition in the DDX41 gene, resulting in an arg525-to-his (R525H; 608170.0002) substitution at a conserved residue in an ATP binding domain, that was confirmed to be on the other allele. A heterozygous germline Asp140fs mutation was also found in 6 additional unrelated patients with sporadic myeloproliferative neoplasms. One of these patients also carried the somatic R525H mutation. These patients were part of a large cohort of 1,034 individuals with MDS/AML. </p><p>In 4 patients from 3 unrelated families with MPLPF, Lewinsohn et al. (2016) identified a heterozygous germline 4-bp insertion (c.419insGATG, NM_016222.2) in the DDX41 gene, resulting in a frameshift and premature termination (Asp140fsTer2). One of the patients carried a somatic R525H mutation on the other allele. A fourth family (family UoC 127) with this mutation was reported in the supplementary material. There was evidence of incomplete penetrance in 2 of the families. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0002 MYELOPROLIFERATIVE/LYMPHOPROLIFERATIVE NEOPLASMS, FAMILIAL (MULTIPLE TYPES), SUSCEPTIBILITY TO</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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DDX41, ARG525HIS
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<br />
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|
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SNP: rs869312828,
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ClinVar: RCV000210250, RCV002288840
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</span>
|
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</div>
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|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 members of a family (CCB 31379) with MPLPF, Lewinsohn et al. (2016) identified a heterozygous germline c.1574G-A transition (c.1574G-A, NM_016222.2) in the DDX41 gene, resulting in an arg525-to-his (R525H) substitution. The patients were diagnosed between 44 and 56 years of age. </p><p>For discussion of the somatic c.1574G-A transition in the DDX41 gene, resulting in an arg525-to-his (R525H) substitution at a conserved residue in an ATP binding domain, that was found in compound heterozygous state in individuals with multiple types of familial myeloproliferative/lymphoproliferative neoplasms (MPLPF; 616871) by Polprasert et al. (2015), see (608170.0001). </p><p>Polprasert et al. (2015) found a heterozygous somatic R525X mutation in 6 of 1,034 unrelated patients with sporadic occurrence of MDS/AML. One of these patients carried a germline Asp140fs (608170.0001) on the other allele and another had a germline deletion of 5q including the DDX41 gene (see also 153550). In vitro functional expression studies indicated that the R525H mutation interfered with the ability of DDX41 to interact with several major spliceosomal components. Polprasert et al. (2015) concluded that it was a hypomorphic allele. </p>
|
|
</span>
|
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 MYELOPROLIFERATIVE/LYMPHOPROLIFERATIVE NEOPLASMS, FAMILIAL (MULTIPLE TYPES), SUSCEPTIBILITY TO</strong>
|
|
</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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DDX41, ILE396THR
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<br />
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SNP: rs747072227,
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gnomAD: rs747072227,
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ClinVar: RCV000210262, RCV001553497
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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 a pair of twin brothers with multiple types of familial myeloproliferative/lymphoproliferative neoplasms (MPLPF; 616871), Polprasert et al. (2015) identified a germline heterozygous c.1187T-C transition (c.1187T-C, NM_016222.2) in the DDX41 gene, resulting in an ile396-to-thr (I396T) substitution at a conserved residue. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not found in the 1000 Genomes Project or Exome Sequencing Project databases or in 200 in-house controls. Each brother also carried a somatic R525X mutation (608170.0002) on the other allele; one also had a somatic variant in the JAK2 gene (V617F; 147796.0001). </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>.0004 MYELOPROLIFERATIVE/LYMPHOPROLIFERATIVE NEOPLASMS, FAMILIAL (MULTIPLE TYPES), SUSCEPTIBILITY TO</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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|
|
DDX41, EX6DEL
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<br />
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SNP: rs869320762,
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ClinVar: RCV000210273, RCV001815218
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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 a man (family UoC 154) with familial myeloproliferative/lymphoproliferative neoplasms (MPLPF; 616871), Lewinsohn et al. (2016) identified a germline heterozygous del/ins mutation (c.435-2_435-1delAGinsCA, NM_016222.2) in the splice acceptor site of exon 6 of the DDX41 gene. Analysis of patient cells showed the presence of aberrant mRNA species that were predicted to result in frameshifts and prematurely terminated proteins. There was evidence of incomplete penetrance in this family. </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>.0005 MYELOPROLIFERATIVE/LYMPHOPROLIFERATIVE NEOPLASMS, FAMILIAL (MULTIPLE TYPES), SUSCEPTIBILITY TO</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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DDX41, MET1ILE
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<br />
