2988 lines
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Entry
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- *607145 - DYSTROBREVIN-BINDING PROTEIN 1; DTNBP1
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- OMIM
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<p>
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<span class="h4">*607145</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/607145">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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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=ENSG00000047579;t=ENST00000344537" 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=84062" 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=607145" 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 class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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<div 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=ENSG00000047579;t=ENST00000344537" 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_001271667,NM_001271668,NM_001271669,NM_032122,NM_183040,NR_036448,XM_011514937,XM_047419394,XM_047419395" 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_032122" 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=607145" 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=06190&isoform_id=06190_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/DTNBP1" 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/12002004,12052800,15080306,16549166,17834109,19549327,32965400,34304368,38604971,119575763,119575764,119575765,119575766,119575767,119575768,158254872,410651504,410651506,410651508,767940834,957951625,957951628,2217363214,2217363216,2462610762,2462610764,2462610766" 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/Q96EV8" 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=84062" 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=ENSG00000047579;t=ENST00000344537" 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=DTNBP1" 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=DTNBP1" 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+84062" 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/DTNBP1" 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:84062" 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/84062" 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=chr6&hgg_gene=ENST00000344537.10&hgg_start=15522807&hgg_end=15663058&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 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:17328" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=607145[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=607145[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://gnomad.broadinstitute.org/gene/ENSG00000047579" 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=DTNBP1" 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=DTNBP1" 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=DTNBP1" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=DTNBP1&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/PA27512" 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:17328" 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/FBgn0036819.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:2137586" 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/DTNBP1#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:2137586" 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/84062/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=84062" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-040426-1036" 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=DTNBP1&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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607145
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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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DYSTROBREVIN-BINDING PROTEIN 1; DTNBP1
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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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DYSBINDIN<br />
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SANDY, MOUSE, HOMOLOG OF; SDY<br />
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HPS7 GENE; HPS7<br />
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BIOGENESIS OF LYSOSOME-RELATED ORGANELLES COMPLEX 1, SUBUNIT 8; BLOC1S8<br />
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BLOC1, SUBUNIT 8; BLOS8
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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=DTNBP1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">DTNBP1</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/6/87?start=-3&limit=10&highlight=87">6p22.3</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr6:15522807-15663058&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'})">6:15,522,807-15,663,058</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/6/87?start=-3&limit=10&highlight=87">
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6p22.3
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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Hermansky-Pudlak syndrome 7
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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/614076"> 614076 </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>
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<ul class="dropdown-menu" style="width: 17em;">
|
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<li><a href="/graph/linear/607145" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
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<li><a href="/graph/radial/607145" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
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|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
|
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</span>
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</span>
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</h4>
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<div>
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<a id="description" class="mim-anchor"></a>
|
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<div id="mimDescriptionFold" class="collapse in ">
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<span class="mim-text-font">
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<p>The DYNBP1 gene encodes dysbindin, a key component of biogenesis of lysosome-related organelles complex-1 (BLOC-1), which regulates the trafficking of proteins in the lysosomal pathway (summary by <a href="#13" class="mim-tip-reference" title="Tang, T. T.-T., Yang, F., Chen, B.-S., Lu, Y., Ji, Y., Roche, K. W., Lu, B. <strong>Dysbindin regulates hippocampal LTP by controlling NMDA receptor surface expression.</strong> Proc. Nat. Acad. Sci. 106: 21395-21400, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19955431/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19955431</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19955431[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0910499106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19955431">Tang et al., 2009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19955431" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using mouse beta-dystrobrevin (DTNB; <a href="/entry/602415">602415</a>) in a yeast 2-hybrid screen, <a href="#1" class="mim-tip-reference" title="Benson, M. A., Newey, S. E., Martin-Rendon, E., Hawkes, R., Blake, D. J. <strong>Dysbindin, a novel coiled-coil-containing protein that interacts with the dystrobrevins in muscle and brain.</strong> J. Biol. Chem. 276: 24232-24241, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11316798/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11316798</a>] [<a href="https://doi.org/10.1074/jbc.M010418200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11316798">Benson et al. (2001)</a> cloned dysbindin from adult mouse brain and myotube cDNA libraries. The deduced 352-amino acid protein has a calculated molecular mass of about 40 kD and contains a coiled-coil domain. Northern blot analysis revealed variable expression of dysbindin in all mouse tissues examined. Immunostaining of mouse muscle showed colocalization with alpha-dystrobrevin (DTNA; <a href="/entry/601239">601239</a>) at the sarcolemma of most muscle fibers and in large blood vessels. Immunostaining of mouse brain sections revealed dysbindin confined to neurons, with no significant labeling of glial cells. Dysbindin localized primarily in axon bundles and especially in certain axon terminals, notably mossy fiber synaptic terminals in the cerebellum and hippocampus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11316798" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By database analysis, <a href="#12" class="mim-tip-reference" title="Tang, J., LeGros, R. P., Louneva, N., Yeh, L., Cohen, J. W., Hahn, C.-G., Blake, D. J., Arnold, S. E., Talbot, K. <strong>Dysbindin-1 in dorsolateral prefrontal cortex of schizophrenia cases is reduced in an isoform-specific manner unrelated to dysbindin-1 mRNA expression.</strong> Hum. Molec. Genet. 18: 3851-3863, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19617633/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19617633</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19617633[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddp329" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19617633">Tang et al. (2009)</a> identified 3 DTNBP1 splice variants, which they termed dysbindin-1A, -1B, and -1C. The full-length dysbindin-1A contains 351 amino acids. The dysbindin-1B isoform is 303 amino acids and lacks the C-terminal PEST domain, whereas dysbindin-1C is 270 amino acids and lacks the N-terminal region in front of the coiled-coil domain. Tissue fractionation studies on the dorsolateral prefrontal cortex, anterior cingulate gyrus, superior temporal gyrus, and hippocampus showed that dysbindin-1C was concentrated only in synapses with a small amount associated with synaptic vesicles and a large amount in postsynaptic densities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19617633" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using yeast 2-hybrid screens and coimmunoprecipitation experiments, <a href="#1" class="mim-tip-reference" title="Benson, M. A., Newey, S. E., Martin-Rendon, E., Hawkes, R., Blake, D. J. <strong>Dysbindin, a novel coiled-coil-containing protein that interacts with the dystrobrevins in muscle and brain.