3479 lines
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Entry
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- *608897 - UNC13 HOMOLOG D; UNC13D
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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">*608897</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<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/608897">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div class="panel 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=ENSG00000092929;t=ENST00000207549" 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=201294" 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=608897" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000092929;t=ENST00000207549" 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_199242" 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_199242" 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=608897" 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=10598&isoform_id=10598_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/UNC13D" 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/10440462,40252318,45501049,46195765,51316668,119609728,119609729,119609730,194376940,194390618" 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/Q70J99" 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=201294" 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=ENSG00000092929;t=ENST00000207549" 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=UNC13D" 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=UNC13D" 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+201294" 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/UNC13D" 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:201294" 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/201294" 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=chr17&hgg_gene=ENST00000207549.9&hgg_start=75827225&hgg_end=75844404&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:23147" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/unc13d" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=608897[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 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=608897[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/UNC13D/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/ENSG00000092929" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=UNC13D" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=UNC13D" 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=UNC13D" 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="#mimLocusSpecificDBsFold" id="mimLocusSpecificDBsToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A gene-specific database of variation."><span id="mimLocusSpecificDBsToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Locus Specific DBs</div>
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<div id="mimLocusSpecificDBsFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="http://structure.bmc.lu.se/idbase/UNC13Dbase/" title="UNC13Dbase: Mutation registry for Familial hemophagocytic lymphohistiocytosis 3" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">UNC13Dbase: Mutation regis…</a></div><div style="margin-left: 0.5em;"><a href="http://www.LOVD.nl/UNC13D" title="CCHMC - Human Genetics Mutation Database" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">CCHMC - Human Genetics Mut…</a></div>
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</div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=UNC13D&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/PA134919958" 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:23147" 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/FBgn0035756.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:1917700" 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/UNC13D#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:1917700" 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/201294/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=201294" 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=WBGene00018837;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-110411-188" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://reactome.org/content/query?q=UNC13D&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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608897
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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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UNC13 HOMOLOG D; UNC13D
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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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UNC13, C. ELEGANS, HOMOLOG OF, D<br />
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MUNC13-4
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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=UNC13D" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">UNC13D</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/17/954?start=-3&limit=10&highlight=954">17q25.1</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr17:75827225-75844404&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'})">17:75,827,225-75,844,404</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/17/954?start=-3&limit=10&highlight=954">
|
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17q25.1
|
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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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Hemophagocytic lymphohistiocytosis, familial, 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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<a href="/entry/608898"> 608898 </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 recessive">AR</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
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PheneGene Graphics <span class="caret"></span>
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
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<li><a href="/graph/linear/608897" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/608897" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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</ul>
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</div>
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<p>By coimmunopurification of GTP-RAB27A (<a href="/entry/603868">603868</a>)-interacting proteins in platelets, followed by sequence analysis, database analysis, and PCR of a bone marrow cDNA library, <a href="#7" class="mim-tip-reference" title="Shirakawa, R., Higashi, T., Tabuchi, A., Yoshioka, A., Nishioka, H., Fukuda, M., Kita, T., Horiuch, H. <strong>Munc13-4 is a GTP-Rab27-binding protein regulating dense core granule secretion in platelets.</strong> J. Biol. Chem. 279: 10730-10737, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14699162/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14699162</a>] [<a href="https://doi.org/10.1074/jbc.M309426200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14699162">Shirakawa et al. (2004)</a> cloned full-length UNC13D, which they called MUNC13-4. The deduced 1,090-amino acid protein contains 2 calcium-binding C2 domains and 2 Munc13 homology domains, but it lacks the N-terminal region containing a phorbol ester-binding C1 domain present in other Munc13 proteins, such as UNC13B (<a href="/entry/605836">605836</a>). MUNC13-4 distributed between the cytosol and membrane fractions in permeabilized platelets. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14699162" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using Northern blot analysis, <a href="#2" class="mim-tip-reference" title="Feldmann, J., Callebaut, I., Raposo, G., Certain, S., Bacq, D., Dumont, C., Lambert, N., Ouachee-Chardin, M., Chedeville, G., Tamary, H., Minard-Colin, V., Vilmer, E., Blanche, S., Le Deist, F., Fischer, A., de Saint Basile, G. <strong>Munc13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3).</strong> Cell 115: 461-473, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14622600/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14622600</a>] [<a href="https://doi.org/10.1016/s0092-8674(03)00855-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14622600">Feldmann et al. (2003)</a> detected a 4.5-kb UNC13D transcript that was highly expressed in spleen, thymus, and peripheral blood leukocytes. Faint expression was detected in small intestine, prostate, ovary, and colon. RT-PCR analysis showed high expression of UNC13D in all hematopoietic tissues and cells examined. In nonhematopoietic tissues, strong expression of UNC13D was detected only in lung and placenta, with weak expression in brain, heart, skeletal muscle, and kidney. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14622600" 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>Secretion of the contents of cytolytic granules at the immunologic synapse is a highly regulated process essential for lymphocyte cytotoxicity. This process requires the rapid transfer of perforin (<a href="/entry/170280">170280</a>)-containing lytic granules to the target cell interface, followed by their docking and fusion with the plasma membrane. <a href="#2" class="mim-tip-reference" title="Feldmann, J., Callebaut, I., Raposo, G., Certain, S., Bacq, D., Dumont, C., Lambert, N., Ouachee-Chardin, M., Chedeville, G., Tamary, H., Minard-Colin, V., Vilmer, E., Blanche, S., Le Deist, F., Fischer, A., de Saint Basile, G. <strong>Munc13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3).</strong> Cell 115: 461-473, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14622600/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14622600</a>] [<a href="https://doi.org/10.1016/s0092-8674(03)00855-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14622600">Feldmann et al. (2003)</a> found that expressed tagged UNC13D localized with cytotoxic granules at the immunologic synapse. Using UNC13D-deficient cells, they determined that UNC13D is essential for the priming step of cytolytic granule secretion preceding vesicle membrane fusion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14622600" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Shirakawa, R., Higashi, T., Tabuchi, A., Yoshioka, A., Nishioka, H., Fukuda, M., Kita, T., Horiuch, H. <strong>Munc13-4 is a GTP-Rab27-binding protein regulating dense core granule secretion in platelets.</strong> J. Biol. Chem. 279: 10730-10737, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14699162/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14699162</a>] [<a href="https://doi.org/10.1074/jbc.M309426200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14699162">Shirakawa et al. (2004)</a> found that MUNC13-4 bound GTP-RAB27A and GTP-RAB27B (<a href="/entry/603869">603869</a>) in vitro, but not other GTPases, and it enhanced platelet secretion in an in vitro assay. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14699162" 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="Feldmann, J., Callebaut, I., Raposo, G., Certain, S., Bacq, D., Dumont, C., Lambert, N., Ouachee-Chardin, M., Chedeville, G., Tamary, H., Minard-Colin, V., Vilmer, E., Blanche, S., Le Deist, F., Fischer, A., de Saint Basile, G. <strong>Munc13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3).</strong> Cell 115: 461-473, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14622600/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14622600</a>] [<a href="https://doi.org/10.1016/s0092-8674(03)00855-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14622600">Feldmann et al. (2003)</a> determined that the UNC13D gene contains 32 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14622600" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By genomic sequence analysis, <a href="#2" class="mim-tip-reference" title="Feldmann, J., Callebaut, I., Raposo, G., Certain, S., Bacq, D., Dumont, C., Lambert, N., Ouachee-Chardin, M., Chedeville, G., Tamary, H., Minard-Colin, V., Vilmer, E., Blanche, S., Le Deist, F., Fischer, A., de Saint Basile, G. <strong>Munc13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3).</strong> Cell 115: 461-473, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14622600/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14622600</a>] [<a href="https://doi.org/10.1016/s0092-8674(03)00855-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14622600">Feldmann et al. (2003)</a> mapped the UNC13D gene to chromosome 17q25.1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14622600" 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="Feldmann, J., Callebaut, I., Raposo, G., Certain, S., Bacq, D., Dumont, C., Lambert, N., Ouachee-Chardin, M., Chedeville, G., Tamary, H., Minard-Colin, V., Vilmer, E., Blanche, S., Le Deist, F., Fischer, A., de Saint Basile, G. <strong>Munc13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3).</strong> Cell 115: 461-473, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14622600/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14622600</a>] [<a href="https://doi.org/10.1016/s0092-8674(03)00855-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14622600">Feldmann et al. (2003)</a> identified 6 mutations in the UNC13D gene in patients with hemophagocytic lymphohistiocytosis-3 (FHL3; <a href="/entry/608898">608898</a>). They found that UNC13D deficiency resulted in defective cytolytic granule exocytosis, despite polarization of the secretory granules and docking with the plasma membrane. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14622600" 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>Noting that mutations in the perforin gene (PRF1; <a href="/entry/170280">170280</a>) account for only about 40% of cases of hemophagocytic lymphohistiocytosis, <a href="#6" class="mim-tip-reference" title="Santoro, A., Cannella, S., Bossi, G., Gallo, F., Trizzino, A., Pende, D., Dieli, F., Bruno, G., Stinchcombe, J. C., Micalizzi, C., De Fusco, C., Danesino, C., Moretta, L., Notarangelo, L. D., Griffiths, G. M., Arico, M. <strong>Novel Munc13-4 mutations in children and young adult patients with haemophagocytic lymphohistiocytosis. (Letter)</strong> J. Med. Genet. 43: 953-960, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16825436/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16825436</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16825436[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/10.1136/jmg.2006.041863" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16825436">Santoro et al. (2006)</a> sequenced the UNC13D gene in 30 probands with hemophagocytic lymphohistiocytosis who did not have mutations in PRF1. In 15 families, 12 novel and 4 known mutations were found, spread throughout the gene (see, e.g., <a href="#0001">608897.0001</a>, <a href="#0006">608897.0006</a>, and <a href="#0009">608897.0009</a>). The mutations were homozygous in 8 families and compound heterozygous in 7. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16825436" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Variant Studies</em></strong></p><p>
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<a href="#4" class="mim-tip-reference" title="Noori, T., Rudd-Schmidt, J. A., Kane, A., Frith, K., Gray, P. E., Hu, H., Hsu, D., Chung, C. W. T., Hodel, A. W., Trapani, J. A., Voskoboinik, I. <strong>A cell-based functional assay that accurately links genotype to phenotype in familial HLH.</strong> Blood 141: 2330-2342, 2023. Note: Erratum: Blood 143: 562 only, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36706356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36706356</a>] [<a href="https://doi.org/10.1182/blood.2022018398" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="36706356">Noori et al. (2023)</a> developed an in vitro assay to determine the clinical relevance of mutations in the UNC13D, STXBP2 (<a href="/entry/601717">601717</a>), PRF1 (<a href="/entry/170280">170280</a>), and STX11 (<a href="/entry/605014">605014</a>) genes identified in patients with HLH, with the goal of distinguishing patients with familial hemophagocytic lymphohistiocytosis from patients with nonfamilial hemophagocytic lymphohistiocytosis. In this assay, the mouse homolog of the relevant mutated gene was removed by Cas9 ribonucleoprotein in naive murine CD8+ T cells, and then the cells were transduced with cDNA of the human homolog containing the patient's mutation to be studied. The cells were then tested for cytotoxicity and degranulation capacity. <a href="#4" class="mim-tip-reference" title="Noori, T., Rudd-Schmidt, J. A., Kane, A., Frith, K., Gray, P. E., Hu, H., Hsu, D., Chung, C. W. T., Hodel, A. W., Trapani, J. A., Voskoboinik, I. <strong>A cell-based functional assay that accurately links genotype to phenotype in familial HLH.</strong> Blood 141: 2330-2342, 2023. Note: Erratum: Blood 143: 562 only, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36706356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36706356</a>] [<a href="https://doi.org/10.1182/blood.2022018398" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="36706356">Noori et al. (2023)</a> tested mutations previously identified in patients with HLH and found that biallelic mutations resulting in complete loss of function were identified in infants or very young children with HLH, whereas partial loss of function mutations in one or more alleles were identified in older children or adults with HLH. Interestingly, the authors found that the level of protein expression resulting from a gene mutation did not necessarily correlate to the level of residual function. <a href="#3" class="mim-tip-reference" title="Meyer, L. K., Nichols, K. E. <strong>Deciphering genetic uncertainty in familial HLH.