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<title>
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Entry
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- *611203 - DNAJ/HSP40 HOMOLOG, SUBFAMILY C, MEMBER 5; DNAJC5
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- OMIM
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</nav>
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<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
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<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
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<input type="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
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<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
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Advanced Search
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/entry"> OMIM </a>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/geneMap"> Gene Map </a>
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</form>
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<p />
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<div class="row">
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*611203</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<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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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/611203">Table View</a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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</li>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000101152;t=ENST00000360864" 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=80331" 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=611203" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000101152;t=ENST00000360864" 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_025219,XM_011529048,XM_047440508,XM_047440509,XM_047440510,XM_047440511,XM_047440512" 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_025219" 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=611203" 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=08539&isoform_id=08539_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/DNAJC5" 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/10440536,15213953,18676430,31565763,45504382,50950001,119595597,119595598,119595599,158260193,193785943,768018320,2217336220,2217336222,2217336224,2217336226,2217336228,2462581599,2462581601,2462581603,2462581605,2462581607,2462581609,2462581611" 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/Q9H3Z4" 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=80331" 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=ENSG00000101152;t=ENST00000360864" 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=DNAJC5" 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=DNAJC5" 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+80331" 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/DNAJC5" 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:80331" 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/80331" 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=chr20&hgg_gene=ENST00000360864.9&hgg_start=63895126&hgg_end=63936011&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
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<span class="panel-title">
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<span class="small">
|
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://medlineplus.gov/genetics/gene/dnajc5" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=611203[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=611203[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/ENSG00000101152" 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=DNAJC5" 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=DNAJC5" 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=DNAJC5" 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=DNAJC5&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/PA27422" 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:16235" 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/FBgn0004179.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:892995" 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/DNAJC5#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:892995" 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/80331/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=80331" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00001032;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-031113-20" 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">
|
|
<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
|
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</div>
|
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</a>
|
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</span>
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</span>
|
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:80331" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=DNAJC5&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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611203
|
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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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DNAJ/HSP40 HOMOLOG, SUBFAMILY C, MEMBER 5; DNAJC5
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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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
DNAJ/HSP40 HOMOLOG, SUBFAMILY C, MEMBER 5, ALPHA; DNAJC5A<br />
|
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CYSTEINE STRING PROTEIN; CSP<br />
|
|
CSP-ALPHA
|
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</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
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<div>
|
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<br />
|
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</div>
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</div>
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<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=DNAJC5" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">DNAJC5</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>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/20/487?start=-3&limit=10&highlight=487">20q13.33</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr20:63895126-63936011&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'})">20:63,895,126-63,936,011</a> </span>
|
|
</em>
|
|
</strong>
|
|
<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>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
|
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<tr class="active">
|
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<th>
|
|
Location
|
|
</th>
|
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<th>
|
|
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>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
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Ceroid lipofuscinosis, neuronal, 4 (Kufs type), autosomal dominant