</strong> J. Biol. Chem. 276: 24232-24241, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11316798/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11316798</a>] [<a href="https://doi.org/10.1074/jbc.M010418200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11316798">Benson et al. (2001)</a> determined that the C terminus of mouse dysbindin interacts directly with both Dtna and Dtnb. Immunolocalization in transfected COS-7 cells indicated diffuse cytoplasmic and nuclear staining that did not colocalize with Dtnb, which was concentrated in perinuclear punctae. When cotransfected, dysbindin expression caused relocalization of Dtnb into a diffuse cytoplasmic pattern. <a href="#1" class="mim-tip-reference" title="Benson, M. A., Newey, S. E., Martin-Rendon, E., Hawkes, R., Blake, D. J. <strong>Dysbindin, a novel coiled-coil-containing protein that interacts with the dystrobrevins in muscle and brain.</strong> J. Biol. Chem. 276: 24232-24241, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11316798/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11316798</a>] [<a href="https://doi.org/10.1074/jbc.M010418200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11316798">Benson et al. (2001)</a> found that dysbindin was significantly upregulated in dystrophin (<a href="/entry/300377">300377</a>)-deficient (mdx) mouse skeletal muscle. Levels of dysbindin in total muscle extracts from mdx mice showed an approximately 5-fold increase when compared with normal muscle, and immunostaining revealed upregulation at the sarcolemma of all fibers coincident with a reduction of intrafiber labeling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11316798" 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>Dysbindin is a ubiquitously expressed protein that binds to alpha- and beta-dystrobrevins, components of the dystrophin-associated protein complex (DPC; see <a href="/entry/602415">602415</a>) in both muscle and nonmuscle cells (<a href="#1" class="mim-tip-reference" title="Benson, M. A., Newey, S. E., Martin-Rendon, E., Hawkes, R., Blake, D. J. <strong>Dysbindin, a novel coiled-coil-containing protein that interacts with the dystrobrevins in muscle and brain.</strong> J. Biol. Chem. 276: 24232-24241, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11316798/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11316798</a>] [<a href="https://doi.org/10.1074/jbc.M010418200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11316798">Benson et al., 2001</a>). <a href="#6" class="mim-tip-reference" title="Li, W., Zhang, Q., Oiso, N., Novak, E. K., Gautam, R., O'Brien, E. P., Tinsley, C. L., Blake, D. J., Spritz, R. A., Copeland, N. G., Jenkins, N. A., Amato, D., Roe, B. A., Starcevic, M., Dell'Angelica, E. C., Elliott, R. W., Mishra, V., Kingsmore, S. F., Paylor, R. E., Swank, R. T. <strong>Hermansky-Pudlak syndrome type 7 (HPS-7) results from mutant dysbindin, a member of the biogenesis of lysosome-related organelles complex 1 (BLOC-1).</strong> Nature Genet. 35: 84-89, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12923531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12923531</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12923531[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng1229" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12923531">Li et al. (2003)</a> showed that dysbindin is a component of the biogenesis of lysosome-related organelles complex-1 (BLOC1), which regulates trafficking to lysosome-related organelles and includes the proteins pallidin (PLDN; <a href="/entry/604310">604310</a>), muted (MU; <a href="/entry/607289">607289</a>), and cappuccino (CNO; <a href="/entry/605695">605695</a>). These proteins are associated with Hermansky-Pudlak syndrome (HPS; <a href="/entry/203300">203300</a>) in mice; <a href="#6" class="mim-tip-reference" title="Li, W., Zhang, Q., Oiso, N., Novak, E. K., Gautam, R., O'Brien, E. P., Tinsley, C. L., Blake, D. J., Spritz, R. A., Copeland, N. G., Jenkins, N. A., Amato, D., Roe, B. A., Starcevic, M., Dell'Angelica, E. C., Elliott, R. W., Mishra, V., Kingsmore, S. F., Paylor, R. E., Swank, R. T. <strong>Hermansky-Pudlak syndrome type 7 (HPS-7) results from mutant dysbindin, a member of the biogenesis of lysosome-related organelles complex 1 (BLOC-1).</strong> Nature Genet. 35: 84-89, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12923531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12923531</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12923531[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng1229" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12923531">Li et al. (2003)</a> found mutation in the human DTNBP1 gene in an individual with HPS. The findings of <a href="#6" class="mim-tip-reference" title="Li, W., Zhang, Q., Oiso, N., Novak, E. K., Gautam, R., O'Brien, E. P., Tinsley, C. L., Blake, D. J., Spritz, R. A., Copeland, N. G., Jenkins, N. A., Amato, D., Roe, B. A., Starcevic, M., Dell'Angelica, E. C., Elliott, R. W., Mishra, V., Kingsmore, S. F., Paylor, R. E., Swank, R. T. <strong>Hermansky-Pudlak syndrome type 7 (HPS-7) results from mutant dysbindin, a member of the biogenesis of lysosome-related organelles complex 1 (BLOC-1).</strong> Nature Genet. 35: 84-89, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12923531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12923531</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12923531[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng1229" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12923531">Li et al. (2003)</a> showed that BLOC1 is important in producing the HPS phenotype in humans, indicated that dysbindin has a role in the biogenesis of lysosome-related organelles, and identified unexpected interactions between components of DPC and BLOC1. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12923531+11316798" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By in situ hybridization, <a href="#11" class="mim-tip-reference" title="Talbot, K., Eidem, W. L., Tinsley, C. L., Benson, M. A., Thompson, E. W., Smith, R. J., Hahn, C.-G., Siegel, S. J., Trojanowski, J. Q., Gur, R. E., Blake, D. J., Arnold, S. E. <strong>Dysbindin-1 is reduced in intrinsic, glutamatergic terminals of the hippocampal formation in schizophrenia.</strong> J. Clin. Invest. 113: 1353-1363, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15124027/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15124027</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15124027[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/10.1172/JCI20425" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15124027">Talbot et al. (2004)</a> found dysbindin-1 expression in all principal neuronal populations of the hippocampus, including pyramidal cells, granule cells, and polymorph cells. The dysbindin-1 protein was located in presynaptic axon terminals of glutamatergic pathways. In schizophrenia (see <a href="/entry/181500">181500</a>) cases, there was a significant reduction of dysbindin-1 in the terminal fields of intrinsic glutamatergic connections of the hippocampus compared to controls, although reductions were not seen in other brain areas, such as the anterior cingulate cortex. The reduction of presynaptic dysbindin-1 was independent of beta-dystrobrevin and the dystrophin glycoprotein complex. <a href="#11" class="mim-tip-reference" title="Talbot, K., Eidem, W. L., Tinsley, C. L., Benson, M. A., Thompson, E. W., Smith, R. J., Hahn, C.-G., Siegel, S. J., Trojanowski, J. Q., Gur, R. E., Blake, D. J., Arnold, S. E. <strong>Dysbindin-1 is reduced in intrinsic, glutamatergic terminals of the hippocampal formation in schizophrenia.</strong> J. Clin. Invest. 113: 1353-1363, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15124027/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15124027</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15124027[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/10.1172/JCI20425" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15124027">Talbot et al. (2004)</a> suggested that the changes may contribute to the cognitive defects in schizophrenia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15124027" 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 rat cortical neurons, <a href="#9" class="mim-tip-reference" title="Numakawa, T., Yagasaki, Y., Ishimoto, T., Okada, T., Suzuki, T., Iwata, N., Ozaki, N., Taguchi, T., Tatsumi, M., Kamijima, K., Straub, R. E., Weinberger, D. R., Kunugi, H., Hashimoto, R. <strong>Evidence of novel neuronal functions of dysbindin, a susceptibility gene for schizophrenia.</strong> Hum. Molec. Genet. 13: 2699-2708, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15345706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15345706</a>] [<a href="https://doi.org/10.1093/hmg/ddh280" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15345706">Numakawa et al. (2004)</a> showed that overexpression of dysbindin induced expression of 2 presynaptic proteins, SNAP25 (<a href="/entry/600322">600322</a>) and synapsin I (SYN1; <a href="/entry/313440">313440</a>), and increased extracellular basal glutamate levels and release of glutamate evoked by high potassium. Conversely, knockdown of endogenous dysbindin protein by small interfering RNA (siRNA) resulted in reduction of presynaptic protein expression and glutamate release, suggesting that dysbindin might influence exocytotic glutamate release via upregulation of the molecules in presynaptic machinery. Overexpression of dysbindin increased phosphorylation of Akt (<a href="/entry/164730">164730</a>) and protected cortical neurons against neuronal death due to serum deprivation; these effects were blocked by a phosphatidylinositol 3-kinase (PI3-kinase) inhibitor. SiRNA-mediated silencing of dysbindin protein diminished Akt phosphorylation and facilitated neuronal death induced by serum deprivation, suggesting that dysbindin may promote neuronal viability through PI3-kinase-Akt signaling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15345706" 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>To better understand how neural function is stabilized during development and throughout life, <a href="#3" class="mim-tip-reference" title="Dickman, D. K., Davis, G. W. <strong>The schizophrenia susceptibility gene dysbindin controls synaptic homeostasis.