</strong> Blood 141: 2288-2290, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/37166930/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">37166930</a>] [<a href="https://doi.org/10.1182/blood.2023019713" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="37166930">Meyer and Nichols (2023)</a> commented that this assay may not appropriately characterize dominant-negative mutations or biallelic mutations with complementary effects. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=36706356+37166930" 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="Crozat, K., Hoebe, K., Ugolini, S., Hong, N. A., Janssen, E., Rutschmann, S., Mudd, S., Sovath, S., Vivier, E., Beutler, B. <strong>Jinx, an MCMV susceptibility phenotype caused by disruption of Unc13d: a mouse model of type 3 familial hemophagocytic lymphohistiocytosis.</strong> J. Exp. Med. 204: 853-863, 2007. Note: Erratum: J. Exp. Med. 205: 737 only, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17420270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17420270</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17420270[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/10.1084/jem.20062447" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17420270">Crozat et al. (2007)</a> described Jinx, an N-ethyl-N-nitrosourea-induced murine cytomegalovirus (MCMV) susceptibility mutation in C57BL/6 mice. They identified the Jinx mutation as an insertion of 53 nucleotides from intron 26 into exon 26 of the Unc13d gene, resulting in a 20-amino acid insertion, followed by premature termination after amino acid 859. In addition to increased MCMV viral titers and lethality comparable to that observed in susceptible BALB/c mice, Jinx mice produced high levels of Ifng (<a href="/entry/147570">147570</a>) and Ifna (<a href="/entry/147660">147660</a>)/Ifnb (<a href="/entry/147640">147640</a>) after infection, but they were unable to kill natural killer (NK) target cells. Both NK and cytotoxic T lymphocytes failed to degranulate in Jinx mice. Jinx mice showed no increased susceptibility to Listeria monocytogenes. Jinx mice developed an FHL3-like phenotype after infection with lymphocytic choriomeningitis virus (LCMV), but not after infection with MCMV. One exception to the FHL3-like phenotype was that instead of neutropenia, Jinx mice developed neutrophilia after infection with LCMV. <a href="#1" class="mim-tip-reference" title="Crozat, K., Hoebe, K., Ugolini, S., Hong, N. A., Janssen, E., Rutschmann, S., Mudd, S., Sovath, S., Vivier, E., Beutler, B. <strong>Jinx, an MCMV susceptibility phenotype caused by disruption of Unc13d: a mouse model of type 3 familial hemophagocytic lymphohistiocytosis.</strong> J. Exp. Med. 204: 853-863, 2007. Note: Erratum: J. Exp. Med. 205: 737 only, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17420270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17420270</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17420270[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/10.1084/jem.20062447" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17420270">Crozat et al. (2007)</a> concluded that development of hemophagocytic lymphohistiocytosis in mice is conditional and proposed that there may also be a specific infectious trigger of FHL3 in humans. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17420270" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using Jinx mice to analyze platelet granule release and secretion, <a href="#5" class="mim-tip-reference" title="Ren, Q., Wimmer, C., Chicka, M. C., Ye, S., Ren, Y., Hughson, F. M., Whiteheart, S. W. <strong>Munc13-4 is a limiting factor in the pathway required for platelet granule release and hemostasis.</strong> Blood 116: 869-877, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20435885/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20435885</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20435885[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1182/blood-2010-02-270934" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20435885">Ren et al. (2010)</a> observed complete ablation of release from dense granules and compromised activity from alpha granules and lysosomes. Platelets from Jinx mice showed attenuated aggregation, and Jinx mice had prolonged bleeding times. Defective release was rescued by addition of recombinant human UNC13D to permeabilized Jinx platelets. Unc13d levels correlated directly with the extent of granule release from wildtype and Jinx heterozygous mouse platelets. <a href="#5" class="mim-tip-reference" title="Ren, Q., Wimmer, C., Chicka, M. C., Ye, S., Ren, Y., Hughson, F. M., Whiteheart, S. W. <strong>Munc13-4 is a limiting factor in the pathway required for platelet granule release and hemostasis.</strong> Blood 116: 869-877, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20435885/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20435885</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20435885[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1182/blood-2010-02-270934" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20435885">Ren et al. (2010)</a> concluded that UNC13D is a limiting factor required for platelet secretion and hemostasis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20435885" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>9 Selected Examples</a>):</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=608897[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<strong>.0001 HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL, 3</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">rs796065024 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs796065024;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=rs796065024" 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=rs796065024" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In patients with familial hemophagocytic lymphohistiocytosis-3 (FHL3; <a href="/entry/608898">608898</a>) from 3 Moroccan families, <a href="#2" class="mim-tip-reference" title="Feldmann, J., Callebaut, I., Raposo, G., Certain, S., Bacq, D., Dumont, C., Lambert, N., Ouachee-Chardin, M., Chedeville, G., Tamary, H., Minard-Colin, V., Vilmer, E., Blanche, S., Le Deist, F., Fischer, A., de Saint Basile, G. <strong>Munc13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3).</strong> Cell 115: 461-473, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14622600/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14622600</a>] [<a href="https://doi.org/10.1016/s0092-8674(03)00855-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14622600">Feldmann et al. (2003)</a> identified homozygosity for a 12-bp deletion at nucleotide 1822 within exon 20 of the UNC13D gene. The mutation resulted in the deletion of amino acids 608 to 611. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14622600" 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 a Moroccan patient with FHL, <a href="#6" class="mim-tip-reference" title="Santoro, A., Cannella, S., Bossi, G., Gallo, F., Trizzino, A., Pende, D., Dieli, F., Bruno, G., Stinchcombe, J. C., Micalizzi, C., De Fusco, C., Danesino, C., Moretta, L., Notarangelo, L. D., Griffiths, G. M., Arico, M. <strong>Novel Munc13-4 mutations in children and young adult patients with haemophagocytic lymphohistiocytosis. (Letter)</strong> J. Med. Genet. 43: 953-960, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16825436/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16825436</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16825436[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/10.1136/jmg.2006.041863" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16825436">Santoro et al. (2006)</a> identified homozygosity for the 1822del12 mutation in the UNC13D gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16825436" 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 patients with familial hemophagocytic lymphohistiocytosis-3 (FHL3; <a href="/entry/608898">608898</a>) from a Pakistani family, <a href="#2" class="mim-tip-reference" title="Feldmann, J., Callebaut, I., Raposo, G., Certain, S., Bacq, D., Dumont, C., Lambert, N., Ouachee-Chardin, M., Chedeville, G., Tamary, H., Minard-Colin, V., Vilmer, E., Blanche, S., Le Deist, F., Fischer, A., de Saint Basile, G. <strong>Munc13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3).</strong> Cell 115: 461-473, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14622600/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14622600</a>] [<a href="https://doi.org/10.1016/s0092-8674(03)00855-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14622600">Feldmann et al. (2003)</a> identified homozygosity for a deletion of nucleotide 214C in exon 3 of the UNC13D gene, resulting in a frameshift after codon 72. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14622600" 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 HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL, 3</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">rs796065026 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs796065026;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=rs796065026" 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=rs796065026" 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=RCV000002075" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002075" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002075</a>