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SNP: rs141601766,
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gnomAD: rs141601766,
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ClinVar: RCV000210251, RCV000519179, RCV001256169, RCV001256171, RCV003907781, RCV004975331
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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 members of 2 unrelated families (CCB 20432 and UoC 236) with familial myeloproliferative/lymphoproliferative neoplasms (MPLPF; 616871), Lewinsohn et al. (2016) identified a germline heterozygous c.3G-A transition (c.3G-A, NM_016222.2) in the DDX41 gene, resulting in a met1-to-ile (M1I) substitution in the initiation codon. The mutation was predicted to result in a loss of function. There was evidence of incomplete penetrance in both families. In 1 family, a carrier of the mutation did not have a hematologic malignancy, but did have a history inflammatory-related disorders, including sarcoidosis and eczema. Analysis of patient cells showed that the mutation resulted in the production of a smaller protein from use of an alternative translation initiation site. The smaller isoform showed reduced nuclear localization, consistent with the loss of a predicted nuclear localization signal. </p>
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</span>
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</div>
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<div>
|
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0006 MYELOPROLIFERATIVE/LYMPHOPROLIFERATIVE NEOPLASMS, FAMILIAL (MULTIPLE TYPES), SUSCEPTIBILITY TO</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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DDX41, ARG164TRP
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<br />
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SNP: rs142143752,
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gnomAD: rs142143752,
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ClinVar: RCV000210264, RCV001818508, RCV004975332
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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 members of a family (CCB 25476) of Dutch-Sri Lankan descent with familial myeloproliferative/lymphoproliferative neoplasms (MPLPF; 616871), Lewinsohn et al. (2016) identified a germline heterozygous c.490C-T transition (c.490C-T, NM_016222.2) in the DDX41 gene, resulting in an arg164-to-trp (R164W) substitution at a highly conserved residue adjacent to the Q motif. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the 1000 Genomes Project database; it was found at a very low frequency (0.014%) in the ExAC database. There was evidence of incomplete penetrance. The 4 patients with a confirmed mutation had lymphoma, and there was a family history of multiple myeloma in previous generations. Several variant-carrying family members had inflammatory-mediated disorders without overt hematologic malignancies. Functional studies of the variant were not performed, but it was predicted to affect DDX41 helicase activity. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
|
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<p class="mim-text-font">
|
|
Gross, M. B.
|
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<strong>Personal Communication.</strong>
|
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Baltimore, Md. 3/23/2016.
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Irion, U., Leptin, M.
|
|
<strong>Developmental and cell biological functions of the Drosophila DEAD-box protein Abstrakt.</strong>
|
|
Curr. Biol. 9: 1373-1381, 1999.
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[PubMed: 10607561]
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[Full Text: https://doi.org/10.1016/s0960-9822(00)80082-2]
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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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Lewinsohn, M., Brown, A. L., Weinel, L. M., Phung, C., Rafidi, G., Lee, M. K., Schreiber, A. W., Feng, J., Babic, M., Chong, C.-E., Lee, Y., Yong, A., and 18 others.
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<strong>Novel germ line DDX41 mutations define families with a lower age of MDS/AML onset and lymphoid malignancies.</strong>
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Blood 127: 1017-1023, 2016.
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[PubMed: 26712909]
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[Full Text: https://doi.org/10.1182/blood-2015-10-676098]
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Polprasert, C., Schulze, I., Sekeres, M. A., Makishima, H., Przychodzen, B., Hosono, N., Singh, J., Padgett, R. A., Gu, X., Phillips, J. G., Clemente, M., Parker, Y., and 24 others.
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<strong>Inherited and somatic defects in DDX41 in myeloid neoplasms.</strong>
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Cancer Cell 27: 658-670, 2015.
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[PubMed: 25920683]
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[Full Text: https://doi.org/10.1016/j.ccell.2015.03.017]
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Matthew B. Gross - updated : 03/23/2016<br>Cassandra L. Kniffin - updated : 3/22/2016
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Patricia A. Hartz : 10/14/2003
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alopez : 03/16/2023<br>mgross : 07/14/2020<br>carol : 10/04/2016<br>mgross : 03/23/2016<br>carol : 3/22/2016<br>ckniffin : 3/22/2016<br>mgross : 10/14/2003
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