</strong> Science 326: 1127-1130, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19965435/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19965435</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19965435[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1179685" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19965435">Dickman and Davis (2009)</a> used an electrophysiology-based forward genetic screen and assessed the function of more than 250 neuronally expressed genes for a role in the homeostatic modulation of synaptic transmission in Drosophila. This screen ruled out the involvement of numerous synaptic proteins and identified a critical function for dysbindin, a gene linked to schizophrenia in humans (see <a href="/entry/600511">600511</a>). <a href="#3" class="mim-tip-reference" title="Dickman, D. K., Davis, G. W. <strong>The schizophrenia susceptibility gene dysbindin controls synaptic homeostasis.</strong> Science 326: 1127-1130, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19965435/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19965435</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19965435[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1179685" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19965435">Dickman and Davis (2009)</a> found that dysbindin is required presynaptically for the retrograde, homeostatic modulation of neurotransmission, and functions in a dose-dependent manner downstream or independently of calcium influx. Thus, <a href="#3" class="mim-tip-reference" title="Dickman, D. K., Davis, G. W. <strong>The schizophrenia susceptibility gene dysbindin controls synaptic homeostasis.</strong> Science 326: 1127-1130, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19965435/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19965435</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19965435[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1179685" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19965435">Dickman and Davis (2009)</a> concluded that dysbindin is essential for adaptive neural plasticity and may link altered homeostatic signaling with a complex neurologic disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19965435" 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="Locke, M., Tinsley, C. L., Benson, M. A., Blake, D. J. <strong>TRIM32 is an E3 ubiquitin ligase for dysbindin.</strong> Hum. Molec. Genet. 18: 2344-2358, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19349376/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19349376</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19349376[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddp167" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19349376">Locke et al. (2009)</a> showed that TRIM32 is a widely expressed ubiquitin ligase that is localized to the Z-line in skeletal muscle. TRIM32 bound and ubiquitinated dysbindin, augmenting its degradation. Knockdown of TRIM32 in myoblasts resulted in elevated levels of dysbindin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19349376" 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 brain samples from 28 Caucasian schizophrenia patients and 28 age- and sex-matched controls, <a href="#12" class="mim-tip-reference" title="Tang, J., LeGros, R. P., Louneva, N., Yeh, L., Cohen, J. W., Hahn, C.-G., Blake, D. J., Arnold, S. E., Talbot, K. <strong>Dysbindin-1 in dorsolateral prefrontal cortex of schizophrenia cases is reduced in an isoform-specific manner unrelated to dysbindin-1 mRNA expression.</strong> Hum. Molec. Genet. 18: 3851-3863, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19617633/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19617633</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19617633[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddp329" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19617633">Tang et al. (2009)</a> reported that Western blotting of whole-tissue lysates of dorsolateral prefrontal cortex (DLPFC) revealed significant reductions in dysbindin-1C (but not in dysbindin-1A or -1B) in schizophrenia (p = 0.022). These reductions occurred without any significant change in levels of the encoding transcript in the same tissue samples and in the absence of the only DTNBP1 risk haplotype for schizophrenia reported in the United States (see <a href="#4" class="mim-tip-reference" title="Funke, B., Finn, C. T., Plocik, A. M., Lake, S., DeRosse, P., Kane, J. M., Kucherlapati, R., Malhotra, A. K. <strong>Association of the DTNBP1 locus with schizophrenia in a U.S. population.</strong> Am. J. Hum. Genet. 75: 891-898, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15362017/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15362017</a>] [<a href="https://doi.org/10.1086/425279" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15362017">Funke et al. (2004)</a> and <a href="/entry/600511">600511</a>). No significant correlations were found between case-control differences in any dysbindin-1 isoform and the case-control differences in its encoding mRNA. The mean 60% decrease in dysbindin-1C observed in 71% of the case-control pairs appeared to reflect abnormalities in mRNA translation and/or processes promoting dysbindin-1C degradation. Given the predominantly postsynaptic localization of dysbindin-1C and known postsynaptic effects of dysbindin-1 reductions in the rodent equivalent of the DLPFC, <a href="#12" class="mim-tip-reference" title="Tang, J., LeGros, R. P., Louneva, N., Yeh, L., Cohen, J. W., Hahn, C.-G., Blake, D. J., Arnold, S. E., Talbot, K. <strong>Dysbindin-1 in dorsolateral prefrontal cortex of schizophrenia cases is reduced in an isoform-specific manner unrelated to dysbindin-1 mRNA expression.</strong> Hum. Molec. Genet. 18: 3851-3863, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19617633/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19617633</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19617633[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddp329" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19617633">Tang et al. (2009)</a> suggested that decreased dysbindin-1C in the DLPFC may contribute to the cognitive deficits of schizophrenia by promoting NMDA receptor hypofunction in fast-spiking interneurons. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19617633+15362017" 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="#5" class="mim-tip-reference" title="Gross, M. B. <strong>Personal Communication.</strong> Baltimore, Md. 2/17/2015."None>Gross (2015)</a> mapped the DTNBP1 gene to chromosome 6p22.3 based on an alignment of the DTNBP1 sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=AF061734" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">AF061734</a>) with the genomic sequence (GRCh38).</p>
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<a href="#6" class="mim-tip-reference" title="Li, W., Zhang, Q., Oiso, N., Novak, E. K., Gautam, R., O'Brien, E. P., Tinsley, C. L., Blake, D. J., Spritz, R. A., Copeland, N. G., Jenkins, N. A., Amato, D., Roe, B. A., Starcevic, M., Dell'Angelica, E. C., Elliott, R. W., Mishra, V., Kingsmore, S. F., Paylor, R. E., Swank, R. T. <strong>Hermansky-Pudlak syndrome type 7 (HPS-7) results from mutant dysbindin, a member of the biogenesis of lysosome-related organelles complex 1 (BLOC-1).</strong> Nature Genet. 35: 84-89, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12923531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12923531</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12923531[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng1229" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12923531">Li et al. (2003)</a> screened for mutations in the 10 exons of the DTNBP1 gene in 22 unrelated non-Puerto Rican individuals with Hermansky-Pudlak syndrome (HPS) who did not have mutations in HPS1 (<a href="/entry/604982">604982</a>), HPS3 (<a href="/entry/606118">606118</a>), HPS4 (<a href="/entry/606682">606682</a>), HPS5 (<a href="/entry/607521">607521</a>), or HPS6 (<a href="/entry/607522">607522</a>). In a Portuguese woman with HPS7 (<a href="/entry/614076">614076</a>), they found homozygosity for a truncating mutation in the DTNBP1 gene (Q103X; <a href="#0001">607145.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12923531" 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 77-year-old Caucasian woman, born of consanguineous parents, with HPS7, <a href="#8" class="mim-tip-reference" title="Lowe, G. C., Sanchez Guiu, I., Chapman, O., Rivera, J., Lordkipanidze, M., Dovlatova, N., Wilde, J., Watson, S. P., Morgan, N. V. <strong>Microsatellite markers as a rapid approach for autozygosity mapping in Hermansky-Pudlak syndrome: identification of the second HPS7 mutation in a patient presenting late in life. (Letter)</strong> Thromb. Haemost. 109: 766-768, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23364359/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23364359</a>] [<a href="https://doi.org/10.1160/TH12-11-0876" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23364359">Lowe et al. (2013)</a> identified a homozygous truncating mutation in the DTNBP1 gene (W59X; <a href="#0002">607145.0002</a>). The mutation was found by autozygosity mapping with microsatellite markers followed by direct sequencing of the candidate DTNBP1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23364359" 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 6-year-old Paraguayan boy with HPS7, <a href="#2" class="mim-tip-reference" title="Bryan, M. M., Tolman, N. J., Simon, K. L., Huizing, M., Hufnagel, R. B., Brooks, B. P., Speransky, V., Mullikin, J. C., Gahl, W. A., Malicdan, M. C. V., Gochuico, B. R. <strong>Clinical and molecular phenotyping of a child with Hermansky-Pudlak syndrome-7, an uncommon genetic type of HPS.</strong> Molec. Genet. Metab. 120: 378-383, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28259707/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28259707</a>] [<a href="https://doi.org/10.1016/j.ymgme.2017.02.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28259707">Bryan et al. (2017)</a> identified homozygosity for the previously identified Q103X mutation in the DTNBP1 gene. Patient fibroblasts showed normal DTNBP1 mRNA expression but negligible dysbindin protein expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28259707" 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>Association of DTNBP1 with Schizophrenia Risk</em></strong></p><p>