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<p>In an Arabian patient with familial hemophagocytic lymphohistiocytosis-3 (FHL3; <a href="/entry/608898">608898</a>), <a href="#2" class="mim-tip-reference" title="Feldmann, J., Callebaut, I., Raposo, G., Certain, S., Bacq, D., Dumont, C., Lambert, N., Ouachee-Chardin, M., Chedeville, G., Tamary, H., Minard-Colin, V., Vilmer, E., Blanche, S., Le Deist, F., Fischer, A., de Saint Basile, G. <strong>Munc13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3).</strong> Cell 115: 461-473, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14622600/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14622600</a>] [<a href="https://doi.org/10.1016/s0092-8674(03)00855-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14622600">Feldmann et al. (2003)</a> identified homozygosity for an insertion of T at nucleotide 1755 in exon 20 of the UNC13D gene, resulting in a frameshift after codon 586. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14622600" 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> rs777759523 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs777759523;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/rs777759523?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=rs777759523" 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=rs777759523" 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=RCV000002076 OR RCV000380656 OR RCV002262537" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002076, RCV000380656, RCV002262537" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002076...</a>
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<p>In a French patient with familial hemophagocytic lymphohistiocytosis-3 (FHL3; <a href="/entry/608898">608898</a>), <a href="#2" class="mim-tip-reference" title="Feldmann, J., Callebaut, I., Raposo, G., Certain, S., Bacq, D., Dumont, C., Lambert, N., Ouachee-Chardin, M., Chedeville, G., Tamary, H., Minard-Colin, V., Vilmer, E., Blanche, S., Le Deist, F., Fischer, A., de Saint Basile, G. <strong>Munc13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3).</strong> Cell 115: 461-473, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14622600/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14622600</a>] [<a href="https://doi.org/10.1016/s0092-8674(03)00855-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14622600">Feldmann et al. (2003)</a> identified homozygosity for a G-to-A transition at the donor splice site of intron 15 of the UNC13D gene, resulting in abnormal splicing and frameshift after codon 464. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14622600" 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 HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL, 3</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> rs121434352 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434352;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/rs121434352?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=rs121434352" 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=rs121434352" 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=RCV000002077 OR RCV000760447 OR RCV002262538 OR RCV004745140" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002077, RCV000760447, RCV002262538, RCV004745140" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002077...</a>
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<p>In patients with familial hemophagocytic lymphohistiocytosis-3 (FHL3; <a href="/entry/608898">608898</a>) from a French family, <a href="#2" class="mim-tip-reference" title="Feldmann, J., Callebaut, I., Raposo, G., Certain, S., Bacq, D., Dumont, C., Lambert, N., Ouachee-Chardin, M., Chedeville, G., Tamary, H., Minard-Colin, V., Vilmer, E., Blanche, S., Le Deist, F., Fischer, A., de Saint Basile, G. <strong>Munc13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3).</strong> Cell 115: 461-473, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14622600/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14622600</a>] [<a href="https://doi.org/10.1016/s0092-8674(03)00855-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14622600">Feldmann et al. (2003)</a> identified compound heterozygosity for a C-to-T transition at nucleotide 766 in exon 10 of the UNC13D gene, resulting in an arg256-to-ter (R256X) substitution, and a G-to-T transversion at the donor splice site of intron 9 (<a href="#0006">608897.0006</a>), resulting in abnormal splicing and frameshift after codon 252. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14622600" 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 HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL, 3</strong>
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UNC13D, IVS9DS, G-T, +1
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000002078 OR RCV000288588" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002078, RCV000288588" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002078...</a>
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<p>For discussion of the G-to-T transversion at the donor splice site of intron 9 in the UNC13D gene that was found in compound heterozygous state in patients with familial hemophagocytic lymphohistiocytosis-3 (FHL3; <a href="/entry/608898">608898</a>) by <a href="#2" class="mim-tip-reference" title="Feldmann, J., Callebaut, I., Raposo, G., Certain, S., Bacq, D., Dumont, C., Lambert, N., Ouachee-Chardin, M., Chedeville, G., Tamary, H., Minard-Colin, V., Vilmer, E., Blanche, S., Le Deist, F., Fischer, A., de Saint Basile, G. <strong>Munc13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3).</strong> Cell 115: 461-473, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14622600/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14622600</a>] [<a href="https://doi.org/10.1016/s0092-8674(03)00855-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14622600">Feldmann et al. (2003)</a>, see <a href="#0005">608897.0005</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14622600" 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 3 unrelated Italian patients with FHL, <a href="#6" class="mim-tip-reference" title="Santoro, A., Cannella, S., Bossi, G., Gallo, F., Trizzino, A., Pende, D., Dieli, F., Bruno, G., Stinchcombe, J. C., Micalizzi, C., De Fusco, C., Danesino, C., Moretta, L., Notarangelo, L. D., Griffiths, G. M., Arico, M. <strong>Novel Munc13-4 mutations in children and young adult patients with haemophagocytic lymphohistiocytosis. (Letter)</strong> J. Med. Genet. 43: 953-960, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16825436/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16825436</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16825436[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/10.1136/jmg.2006.041863" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16825436">Santoro et al. (2006)</a> identified compound heterozygosity for the +1G-T transversion in intron 9 of the UNC13D gene and another mutation in UNC13D (see, e.g., <a href="#0009">608897.0009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16825436" 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>.0007 HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL, 3</strong>
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UNC13D, LEU403PRO
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121434353 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434353;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=rs121434353" 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=rs121434353" 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=RCV000002079" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002079" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002079</a>
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<p>In a Turkish patient who had primary hemophagocytic lymphohistiocytosis (FHL3; <a href="/entry/608898">608898</a>), <a href="#8" class="mim-tip-reference" title="Zur Stadt, U., Beutel, K., Kolberg, S., Schneppenheim, R., Kabisch, H., Janka, G., Hennies, H. C. <strong>Mutation spectrum in children with primary hemophagocytic lymphohistiocytosis: molecular and functional analyses of PRF1, UNC13D, STX11, and RAB27A.</strong> Hum. Mutat. 27: 62-68, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16278825/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16278825</a>] [<a href="https://doi.org/10.1002/humu.20274" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16278825">Zur Stadt et al. (2006)</a> found homozygosity for a leu403-to-pro (L403P) mutation in the UNC13D gene. The family was consanguineous, and the diagnosis in the patient had been made at the age of 2 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16278825" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0008 MOVED TO <a href="/entry/608897#0006">608897.0006</a></strong>
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<strong>.0009 HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL, 3</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">rs121434354 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434354;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=rs121434354" 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=rs121434354" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In an Italian family with primary hemophagocytic lymphohistiocytosis (FHL3; <a href="/entry/608898">608898</a>), <a href="#6" class="mim-tip-reference" title="Santoro, A., Cannella, S., Bossi, G., Gallo, F., Trizzino, A., Pende, D., Dieli, F., Bruno, G., Stinchcombe, J. C., Micalizzi, C., De Fusco, C., Danesino, C., Moretta, L., Notarangelo, L. D., Griffiths, G. M., Arico, M. <strong>Novel Munc13-4 mutations in children and young adult patients with haemophagocytic lymphohistiocytosis. (Letter)</strong> J. Med. Genet. 43: 953-960, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16825436/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16825436</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16825436[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/10.1136/jmg.2006.041863" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16825436">Santoro et al. (2006)</a> identified compound heterozygosity for mutations in the UNC13D gene: a 2570T-G transversion in exon 27, resulting in a phe857-to-cys (F857C) substitution, and a splice site mutation (<a href="#0006">608897.0006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16825436" 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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<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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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 id="mimReferencesFold" class="collapse in mimTextToggleFold">
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<ol>
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<a id="1" class="mim-anchor"></a>
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<a id="Crozat2007" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Crozat, K., Hoebe, K., Ugolini, S., Hong, N. A., Janssen, E., Rutschmann, S., Mudd, S., Sovath, S., Vivier, E., Beutler, B.
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|
<strong>Jinx, an MCMV susceptibility phenotype caused by disruption of Unc13d: a mouse model of type 3 familial hemophagocytic lymphohistiocytosis.</strong>
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|
J. Exp. Med. 204: 853-863, 2007. Note: Erratum: J. Exp. Med. 205: 737 only, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17420270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17420270</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17420270[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=17420270" 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/10.1084/jem.20062447" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="2" class="mim-anchor"></a>
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<a id="Feldmann2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Feldmann, J., Callebaut, I., Raposo, G., Certain, S., Bacq, D., Dumont, C., Lambert, N., Ouachee-Chardin, M., Chedeville, G., Tamary, H., Minard-Colin, V., Vilmer, E., Blanche, S., Le Deist, F., Fischer, A., de Saint Basile, G.
|
|
<strong>Munc13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3).</strong>
|
|
Cell 115: 461-473, 2003.
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|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14622600/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14622600</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14622600" 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/s0092-8674(03)00855-9" target="_blank">Full Text</a>]
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</p>
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<a id="3" class="mim-anchor"></a>
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<a id="Meyer2023" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Meyer, L. K., Nichols, K. E.
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<strong>Deciphering genetic uncertainty in familial HLH.</strong>
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|
Blood 141: 2288-2290, 2023.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/37166930/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">37166930</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=37166930" 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.2023019713" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="4" class="mim-anchor"></a>
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<a id="Noori2023" class="mim-anchor"></a>
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<div class="mim-changed mim-change">
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<p class="mim-text-font">
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Noori, T., Rudd-Schmidt, J. A., Kane, A., Frith, K., Gray, P. E., Hu, H., Hsu, D., Chung, C. W. T., Hodel, A. W., Trapani, J. A., Voskoboinik, I.
|
|
<strong>A cell-based functional assay that accurately links genotype to phenotype in familial HLH.</strong>
|
|
Blood 141: 2330-2342, 2023. Note: Erratum: Blood 143: 562 only, 2024.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36706356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36706356</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36706356" 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.2022018398" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="5" class="mim-anchor"></a>
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<a id="Ren2010" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Ren, Q., Wimmer, C., Chicka, M. C., Ye, S., Ren, Y., Hughson, F. M., Whiteheart, S. W.
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<strong>Munc13-4 is a limiting factor in the pathway required for platelet granule release and hemostasis.</strong>
|
|
Blood 116: 869-877, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20435885/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20435885</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20435885[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=20435885" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1182/blood-2010-02-270934" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="6" class="mim-anchor"></a>
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<a id="Santoro2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Santoro, A., Cannella, S., Bossi, G., Gallo, F., Trizzino, A., Pende, D., Dieli, F., Bruno, G., Stinchcombe, J. C., Micalizzi, C., De Fusco, C., Danesino, C., Moretta, L., Notarangelo, L. D., Griffiths, G. M., Arico, M.
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|
<strong>Novel Munc13-4 mutations in children and young adult patients with haemophagocytic lymphohistiocytosis. (Letter)</strong>
|
|
J. Med. Genet. 43: 953-960, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16825436/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16825436</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16825436[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=16825436" 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/10.1136/jmg.2006.041863" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="7" class="mim-anchor"></a>
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<a id="Shirakawa2004" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Shirakawa, R., Higashi, T., Tabuchi, A., Yoshioka, A., Nishioka, H., Fukuda, M., Kita, T., Horiuch, H.