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For a discussion of the relationship between variation in the DTNBP1 gene and risk of schizophrenia, see SCZD3 (<a href="/entry/600511">600511</a>).</p>
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<p>Hermansky-Pudlak syndrome (<a href="/entry/203300">203300</a>) is a genetically heterogeneous disorder characterized by oculocutaneous albinism, prolonged bleeding, and pulmonary fibrosis due to abnormal vesicle trafficking to lysosomes and related organelles such as melanosomes and platelet-dense granules. In mice, at least 16 loci are associated with HPS, including 'sandy' (sdy) (<a href="#10" class="mim-tip-reference" title="Swank, R. T., Sweet, H. O., Davisson, M. T., Reddington, M., Novak, E. K. <strong>Sandy: a new mouse model for platelet storage pool deficiency.</strong> Genet. Res. 58: 51-62, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1936982/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1936982</a>] [<a href="https://doi.org/10.1017/s0016672300029608" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1936982">Swank et al., 1991</a>). <a href="#6" class="mim-tip-reference" title="Li, W., Zhang, Q., Oiso, N., Novak, E. K., Gautam, R., O'Brien, E. P., Tinsley, C. L., Blake, D. J., Spritz, R. A., Copeland, N. G., Jenkins, N. A., Amato, D., Roe, B. A., Starcevic, M., Dell'Angelica, E. C., Elliott, R. W., Mishra, V., Kingsmore, S. F., Paylor, R. E., Swank, R. T. <strong>Hermansky-Pudlak syndrome type 7 (HPS-7) results from mutant dysbindin, a member of the biogenesis of lysosome-related organelles complex 1 (BLOC-1).</strong> Nature Genet. 35: 84-89, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12923531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12923531</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12923531[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng1229" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12923531">Li et al. (2003)</a> showed that the sdy mutant mouse expresses no dysbindin protein owing to a deletion in the gene Dtnbp1. They confirmed that mutation of dysbindin causes the sdy phenotype and that dysbindin is important for normal platelet-dense granule and melanosome biogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1936982+12923531" 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="#13" class="mim-tip-reference" title="Tang, T. T.-T., Yang, F., Chen, B.-S., Lu, Y., Ji, Y., Roche, K. W., Lu, B. <strong>Dysbindin regulates hippocampal LTP by controlling NMDA receptor surface expression.</strong> Proc. Nat. Acad. Sci. 106: 21395-21400, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19955431/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19955431</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19955431[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0910499106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19955431">Tang et al. (2009)</a> found that hippocampal neurons derived from Dtnbp1-null mice had about a 50% increase in surface expression of Nr2a (<a href="/entry/138253">138253</a>), a subunit of the tetrameric NMDA receptor, compared to control, whereas surface expression of Nr2b (<a href="/entry/138252">138252</a>) was unaffected. Western blot analysis showed no difference in levels of these proteins in the adult hippocampus of mutant mice compared to wildtype. Expression of dysbindin reduced Nr2a surface expression in both wildtype and Dtnbp1-null neurons. Electrophysiologic recordings of Dtnbp1-null hippocampal slices showed an increase in NMDA receptor excitatory postsynaptic currents mediated by Nr2a as well as an increase in long-term potentiation, suggesting an alteration in synaptic plasticity in the hippocampus. Basal synaptic transmission and long-term depression were normal. The findings suggested that murine dysbindin controls hippocampal long-term potentiation by selective and direct regulation of the surface expression of Nr2a. <a href="#13" class="mim-tip-reference" title="Tang, T. T.-T., Yang, F., Chen, B.-S., Lu, Y., Ji, Y., Roche, K. W., Lu, B. <strong>Dysbindin regulates hippocampal LTP by controlling NMDA receptor surface expression.</strong> Proc. Nat. Acad. Sci. 106: 21395-21400, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19955431/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19955431</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19955431[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0910499106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19955431">Tang et al. (2009)</a> noted that Nr2a undergoes postendocytic sorting through the lysosomal pathway. They suggested that knockout of dysbindin may divert endocytosed membrane proteins back to the cell surface rather than to the lysosome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19955431" 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> rs104893945 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893945;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/rs104893945?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=rs104893945" 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=rs104893945" 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=RCV000003601 OR RCV002512713" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000003601, RCV002512713" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000003601...</a>
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<p>In a 48-year-old Portuguese woman with Hermansky-Pudlak syndrome (HPS7; <a href="/entry/614076">614076</a>), <a href="#6" class="mim-tip-reference" title="Li, W., Zhang, Q., Oiso, N., Novak, E. K., Gautam, R., O'Brien, E. P., Tinsley, C. L., Blake, D. J., Spritz, R. A., Copeland, N. G., Jenkins, N. A., Amato, D., Roe, B. A., Starcevic, M., Dell'Angelica, E. C., Elliott, R. W., Mishra, V., Kingsmore, S. F., Paylor, R. E., Swank, R. T. <strong>Hermansky-Pudlak syndrome type 7 (HPS-7) results from mutant dysbindin, a member of the biogenesis of lysosome-related organelles complex 1 (BLOC-1).</strong> Nature Genet. 35: 84-89, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12923531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12923531</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12923531[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng1229" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12923531">Li et al. (2003)</a> found homozygosity for a 307C-T transition in the DTNBP1 gene resulting in the amino acid substitution gln103 to ter (Q103X) in homozygous state. Bleeding time was 13 minutes, and platelet aggregation indicated a storage-pool deficiency. The woman had mild shortness of breath on exertion and reduced lung compliance but otherwise normal pulmonary function and high resolution computed tomography (CT) chest scans, and had no muscle weakness or ataxia. Her parents were first cousins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12923531" 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 6-year-old Paraguayan boy with HPS in whom no mutations in other genes associated with HPS were found, <a href="#2" class="mim-tip-reference" title="Bryan, M. M., Tolman, N. J., Simon, K. L., Huizing, M., Hufnagel, R. B., Brooks, B. P., Speransky, V., Mullikin, J. C., Gahl, W. A., Malicdan, M. C. V., Gochuico, B. R. <strong>Clinical and molecular phenotyping of a child with Hermansky-Pudlak syndrome-7, an uncommon genetic type of HPS.</strong> Molec. Genet. Metab. 120: 378-383, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28259707/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28259707</a>] [<a href="https://doi.org/10.1016/j.ymgme.2017.02.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28259707">Bryan et al. (2017)</a> identified homozygosity for the Q103X mutation in the DTNBP1 gene. The mutation was found by exome sequencing and confirmed by Sanger sequencing. DNA of the parents was not tested. Patient fibroblasts showed normal DTNBP1 mRNA levels but markedly reduced dysbindin protein expression. The authors noted that the Q103X mutation had a low frequency in the ExAC database, being reported in only 2 of 120,818 alleles from multiple populations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28259707" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0002 HERMANSKY-PUDLAK SYNDROME 7</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> rs727502866 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs727502866;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/rs727502866?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=rs727502866" 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=rs727502866" 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=RCV000150041" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000150041" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000150041</a>
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<p>In a 77-year-old Caucasian woman, born of consanguineous parents, with Hermansky-Pudlak syndrome-7 (HPS7; <a href="/entry/614076">614076</a>), <a href="#8" class="mim-tip-reference" title="Lowe, G. C., Sanchez Guiu, I., Chapman, O., Rivera, J., Lordkipanidze, M., Dovlatova, N., Wilde, J., Watson, S. P., Morgan, N. V. <strong>Microsatellite markers as a rapid approach for autozygosity mapping in Hermansky-Pudlak syndrome: identification of the second HPS7 mutation in a patient presenting late in life. (Letter)</strong> Thromb. Haemost. 109: 766-768, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23364359/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23364359</a>] [<a href="https://doi.org/10.1160/TH12-11-0876" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23364359">Lowe et al. (2013)</a> identified a homozygous c.177G-A transition in exon 4 of the DTNBP1 gene, resulting in a trp59-to-ter (W59X) substitution. The mutation was found by autozygosity mapping with microsatellite markers followed by direct sequencing of the candidate DTNBP1 gene. The patient had a lifelong bleeding tendency, pale skin and hair, and lifelong reduced visual acuity and nystagmus. She had no evidence of pulmonary disease but did have granulomatous colitis diagnosed as Crohn disease. Platelet studies showed impaired aggregation responses and a lack of dense granule secretion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23364359" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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Benson, M. A., Newey, S. E., Martin-Rendon, E., Hawkes, R., Blake, D. J.
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<strong>Dysbindin, a novel coiled-coil-containing protein that interacts with the dystrobrevins in muscle and brain.</strong>
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J. Biol. Chem. 276: 24232-24241, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11316798/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11316798</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11316798" 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.M010418200" target="_blank">Full Text</a>]
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Bryan, M. M., Tolman, N. J., Simon, K. L., Huizing, M., Hufnagel, R. B., Brooks, B. P., Speransky, V., Mullikin, J. C., Gahl, W. A., Malicdan, M. C. V., Gochuico, B. R.
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<strong>Clinical and molecular phenotyping of a child with Hermansky-Pudlak syndrome-7, an uncommon genetic type of HPS.</strong>
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Molec. Genet. Metab. 120: 378-383, 2017.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28259707/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28259707</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28259707" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ymgme.2017.02.007" target="_blank">Full Text</a>]
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Dickman, D. K., Davis, G. W.
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<strong>The schizophrenia susceptibility gene dysbindin controls synaptic homeostasis.</strong>
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Science 326: 1127-1130, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19965435/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19965435</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19965435[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=19965435" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.1179685" target="_blank">Full Text</a>]
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<a id="Funke2004" class="mim-anchor"></a>
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Funke, B., Finn, C. T., Plocik, A. M., Lake, S., DeRosse, P., Kane, J. M., Kucherlapati, R., Malhotra, A. K.
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<strong>Association of the DTNBP1 locus with schizophrenia in a U.S. population.</strong>
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Am. J. Hum. Genet. 75: 891-898, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15362017/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15362017</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15362017" 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/10.1086/425279" target="_blank">Full Text</a>]
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Baltimore, Md. 2/17/2015.
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Li, W., Zhang, Q., Oiso, N., Novak, E. K., Gautam, R., O'Brien, E. P., Tinsley, C. L., Blake, D. J., Spritz, R. A., Copeland, N. G., Jenkins, N. A., Amato, D., Roe, B. A., Starcevic, M., Dell'Angelica, E. C., Elliott, R. W., Mishra, V., Kingsmore, S. F., Paylor, R. E., Swank, R. T.
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<strong>Hermansky-Pudlak syndrome type 7 (HPS-7) results from mutant dysbindin, a member of the biogenesis of lysosome-related organelles complex 1 (BLOC-1).</strong>
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Nature Genet. 35: 84-89, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12923531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12923531</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12923531[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=12923531" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng1229" target="_blank">Full Text</a>]
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Locke, M., Tinsley, C. L., Benson, M. A., Blake, D. J.
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<strong>TRIM32 is an E3 ubiquitin ligase for dysbindin.</strong>
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Hum. Molec. Genet. 18: 2344-2358, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19349376/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19349376</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19349376[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=19349376" 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/10.1093/hmg/ddp167" target="_blank">Full Text</a>]
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Lowe, G. C., Sanchez Guiu, I., Chapman, O., Rivera, J., Lordkipanidze, M., Dovlatova, N., Wilde, J., Watson, S. P., Morgan, N. V.
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<strong>Microsatellite markers as a rapid approach for autozygosity mapping in Hermansky-Pudlak syndrome: identification of the second HPS7 mutation in a patient presenting late in life. (Letter)</strong>
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Thromb. Haemost. 109: 766-768, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23364359/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23364359</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23364359" 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/10.1160/TH12-11-0876" target="_blank">Full Text</a>]
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Numakawa, T., Yagasaki, Y., Ishimoto, T., Okada, T., Suzuki, T., Iwata, N., Ozaki, N., Taguchi, T., Tatsumi, M., Kamijima, K., Straub, R. E., Weinberger, D. R., Kunugi, H., Hashimoto, R.
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<strong>Evidence of novel neuronal functions of dysbindin, a susceptibility gene for schizophrenia.</strong>
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Hum. Molec. Genet. 13: 2699-2708, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15345706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15345706</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15345706" 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/10.1093/hmg/ddh280" 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="10" class="mim-anchor"></a>
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<a id="Swank1991" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Swank, R. T., Sweet, H. O., Davisson, M. T., Reddington, M., Novak, E. K.
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<strong>Sandy: a new mouse model for platelet storage pool deficiency.</strong>
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Genet. Res. 58: 51-62, 1991.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1936982/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1936982</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1936982" 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/10.1017/s0016672300029608" target="_blank">Full Text</a>]
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<a id="11" class="mim-anchor"></a>
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<a id="Talbot2004" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Talbot, K., Eidem, W. L., Tinsley, C. L., Benson, M. A., Thompson, E. W., Smith, R. J., Hahn, C.-G., Siegel, S. J., Trojanowski, J. Q., Gur, R. E., Blake, D. J., Arnold, S. E.
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<strong>Dysbindin-1 is reduced in intrinsic, glutamatergic terminals of the hippocampal formation in schizophrenia.</strong>
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J. Clin. Invest. 113: 1353-1363, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15124027/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15124027</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15124027[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=15124027" 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/10.1172/JCI20425" 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="12" class="mim-anchor"></a>
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<a id="Tang2009" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tang, J., LeGros, R. P., Louneva, N., Yeh, L., Cohen, J. W., Hahn, C.-G., Blake, D. J., Arnold, S. E., Talbot, K.
|
|
<strong>Dysbindin-1 in dorsolateral prefrontal cortex of schizophrenia cases is reduced in an isoform-specific manner unrelated to dysbindin-1 mRNA expression.</strong>
|
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Hum. Molec. Genet. 18: 3851-3863, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19617633/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19617633</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19617633[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=19617633" 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/10.1093/hmg/ddp329" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="13" class="mim-anchor"></a>
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<a id="Tang2009" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tang, T. T.-T., Yang, F., Chen, B.-S., Lu, Y., Ji, Y., Roche, K. W., Lu, B.