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<strong>Munc13-4 is a GTP-Rab27-binding protein regulating dense core granule secretion in platelets.</strong>
|
|
J. Biol. Chem. 279: 10730-10737, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14699162/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14699162</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14699162" 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/10.1074/jbc.M309426200" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="8" class="mim-anchor"></a>
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<a id="Zur Stadt2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zur Stadt, U., Beutel, K., Kolberg, S., Schneppenheim, R., Kabisch, H., Janka, G., Hennies, H. C.
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<strong>Mutation spectrum in children with primary hemophagocytic lymphohistiocytosis: molecular and functional analyses of PRF1, UNC13D, STX11, and RAB27A.</strong>
|
|
Hum. Mutat. 27: 62-68, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16278825/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16278825</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16278825" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/humu.20274" target="_blank">Full Text</a>]
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</p>
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</div>
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</ol>
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<div>
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<br />
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</div>
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<a id="contributors" class="mim-anchor"></a>
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Hilary J. Vernon - updated : 06/04/2024
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</span>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Paul J. Converse - updated : 7/1/2011<br>Marla J. F. O'Neill - updated : 11/12/2008<br>Victor A. McKusick - updated : 5/31/2007<br>Victor A. McKusick - updated : 1/20/2006<br>Patricia A. Hartz - updated : 11/5/2004
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</span>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Stylianos E. Antonarakis : 9/3/2004
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</span>
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</div>
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<a id="editHistory" class="mim-anchor"></a>
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 01/15/2025
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</span>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 06/05/2024<br>carol : 06/04/2024<br>carol : 09/09/2019<br>carol : 07/19/2017<br>carol : 05/23/2017<br>alopez : 09/09/2015<br>mcolton : 8/3/2015<br>mgross : 7/7/2011<br>mgross : 7/7/2011<br>terry : 7/1/2011<br>wwang : 11/13/2008<br>terry : 11/12/2008<br>alopez : 6/5/2007<br>terry : 5/31/2007<br>alopez : 3/8/2006<br>terry : 1/20/2006<br>mgross : 11/10/2004<br>terry : 11/5/2004<br>mgross : 9/3/2004
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</span>
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</div>
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</div>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 608897
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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UNC13 HOMOLOG D; UNC13D
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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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<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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UNC13, C. ELEGANS, HOMOLOG OF, D<br />
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MUNC13-4
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: UNC13D</em></strong>
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 17q25.1
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Genomic coordinates <span class="small">(GRCh38)</span> : 17:75,827,225-75,844,404 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
|
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<div>
|
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
|
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Inheritance
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</th>
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<th>
|
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Phenotype <br /> mapping key
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</th>
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</tr>
|
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</thead>
|
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<tbody>
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<tr>
|
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<td rowspan="1">
|
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<span class="mim-font">
|
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17q25.1
|
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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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Hemophagocytic lymphohistiocytosis, familial, 3
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
608898
|
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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 recessive
|
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</span>
|
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</td>
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<td>
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<span class="mim-font">
|
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3
|
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By coimmunopurification of GTP-RAB27A (603868)-interacting proteins in platelets, followed by sequence analysis, database analysis, and PCR of a bone marrow cDNA library, Shirakawa et al. (2004) cloned full-length UNC13D, which they called MUNC13-4. The deduced 1,090-amino acid protein contains 2 calcium-binding C2 domains and 2 Munc13 homology domains, but it lacks the N-terminal region containing a phorbol ester-binding C1 domain present in other Munc13 proteins, such as UNC13B (605836). MUNC13-4 distributed between the cytosol and membrane fractions in permeabilized platelets. </p><p>Using Northern blot analysis, Feldmann et al. (2003) detected a 4.5-kb UNC13D transcript that was highly expressed in spleen, thymus, and peripheral blood leukocytes. Faint expression was detected in small intestine, prostate, ovary, and colon. RT-PCR analysis showed high expression of UNC13D in all hematopoietic tissues and cells examined. In nonhematopoietic tissues, strong expression of UNC13D was detected only in lung and placenta, with weak expression in brain, heart, skeletal muscle, and kidney. </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>Secretion of the contents of cytolytic granules at the immunologic synapse is a highly regulated process essential for lymphocyte cytotoxicity. This process requires the rapid transfer of perforin (170280)-containing lytic granules to the target cell interface, followed by their docking and fusion with the plasma membrane. Feldmann et al. (2003) found that expressed tagged UNC13D localized with cytotoxic granules at the immunologic synapse. Using UNC13D-deficient cells, they determined that UNC13D is essential for the priming step of cytolytic granule secretion preceding vesicle membrane fusion. </p><p>Shirakawa et al. (2004) found that MUNC13-4 bound GTP-RAB27A and GTP-RAB27B (603869) in vitro, but not other GTPases, and it enhanced platelet secretion in an in vitro assay. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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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>Feldmann et al. (2003) determined that the UNC13D gene contains 32 exons. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By genomic sequence analysis, Feldmann et al. (2003) mapped the UNC13D gene to chromosome 17q25.1. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>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>Feldmann et al. (2003) identified 6 mutations in the UNC13D gene in patients with hemophagocytic lymphohistiocytosis-3 (FHL3; 608898). They found that UNC13D deficiency resulted in defective cytolytic granule exocytosis, despite polarization of the secretory granules and docking with the plasma membrane. </p><p>Noting that mutations in the perforin gene (PRF1; 170280) account for only about 40% of cases of hemophagocytic lymphohistiocytosis, Santoro et al. (2006) sequenced the UNC13D gene in 30 probands with hemophagocytic lymphohistiocytosis who did not have mutations in PRF1. In 15 families, 12 novel and 4 known mutations were found, spread throughout the gene (see, e.g., 608897.0001, 608897.0006, and 608897.0009). The mutations were homozygous in 8 families and compound heterozygous in 7. </p><p><strong><em>Variant Studies</em></strong></p><p>
|
|
Noori et al. (2023) developed an in vitro assay to determine the clinical relevance of mutations in the UNC13D, STXBP2 (601717), PRF1 (170280), and STX11 (605014) genes identified in patients with HLH, with the goal of distinguishing patients with familial hemophagocytic lymphohistiocytosis from patients with nonfamilial hemophagocytic lymphohistiocytosis. In this assay, the mouse homolog of the relevant mutated gene was removed by Cas9 ribonucleoprotein in naive murine CD8+ T cells, and then the cells were transduced with cDNA of the human homolog containing the patient's mutation to be studied. The cells were then tested for cytotoxicity and degranulation capacity. Noori et al. (2023) tested mutations previously identified in patients with HLH and found that biallelic mutations resulting in complete loss of function were identified in infants or very young children with HLH, whereas partial loss of function mutations in one or more alleles were identified in older children or adults with HLH. Interestingly, the authors found that the level of protein expression resulting from a gene mutation did not necessarily correlate to the level of residual function. Meyer and Nichols (2023) commented that this assay may not appropriately characterize dominant-negative mutations or biallelic mutations with complementary effects. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>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">
|
|
<p>Crozat et al. (2007) described Jinx, an N-ethyl-N-nitrosourea-induced murine cytomegalovirus (MCMV) susceptibility mutation in C57BL/6 mice. They identified the Jinx mutation as an insertion of 53 nucleotides from intron 26 into exon 26 of the Unc13d gene, resulting in a 20-amino acid insertion, followed by premature termination after amino acid 859. In addition to increased MCMV viral titers and lethality comparable to that observed in susceptible BALB/c mice, Jinx mice produced high levels of Ifng (147570) and Ifna (147660)/Ifnb (147640) after infection, but they were unable to kill natural killer (NK) target cells. Both NK and cytotoxic T lymphocytes failed to degranulate in Jinx mice. Jinx mice showed no increased susceptibility to Listeria monocytogenes. Jinx mice developed an FHL3-like phenotype after infection with lymphocytic choriomeningitis virus (LCMV), but not after infection with MCMV. One exception to the FHL3-like phenotype was that instead of neutropenia, Jinx mice developed neutrophilia after infection with LCMV. Crozat et al. (2007) concluded that development of hemophagocytic lymphohistiocytosis in mice is conditional and proposed that there may also be a specific infectious trigger of FHL3 in humans. </p><p>Using Jinx mice to analyze platelet granule release and secretion, Ren et al. (2010) observed complete ablation of release from dense granules and compromised activity from alpha granules and lysosomes. Platelets from Jinx mice showed attenuated aggregation, and Jinx mice had prolonged bleeding times. Defective release was rescued by addition of recombinant human UNC13D to permeabilized Jinx platelets. Unc13d levels correlated directly with the extent of granule release from wildtype and Jinx heterozygous mouse platelets. Ren et al. (2010) concluded that UNC13D is a limiting factor required for platelet secretion and hemostasis. </p>
|
|
</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>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>9 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
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|
<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL, 3</strong>
|
|
</span>
|
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</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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|
|
UNC13D, 12-BP DEL, NT1822
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<br />
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|
|
SNP: rs796065024,
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|
|
|
|
ClinVar: RCV000002073
|
|
|
|
|
|
</span>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In patients with familial hemophagocytic lymphohistiocytosis-3 (FHL3; 608898) from 3 Moroccan families, Feldmann et al. (2003) identified homozygosity for a 12-bp deletion at nucleotide 1822 within exon 20 of the UNC13D gene. The mutation resulted in the deletion of amino acids 608 to 611. </p><p>In a Moroccan patient with FHL, Santoro et al. (2006) identified homozygosity for the 1822del12 mutation in the UNC13D gene. </p>
|
|
</span>
|
|
</div>
|
|
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|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL, 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
UNC13D, 1-BP DEL, 214C
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs796065025,
|
|
|
|
|
|
|
|
ClinVar: RCV000002074
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In patients with familial hemophagocytic lymphohistiocytosis-3 (FHL3; 608898) from a Pakistani family, Feldmann et al. (2003) identified homozygosity for a deletion of nucleotide 214C in exon 3 of the UNC13D gene, resulting in a frameshift after codon 72. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL, 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
UNC13D, 1-BP INS, 1755T
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs796065026,
|
|
|
|
|
|
|
|
ClinVar: RCV000002075
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an Arabian patient with familial hemophagocytic lymphohistiocytosis-3 (FHL3; 608898), Feldmann et al. (2003) identified homozygosity for an insertion of T at nucleotide 1755 in exon 20 of the UNC13D gene, resulting in a frameshift after codon 586. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL, 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
UNC13D, IVS15DS, G-A, +1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs777759523,
|
|
|
|
|
|
gnomAD: rs777759523,
|
|
|
|
|
|
ClinVar: RCV000002076, RCV000380656, RCV002262537
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a French patient with familial hemophagocytic lymphohistiocytosis-3 (FHL3; 608898), Feldmann et al. (2003) identified homozygosity for a G-to-A transition at the donor splice site of intron 15 of the UNC13D gene, resulting in abnormal splicing and frameshift after codon 464. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL, 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
UNC13D, ARG256TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121434352,
|
|
|
|
|
|
gnomAD: rs121434352,
|
|
|
|
|
|
ClinVar: RCV000002077, RCV000760447, RCV002262538, RCV004745140
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In patients with familial hemophagocytic lymphohistiocytosis-3 (FHL3; 608898) from a French family, Feldmann et al. (2003) identified compound heterozygosity for a C-to-T transition at nucleotide 766 in exon 10 of the UNC13D gene, resulting in an arg256-to-ter (R256X) substitution, and a G-to-T transversion at the donor splice site of intron 9 (608897.0006), resulting in abnormal splicing and frameshift after codon 252. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL, 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
UNC13D, IVS9DS, G-T, +1
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000002078, RCV000288588
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the G-to-T transversion at the donor splice site of intron 9 in the UNC13D gene that was found in compound heterozygous state in patients with familial hemophagocytic lymphohistiocytosis-3 (FHL3; 608898) by Feldmann et al. (2003), see 608897.0005. </p><p>In 3 unrelated Italian patients with FHL, Santoro et al. (2006) identified compound heterozygosity for the +1G-T transversion in intron 9 of the UNC13D gene and another mutation in UNC13D (see, e.g., 608897.0009). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL, 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
UNC13D, LEU403PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121434353,
|
|
|
|
|
|
|
|
ClinVar: RCV000002079
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Turkish patient who had primary hemophagocytic lymphohistiocytosis (FHL3; 608898), Zur Stadt et al. (2006) found homozygosity for a leu403-to-pro (L403P) mutation in the UNC13D gene. The family was consanguineous, and the diagnosis in the patient had been made at the age of 2 years. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-text-font">
|
|
<strong>.0008 MOVED TO 608897.0006</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL, 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
UNC13D, PHE857CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121434354,
|
|
|
|
|
|
|
|
ClinVar: RCV000002080
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an Italian family with primary hemophagocytic lymphohistiocytosis (FHL3; 608898), Santoro et al. (2006) identified compound heterozygosity for mutations in the UNC13D gene: a 2570T-G transversion in exon 27, resulting in a phe857-to-cys (F857C) substitution, and a splice site mutation (608897.0006). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
</div>
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Crozat, K., Hoebe, K., Ugolini, S., Hong, N. A., Janssen, E., Rutschmann, S., Mudd, S., Sovath, S., Vivier, E., Beutler, B.