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<strong>Dysbindin regulates hippocampal LTP by controlling NMDA receptor surface expression.</strong>
|
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Proc. Nat. Acad. Sci. 106: 21395-21400, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19955431/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19955431</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19955431[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=19955431" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.0910499106" target="_blank">Full Text</a>]
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</p>
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</ol>
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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="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 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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Michael Muriello - updated : 02/02/2018
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Matthew B. Gross - updated : 2/17/2015<br>Cassandra L. Kniffin - updated : 1/21/2015<br>Cassandra L. Kniffin - updated : 9/25/2013<br>George E. Tiller - updated : 8/6/2010<br>George E. Tiller - updated : 3/30/2010<br>Ada Hamosh - updated : 12/29/2009<br>George E. Tiller - updated : 11/17/2008<br>Ada Hamosh - updated : 8/19/2008<br>George E. Tiller - updated : 6/13/2007<br>Victor A. McKusick - updated : 10/10/2006<br>John Logan Black, III - updated : 7/13/2006<br>John Logan Black, III - updated : 4/6/2006<br>Victor A. McKusick - updated : 11/1/2004<br>John Logan Black, III - updated : 7/8/2004<br>Cassandra L. Kniffin - updated : 6/28/2004<br>Victor A. McKusick - updated : 12/18/2003<br>Victor A. McKusick - updated : 8/21/2003<br>Victor A. McKusick - updated : 1/22/2003<br>Victor A. McKusick - updated : 9/27/2002
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</span>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Patricia A. Hartz : 8/13/2002
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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<div 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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alopez : 11/20/2020
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 02/05/2018<br>carol : 02/02/2018<br>carol : 03/02/2017<br>carol : 02/28/2017<br>alopez : 06/23/2016<br>mgross : 2/17/2015<br>carol : 1/22/2015<br>mcolton : 1/21/2015<br>ckniffin : 1/21/2015<br>carol : 11/26/2014<br>carol : 10/10/2013<br>tpirozzi : 10/10/2013<br>ckniffin : 9/25/2013<br>mgross : 4/15/2013<br>alopez : 7/1/2011<br>alopez : 7/1/2011<br>alopez : 6/30/2011<br>joanna : 2/14/2011<br>wwang : 8/10/2010<br>terry : 8/6/2010<br>wwang : 3/31/2010<br>terry : 3/30/2010<br>alopez : 1/6/2010<br>terry : 12/29/2009<br>wwang : 11/18/2008<br>wwang : 11/17/2008<br>carol : 8/19/2008<br>wwang : 6/18/2007<br>terry : 6/13/2007<br>carol : 5/10/2007<br>carol : 10/10/2006<br>terry : 10/10/2006<br>carol : 7/17/2006<br>carol : 7/14/2006<br>terry : 7/13/2006<br>carol : 4/7/2006<br>terry : 4/6/2006<br>terry : 11/4/2004<br>alopez : 11/4/2004<br>terry : 11/1/2004<br>tkritzer : 7/8/2004<br>tkritzer : 7/8/2004<br>tkritzer : 7/8/2004<br>tkritzer : 7/1/2004<br>ckniffin : 6/28/2004<br>cwells : 12/23/2003<br>terry : 12/18/2003<br>mgross : 9/10/2003<br>alopez : 9/2/2003<br>alopez : 8/22/2003<br>terry : 8/21/2003<br>carol : 7/11/2003<br>tkritzer : 1/24/2003<br>tkritzer : 1/24/2003<br>terry : 1/22/2003<br>carol : 1/21/2003<br>carol : 9/27/2002<br>carol : 9/27/2002<br>mgross : 8/13/2002
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</span>
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</div>
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<div class="container visible-print-block">
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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> 607145
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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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DYSTROBREVIN-BINDING PROTEIN 1; DTNBP1
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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<div>
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<h4>
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<span class="mim-font">
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DYSBINDIN<br />
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SANDY, MOUSE, HOMOLOG OF; SDY<br />
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HPS7 GENE; HPS7<br />
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BIOGENESIS OF LYSOSOME-RELATED ORGANELLES COMPLEX 1, SUBUNIT 8; BLOC1S8<br />
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BLOC1, SUBUNIT 8; BLOS8
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</span>
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</h4>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: DTNBP1</em></strong>
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</span>
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</p>
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</div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 6p22.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 6:15,522,807-15,663,058 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
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6p22.3
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</td>
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<td>
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<span class="mim-font">
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Hermansky-Pudlak syndrome 7
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</td>
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<td>
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<span class="mim-font">
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614076
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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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<br />
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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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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The DYNBP1 gene encodes dysbindin, a key component of biogenesis of lysosome-related organelles complex-1 (BLOC-1), which regulates the trafficking of proteins in the lysosomal pathway (summary by Tang et al., 2009). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Using mouse beta-dystrobrevin (DTNB; 602415) in a yeast 2-hybrid screen, Benson et al. (2001) cloned dysbindin from adult mouse brain and myotube cDNA libraries. The deduced 352-amino acid protein has a calculated molecular mass of about 40 kD and contains a coiled-coil domain. Northern blot analysis revealed variable expression of dysbindin in all mouse tissues examined. Immunostaining of mouse muscle showed colocalization with alpha-dystrobrevin (DTNA; 601239) at the sarcolemma of most muscle fibers and in large blood vessels. Immunostaining of mouse brain sections revealed dysbindin confined to neurons, with no significant labeling of glial cells. Dysbindin localized primarily in axon bundles and especially in certain axon terminals, notably mossy fiber synaptic terminals in the cerebellum and hippocampus. </p><p>By database analysis, Tang et al. (2009) identified 3 DTNBP1 splice variants, which they termed dysbindin-1A, -1B, and -1C. The full-length dysbindin-1A contains 351 amino acids. The dysbindin-1B isoform is 303 amino acids and lacks the C-terminal PEST domain, whereas dysbindin-1C is 270 amino acids and lacks the N-terminal region in front of the coiled-coil domain. Tissue fractionation studies on the dorsolateral prefrontal cortex, anterior cingulate gyrus, superior temporal gyrus, and hippocampus showed that dysbindin-1C was concentrated only in synapses with a small amount associated with synaptic vesicles and a large amount in postsynaptic densities. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Using yeast 2-hybrid screens and coimmunoprecipitation experiments, Benson et al. (2001) determined that the C terminus of mouse dysbindin interacts directly with both Dtna and Dtnb. Immunolocalization in transfected COS-7 cells indicated diffuse cytoplasmic and nuclear staining that did not colocalize with Dtnb, which was concentrated in perinuclear punctae. When cotransfected, dysbindin expression caused relocalization of Dtnb into a diffuse cytoplasmic pattern. Benson et al. (2001) found that dysbindin was significantly upregulated in dystrophin (300377)-deficient (mdx) mouse skeletal muscle. Levels of dysbindin in total muscle extracts from mdx mice showed an approximately 5-fold increase when compared with normal muscle, and immunostaining revealed upregulation at the sarcolemma of all fibers coincident with a reduction of intrafiber labeling. </p><p>Dysbindin is a ubiquitously expressed protein that binds to alpha- and beta-dystrobrevins, components of the dystrophin-associated protein complex (DPC; see 602415) in both muscle and nonmuscle cells (Benson et al., 2001). Li et al. (2003) showed that dysbindin is a component of the biogenesis of lysosome-related organelles complex-1 (BLOC1), which regulates trafficking to lysosome-related organelles and includes the proteins pallidin (PLDN; 604310), muted (MU; 607289), and cappuccino (CNO; 605695). These proteins are associated with Hermansky-Pudlak syndrome (HPS; 203300) in mice; Li et al. (2003) found mutation in the human DTNBP1 gene in an individual with HPS. The findings of Li et al. (2003) showed that BLOC1 is important in producing the HPS phenotype in humans, indicated that dysbindin has a role in the biogenesis of lysosome-related organelles, and identified unexpected interactions between components of DPC and BLOC1. </p><p>By in situ hybridization, Talbot et al. (2004) found dysbindin-1 expression in all principal neuronal populations of the hippocampus, including pyramidal cells, granule cells, and polymorph cells. The dysbindin-1 protein was located in presynaptic axon terminals of glutamatergic pathways. In schizophrenia (see 181500) cases, there was a significant reduction of dysbindin-1 in the terminal fields of intrinsic glutamatergic connections of the hippocampus compared to controls, although reductions were not seen in other brain areas, such as the anterior cingulate cortex. The reduction of presynaptic dysbindin-1 was independent of beta-dystrobrevin and the dystrophin glycoprotein complex. Talbot et al. (2004) suggested that the changes may contribute to the cognitive defects in schizophrenia. </p><p>In rat cortical neurons, Numakawa et al. (2004) showed that overexpression of dysbindin induced expression of 2 presynaptic proteins, SNAP25 (600322) and synapsin I (SYN1; 313440), and increased extracellular basal glutamate levels and release of glutamate evoked by high potassium. Conversely, knockdown of endogenous dysbindin protein by small interfering RNA (siRNA) resulted in reduction of presynaptic protein expression and glutamate release, suggesting that dysbindin might influence exocytotic glutamate release via upregulation of the molecules in presynaptic machinery. Overexpression of dysbindin increased phosphorylation of Akt (164730) and protected cortical neurons against neuronal death due to serum deprivation; these effects were blocked by a phosphatidylinositol 3-kinase (PI3-kinase) inhibitor. SiRNA-mediated silencing of dysbindin protein diminished Akt phosphorylation and facilitated neuronal death induced by serum deprivation, suggesting that dysbindin may promote neuronal viability through PI3-kinase-Akt signaling. </p><p>To better understand how neural function is stabilized during development and throughout life, Dickman and Davis (2009) used an electrophysiology-based forward genetic screen and assessed the function of more than 250 neuronally expressed genes for a role in the homeostatic modulation of synaptic transmission in Drosophila. This screen ruled out the involvement of numerous synaptic proteins and identified a critical function for dysbindin, a gene linked to schizophrenia in humans (see 600511). Dickman and Davis (2009) found that dysbindin is required presynaptically for the retrograde, homeostatic modulation of neurotransmission, and functions in a dose-dependent manner downstream or independently of calcium influx. Thus, Dickman and Davis (2009) concluded that dysbindin is essential for adaptive neural plasticity and may link altered homeostatic signaling with a complex neurologic disease. </p><p>Locke et al. (2009) showed that TRIM32 is a widely expressed ubiquitin ligase that is localized to the Z-line in skeletal muscle. TRIM32 bound and ubiquitinated dysbindin, augmenting its degradation. Knockdown of TRIM32 in myoblasts resulted in elevated levels of dysbindin. </p><p>Using brain samples from 28 Caucasian schizophrenia patients and 28 age- and sex-matched controls, Tang et al. (2009) reported that Western blotting of whole-tissue lysates of dorsolateral prefrontal cortex (DLPFC) revealed significant reductions in dysbindin-1C (but not in dysbindin-1A or -1B) in schizophrenia (p = 0.022). These reductions occurred without any significant change in levels of the encoding transcript in the same tissue samples and in the absence of the only DTNBP1 risk haplotype for schizophrenia reported in the United States (see Funke et al. (2004) and 600511). No significant correlations were found between case-control differences in any dysbindin-1 isoform and the case-control differences in its encoding mRNA. The mean 60% decrease in dysbindin-1C observed in 71% of the case-control pairs appeared to reflect abnormalities in mRNA translation and/or processes promoting dysbindin-1C degradation. Given the predominantly postsynaptic localization of dysbindin-1C and known postsynaptic effects of dysbindin-1 reductions in the rodent equivalent of the DLPFC, Tang et al. (2009) suggested that decreased dysbindin-1C in the DLPFC may contribute to the cognitive deficits of schizophrenia by promoting NMDA receptor hypofunction in fast-spiking interneurons. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Gross (2015) mapped the DTNBP1 gene to chromosome 6p22.3 based on an alignment of the DTNBP1 sequence (GenBank AF061734) with the genomic sequence (GRCh38).</p>
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</span>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p><strong><em>Hermansky-Pudlak Syndrome 7</em></strong></p><p>
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Li et al. (2003) screened for mutations in the 10 exons of the DTNBP1 gene in 22 unrelated non-Puerto Rican individuals with Hermansky-Pudlak syndrome (HPS) who did not have mutations in HPS1 (604982), HPS3 (606118), HPS4 (606682), HPS5 (607521), or HPS6 (607522). In a Portuguese woman with HPS7 (614076), they found homozygosity for a truncating mutation in the DTNBP1 gene (Q103X; 607145.0001). </p><p>In a 77-year-old Caucasian woman, born of consanguineous parents, with HPS7, Lowe et al. (2013) identified a homozygous truncating mutation in the DTNBP1 gene (W59X; 607145.0002). The mutation was found by autozygosity mapping with microsatellite markers followed by direct sequencing of the candidate DTNBP1 gene. </p><p>In a 6-year-old Paraguayan boy with HPS7, Bryan et al. (2017) identified homozygosity for the previously identified Q103X mutation in the DTNBP1 gene. Patient fibroblasts showed normal DTNBP1 mRNA expression but negligible dysbindin protein expression. </p><p><strong><em>Association of DTNBP1 with Schizophrenia Risk</em></strong></p><p>
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For a discussion of the relationship between variation in the DTNBP1 gene and risk of schizophrenia, see SCZD3 (600511).</p>
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</span>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>Hermansky-Pudlak syndrome (203300) is a genetically heterogeneous disorder characterized by oculocutaneous albinism, prolonged bleeding, and pulmonary fibrosis due to abnormal vesicle trafficking to lysosomes and related organelles such as melanosomes and platelet-dense granules. In mice, at least 16 loci are associated with HPS, including 'sandy' (sdy) (Swank et al., 1991). Li et al. (2003) showed that the sdy mutant mouse expresses no dysbindin protein owing to a deletion in the gene Dtnbp1. They confirmed that mutation of dysbindin causes the sdy phenotype and that dysbindin is important for normal platelet-dense granule and melanosome biogenesis. </p><p>Tang et al. (2009) found that hippocampal neurons derived from Dtnbp1-null mice had about a 50% increase in surface expression of Nr2a (138253), a subunit of the tetrameric NMDA receptor, compared to control, whereas surface expression of Nr2b (138252) was unaffected. Western blot analysis showed no difference in levels of these proteins in the adult hippocampus of mutant mice compared to wildtype. Expression of dysbindin reduced Nr2a surface expression in both wildtype and Dtnbp1-null neurons. Electrophysiologic recordings of Dtnbp1-null hippocampal slices showed an increase in NMDA receptor excitatory postsynaptic currents mediated by Nr2a as well as an increase in long-term potentiation, suggesting an alteration in synaptic plasticity in the hippocampus. Basal synaptic transmission and long-term depression were normal. The findings suggested that murine dysbindin controls hippocampal long-term potentiation by selective and direct regulation of the surface expression of Nr2a. Tang et al. (2009) noted that Nr2a undergoes postendocytic sorting through the lysosomal pathway. They suggested that knockout of dysbindin may divert endocytosed membrane proteins back to the cell surface rather than to the lysosome. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>2 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 HERMANSKY-PUDLAK SYNDROME 7</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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DTNBP1, GLN103TER ({dbSNP 104893945})
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<br />
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SNP: rs104893945,
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gnomAD: rs104893945,
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ClinVar: RCV000003601, RCV002512713
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</span>
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<div>
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<span class="mim-text-font">
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<p>In a 48-year-old Portuguese woman with Hermansky-Pudlak syndrome (HPS7; 614076), Li et al. (2003) found homozygosity for a 307C-T transition in the DTNBP1 gene resulting in the amino acid substitution gln103 to ter (Q103X) in homozygous state. Bleeding time was 13 minutes, and platelet aggregation indicated a storage-pool deficiency. The woman had mild shortness of breath on exertion and reduced lung compliance but otherwise normal pulmonary function and high resolution computed tomography (CT) chest scans, and had no muscle weakness or ataxia. Her parents were first cousins. </p><p>In a 6-year-old Paraguayan boy with HPS in whom no mutations in other genes associated with HPS were found, Bryan et al. (2017) identified homozygosity for the Q103X mutation in the DTNBP1 gene. The mutation was found by exome sequencing and confirmed by Sanger sequencing. DNA of the parents was not tested. Patient fibroblasts showed normal DTNBP1 mRNA levels but markedly reduced dysbindin protein expression. The authors noted that the Q103X mutation had a low frequency in the ExAC database, being reported in only 2 of 120,818 alleles from multiple populations. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 HERMANSKY-PUDLAK SYNDROME 7</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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DTNBP1, TRP59TER
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<br />
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SNP: rs727502866,
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gnomAD: rs727502866,
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ClinVar: RCV000150041
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a 77-year-old Caucasian woman, born of consanguineous parents, with Hermansky-Pudlak syndrome-7 (HPS7; 614076), Lowe et al. (2013) identified a homozygous c.177G-A transition in exon 4 of the DTNBP1 gene, resulting in a trp59-to-ter (W59X) substitution. The mutation was found by autozygosity mapping with microsatellite markers followed by direct sequencing of the candidate DTNBP1 gene. The patient had a lifelong bleeding tendency, pale skin and hair, and lifelong reduced visual acuity and nystagmus. She had no evidence of pulmonary disease but did have granulomatous colitis diagnosed as Crohn disease. Platelet studies showed impaired aggregation responses and a lack of dense granule secretion. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Benson, M. A., Newey, S. E., Martin-Rendon, E., Hawkes, R., Blake, D. J.