|
|
<strong>Jinx, an MCMV susceptibility phenotype caused by disruption of Unc13d: a mouse model of type 3 familial hemophagocytic lymphohistiocytosis.</strong>
|
|
J. Exp. Med. 204: 853-863, 2007. Note: Erratum: J. Exp. Med. 205: 737 only, 2008.
|
|
|
|
|
|
[PubMed: 17420270]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1084/jem.20062447]
|
|
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|
|
|
</p>
|
|
</li>
|
|
|
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<li>
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Feldmann, J., Callebaut, I., Raposo, G., Certain, S., Bacq, D., Dumont, C., Lambert, N., Ouachee-Chardin, M., Chedeville, G., Tamary, H., Minard-Colin, V., Vilmer, E., Blanche, S., Le Deist, F., Fischer, A., de Saint Basile, G.
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<strong>Munc13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3).</strong>
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Cell 115: 461-473, 2003.
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[PubMed: 14622600]
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[Full Text: https://doi.org/10.1016/s0092-8674(03)00855-9]
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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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Meyer, L. K., Nichols, K. E.
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<strong>Deciphering genetic uncertainty in familial HLH.</strong>
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Blood 141: 2288-2290, 2023.
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[PubMed: 37166930]
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[Full Text: https://doi.org/10.1182/blood.2023019713]
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</p>
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Noori, T., Rudd-Schmidt, J. A., Kane, A., Frith, K., Gray, P. E., Hu, H., Hsu, D., Chung, C. W. T., Hodel, A. W., Trapani, J. A., Voskoboinik, I.
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<strong>A cell-based functional assay that accurately links genotype to phenotype in familial HLH.</strong>
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Blood 141: 2330-2342, 2023. Note: Erratum: Blood 143: 562 only, 2024.
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[PubMed: 36706356]
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[Full Text: https://doi.org/10.1182/blood.2022018398]
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</p>
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</li>
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<li>
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Ren, Q., Wimmer, C., Chicka, M. C., Ye, S., Ren, Y., Hughson, F. M., Whiteheart, S. W.
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<strong>Munc13-4 is a limiting factor in the pathway required for platelet granule release and hemostasis.</strong>
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Blood 116: 869-877, 2010.
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[PubMed: 20435885]
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[Full Text: https://doi.org/10.1182/blood-2010-02-270934]
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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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Santoro, A., Cannella, S., Bossi, G., Gallo, F., Trizzino, A., Pende, D., Dieli, F., Bruno, G., Stinchcombe, J. C., Micalizzi, C., De Fusco, C., Danesino, C., Moretta, L., Notarangelo, L. D., Griffiths, G. M., Arico, M.
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<strong>Novel Munc13-4 mutations in children and young adult patients with haemophagocytic lymphohistiocytosis. (Letter)</strong>
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J. Med. Genet. 43: 953-960, 2006.
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[PubMed: 16825436]
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[Full Text: https://doi.org/10.1136/jmg.2006.041863]
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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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Shirakawa, R., Higashi, T., Tabuchi, A., Yoshioka, A., Nishioka, H., Fukuda, M., Kita, T., Horiuch, H.
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<strong>Munc13-4 is a GTP-Rab27-binding protein regulating dense core granule secretion in platelets.</strong>
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J. Biol. Chem. 279: 10730-10737, 2004.
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[PubMed: 14699162]
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[Full Text: https://doi.org/10.1074/jbc.M309426200]
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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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Zur Stadt, U., Beutel, K., Kolberg, S., Schneppenheim, R., Kabisch, H., Janka, G., Hennies, H. C.
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<strong>Mutation spectrum in children with primary hemophagocytic lymphohistiocytosis: molecular and functional analyses of PRF1, UNC13D, STX11, and RAB27A.</strong>
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Hum. Mutat. 27: 62-68, 2006.
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[PubMed: 16278825]
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[Full Text: https://doi.org/10.1002/humu.20274]
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</ol>
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Hilary J. Vernon - updated : 06/04/2024<br>Paul J. Converse - updated : 7/1/2011<br>Marla J. F. O'Neill - updated : 11/12/2008<br>Victor A. McKusick - updated : 5/31/2007<br>Victor A. McKusick - updated : 1/20/2006<br>Patricia A. Hartz - updated : 11/5/2004
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Stylianos E. Antonarakis : 9/3/2004
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carol : 01/15/2025<br>carol : 06/05/2024<br>carol : 06/04/2024<br>carol : 09/09/2019<br>carol : 07/19/2017<br>carol : 05/23/2017<br>alopez : 09/09/2015<br>mcolton : 8/3/2015<br>mgross : 7/7/2011<br>mgross : 7/7/2011<br>terry : 7/1/2011<br>wwang : 11/13/2008<br>terry : 11/12/2008<br>alopez : 6/5/2007<br>terry : 5/31/2007<br>alopez : 3/8/2006<br>terry : 1/20/2006<br>mgross : 11/10/2004<br>terry : 11/5/2004<br>mgross : 9/3/2004
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