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<strong>Dysbindin, a novel coiled-coil-containing protein that interacts with the dystrobrevins in muscle and brain.</strong>
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J. Biol. Chem. 276: 24232-24241, 2001.
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[PubMed: 11316798]
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[Full Text: https://doi.org/10.1074/jbc.M010418200]
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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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Bryan, M. M., Tolman, N. J., Simon, K. L., Huizing, M., Hufnagel, R. B., Brooks, B. P., Speransky, V., Mullikin, J. C., Gahl, W. A., Malicdan, M. C. V., Gochuico, B. R.
|
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<strong>Clinical and molecular phenotyping of a child with Hermansky-Pudlak syndrome-7, an uncommon genetic type of HPS.</strong>
|
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Molec. Genet. Metab. 120: 378-383, 2017.
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[PubMed: 28259707]
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[Full Text: https://doi.org/10.1016/j.ymgme.2017.02.007]
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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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Dickman, D. K., Davis, G. W.
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<strong>The schizophrenia susceptibility gene dysbindin controls synaptic homeostasis.</strong>
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Science 326: 1127-1130, 2009.
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[PubMed: 19965435]
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[Full Text: https://doi.org/10.1126/science.1179685]
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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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Funke, B., Finn, C. T., Plocik, A. M., Lake, S., DeRosse, P., Kane, J. M., Kucherlapati, R., Malhotra, A. K.
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<strong>Association of the DTNBP1 locus with schizophrenia in a U.S. population.</strong>
|
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Am. J. Hum. Genet. 75: 891-898, 2004.
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[PubMed: 15362017]
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[Full Text: https://doi.org/10.1086/425279]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Gross, M. B.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 2/17/2015.
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Li, W., Zhang, Q., Oiso, N., Novak, E. K., Gautam, R., O'Brien, E. P., Tinsley, C. L., Blake, D. J., Spritz, R. A., Copeland, N. G., Jenkins, N. A., Amato, D., Roe, B. A., Starcevic, M., Dell'Angelica, E. C., Elliott, R. W., Mishra, V., Kingsmore, S. F., Paylor, R. E., Swank, R. T.
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<strong>Hermansky-Pudlak syndrome type 7 (HPS-7) results from mutant dysbindin, a member of the biogenesis of lysosome-related organelles complex 1 (BLOC-1).</strong>
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Nature Genet. 35: 84-89, 2003.
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[PubMed: 12923531]
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[Full Text: https://doi.org/10.1038/ng1229]
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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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Locke, M., Tinsley, C. L., Benson, M. A., Blake, D. J.
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<strong>TRIM32 is an E3 ubiquitin ligase for dysbindin.</strong>
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Hum. Molec. Genet. 18: 2344-2358, 2009.
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[PubMed: 19349376]
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[Full Text: https://doi.org/10.1093/hmg/ddp167]
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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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Lowe, G. C., Sanchez Guiu, I., Chapman, O., Rivera, J., Lordkipanidze, M., Dovlatova, N., Wilde, J., Watson, S. P., Morgan, N. V.
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<strong>Microsatellite markers as a rapid approach for autozygosity mapping in Hermansky-Pudlak syndrome: identification of the second HPS7 mutation in a patient presenting late in life. (Letter)</strong>
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Thromb. Haemost. 109: 766-768, 2013.
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[PubMed: 23364359]
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[Full Text: https://doi.org/10.1160/TH12-11-0876]
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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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Numakawa, T., Yagasaki, Y., Ishimoto, T., Okada, T., Suzuki, T., Iwata, N., Ozaki, N., Taguchi, T., Tatsumi, M., Kamijima, K., Straub, R. E., Weinberger, D. R., Kunugi, H., Hashimoto, R.
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<strong>Evidence of novel neuronal functions of dysbindin, a susceptibility gene for schizophrenia.</strong>
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Hum. Molec. Genet. 13: 2699-2708, 2004.
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[PubMed: 15345706]
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[Full Text: https://doi.org/10.1093/hmg/ddh280]
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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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Swank, R. T., Sweet, H. O., Davisson, M. T., Reddington, M., Novak, E. K.
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<strong>Sandy: a new mouse model for platelet storage pool deficiency.</strong>
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Genet. Res. 58: 51-62, 1991.
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[PubMed: 1936982]
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[Full Text: https://doi.org/10.1017/s0016672300029608]
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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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Talbot, K., Eidem, W. L., Tinsley, C. L., Benson, M. A., Thompson, E. W., Smith, R. J., Hahn, C.-G., Siegel, S. J., Trojanowski, J. Q., Gur, R. E., Blake, D. J., Arnold, S. E.
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<strong>Dysbindin-1 is reduced in intrinsic, glutamatergic terminals of the hippocampal formation in schizophrenia.</strong>
|
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J. Clin. Invest. 113: 1353-1363, 2004.
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[PubMed: 15124027]
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[Full Text: https://doi.org/10.1172/JCI20425]
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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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Tang, J., LeGros, R. P., Louneva, N., Yeh, L., Cohen, J. W., Hahn, C.-G., Blake, D. J., Arnold, S. E., Talbot, K.
|
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<strong>Dysbindin-1 in dorsolateral prefrontal cortex of schizophrenia cases is reduced in an isoform-specific manner unrelated to dysbindin-1 mRNA expression.</strong>
|
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Hum. Molec. Genet. 18: 3851-3863, 2009.
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[PubMed: 19617633]
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[Full Text: https://doi.org/10.1093/hmg/ddp329]
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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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Tang, T. T.-T., Yang, F., Chen, B.-S., Lu, Y., Ji, Y., Roche, K. W., Lu, B.
|
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<strong>Dysbindin regulates hippocampal LTP by controlling NMDA receptor surface expression.</strong>
|
|
Proc. Nat. Acad. Sci. 106: 21395-21400, 2009.
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[PubMed: 19955431]
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[Full Text: https://doi.org/10.1073/pnas.0910499106]
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</p>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<div class="row">
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Michael Muriello - updated : 02/02/2018<br>Matthew B. Gross - updated : 2/17/2015<br>Cassandra L. Kniffin - updated : 1/21/2015<br>Cassandra L. Kniffin - updated : 9/25/2013<br>George E. Tiller - updated : 8/6/2010<br>George E. Tiller - updated : 3/30/2010<br>Ada Hamosh - updated : 12/29/2009<br>George E. Tiller - updated : 11/17/2008<br>Ada Hamosh - updated : 8/19/2008<br>George E. Tiller - updated : 6/13/2007<br>Victor A. McKusick - updated : 10/10/2006<br>John Logan Black, III - updated : 7/13/2006<br>John Logan Black, III - updated : 4/6/2006<br>Victor A. McKusick - updated : 11/1/2004<br>John Logan Black, III - updated : 7/8/2004<br>Cassandra L. Kniffin - updated : 6/28/2004<br>Victor A. McKusick - updated : 12/18/2003<br>Victor A. McKusick - updated : 8/21/2003<br>Victor A. McKusick - updated : 1/22/2003<br>Victor A. McKusick - updated : 9/27/2002
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