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<p>The DNAJC5 gene encodes the cysteine string protein, a presynaptic J protein expressed in neural tissues as well as in synaptic and clathrin-coated vesicles (summary by <a href="#4" class="mim-tip-reference" title="Cadieux-Dion, M., Andermann, E., Lachance-Touchette, P., Ansorge, O., Meloche, C., Barnabe, A., Kuzniecky, R. I., Andermann, F., Faught, E., Leonberg, S., Damiano, J. A., Berkovic, S. F., Rouleau, G. A., Cossette, P. <strong>Recurrent mutations in DNAJC5 cause autosomal dominant Kufs disease.</strong> Clin. Genet. 83: 571-575, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22978711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22978711</a>] [<a href="https://doi.org/10.1111/cge.12020" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22978711">Cadieux-Dion et al., 2013</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22978711" 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 antibody directed against rat Csp to screen a brain cDNA expression library, <a href="#5" class="mim-tip-reference" title="Coppola, T., Gundersen, C. <strong>Widespread expression of human cysteine string proteins.</strong> FEBS Lett. 391: 269-272, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8764987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8764987</a>] [<a href="https://doi.org/10.1016/0014-5793(96)00750-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8764987">Coppola and Gundersen (1996)</a> obtained a full-length human CSP clone. The deduced 198-amino acid protein differs from rat Csp at only 1 residue. <a href="#5" class="mim-tip-reference" title="Coppola, T., Gundersen, C. <strong>Widespread expression of human cysteine string proteins.</strong> FEBS Lett. 391: 269-272, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8764987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8764987</a>] [<a href="https://doi.org/10.1016/0014-5793(96)00750-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8764987">Coppola and Gundersen (1996)</a> also cloned a splice variant of CSP that contains a 72-nucleotide insertion that introduces an in-frame stop codon. This variant encodes a deduced 167-amino acid protein that is identical to the full-length protein for the first 164 amino acids. Northern blot analysis detected at least 3 CSP variants in all 8 human tissues examined. Western blot analysis of human blood detected CSP at an apparent molecular mass of 35 kD. Treatment with a deacylating agent caused a downward shift of 7 kD in apparent mass. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8764987" 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="#14" class="mim-tip-reference" title="Tobaben, S., Thakur, P., Fernandez-Chacon, R., Sudhof, T. C., Rettig, J., Stahl, B. <strong>A trimeric protein complex functions as a synaptic chaperone machine.</strong> Neuron 31: 987-999, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11580898/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11580898</a>] [<a href="https://doi.org/10.1016/s0896-6273(01)00427-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11580898">Tobaben et al. (2001)</a> showed that the 198-amino acid rat Csp protein contains an N-terminal J domain, followed by a cysteine string and a C-terminal domain. They noted that most of the cysteines are palmitoylated and are required for membrane targeting of Csp. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11580898" 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 real-time RT-PCR, <a href="#6" class="mim-tip-reference" title="Fernandez-Chacon, R., Wolfel, M., Nishimune, H., Tabares, L., Schmitz, F., Castellano-Munoz, M., Rosenmund, C., Montesinos, M. L., Sanes, J. R., Schneggenburger, R., Sudhof, T. C. <strong>The synaptic vesicle protein CSP-alpha prevents presynaptic degeneration.</strong> Neuron 42: 237-251, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15091340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15091340</a>] [<a href="https://doi.org/10.1016/s0896-6273(04)00190-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15091340">Fernandez-Chacon et al. (2004)</a> detected Csp-alpha in mouse brain and testis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15091340" 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="#11" class="mim-tip-reference" title="Natochin, M., Campbell, T. N., Barren, B., Miller, L. C., Hameed, S., Artemyev, N. O., Braun, J. E. A. <strong>Characterization of the G-alpha-s regulator cysteine string protein.</strong> J. Biol. Chem. 280: 30236-30241, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15972823/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15972823</a>] [<a href="https://doi.org/10.1074/jbc.M500722200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15972823">Natochin et al. (2005)</a> stated that rat Csp has 2 binding sites for G proteins, one that overlaps the J domain and binds G-alpha subunits (see GNAS, <a href="/entry/139320">139320</a>), and another between the J domain and cysteine string that binds G-beta (see GNB1, <a href="/entry/139380">139380</a>) and/or the G-alpha-beta-gamma (see GNG2, <a href="/entry/606981">606981</a>) trimer. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15972823" 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="#14" class="mim-tip-reference" title="Tobaben, S., Thakur, P., Fernandez-Chacon, R., Sudhof, T. C., Rettig, J., Stahl, B. <strong>A trimeric protein complex functions as a synaptic chaperone machine.</strong> Neuron 31: 987-999, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11580898/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11580898</a>] [<a href="https://doi.org/10.1016/s0896-6273(01)00427-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11580898">Tobaben et al. (2001)</a> showed that rat Csp interacted with Sgt (SGTA; <a href="/entry/603419">603419</a>) and Hsc70 (HSPA8; <a href="/entry/600816">600816</a>) in a complex located on the synaptic vesicle surface. The complex functioned as an ATP-dependent chaperone that reactivated a denatured substrate. Sgt overexpression in cultured rat hippocampal neurons inhibited neurotransmitter release, suggesting that the Csp/Sgt/Hsc70 complex is important for maintenance of a normal synapse. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11580898" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Miller, L. C., Swayne, L. A., Chen, L., Feng, Z.-P., Wacker, J. L., Muchowski, P. J., Zamponi, G. W., Braun, J. E. A. <strong>Cysteine string protein (CSP) inhibition of N-type calcium channels is blocked by mutant huntingtin.</strong> J. Biol. Chem. 278: 53072-53081, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14570907/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14570907</a>] [<a href="https://doi.org/10.1074/jbc.M306230200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14570907">Miller et al. (2003)</a> stated that rat Csp binds both the N-type calcium channel (see <a href="/entry/601012">601012</a>) and G protein beta-gamma subunits in vitro, and that these associations give rise to tonic G protein inhibition of the calcium channel. They showed that an N-terminal fragment of human huntingtin (HTT; <a href="/entry/613004">613004</a>) with an expanded polyglutamine tract blocked association of Csp with G proteins and eliminated Csp's tonic G protein inhibition of N-type calcium channels. In contrast, an N-terminal huntingtin fragment without an expanded polyglutamine tract did not alter association of Csp with G proteins and had no effect on channel inhibition by Csp. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14570907" 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="#11" class="mim-tip-reference" title="Natochin, M., Campbell, T. N., Barren, B., Miller, L. C., Hameed, S., Artemyev, N. O., Braun, J. E. A. <strong>Characterization of the G-alpha-s regulator cysteine string protein.</strong> J. Biol. Chem. 280: 30236-30241, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15972823/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15972823</a>] [<a href="https://doi.org/10.1074/jbc.M500722200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15972823">Natochin et al. (2005)</a> showed that rat Csp stimulated GDP/GTP exchange on G-alpha-S. Modulation of G proteins by Csp was, in turn, regulated by Hsc70 and Sgt. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15972823" 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="#7" class="mim-tip-reference" title="Gross, M. B. <strong>Personal Communication.</strong> Baltimore, Md. 4/28/2011."None>Gross (2011)</a> mapped the DNAJC5 gene to chromosome 20q13.33 based on an alignment of the DNAJC5 sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=BC053642" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">BC053642</a>) with the genomic sequence (GRCh37).</p>
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<p>In a Czech family with an autosomal dominant form of Kufs disease, ceroid neuronal lipofuscinosis-4 (CLN4; <a href="/entry/162350">162350</a>), <a href="#13" class="mim-tip-reference" title="Noskova, L., Stranecky, V., Hartmannova, H., Pristoupilova, A., Baresova, V., Ivanek, R., Hulkova, H., Jahnova, H., van der Zee, J., Staropoli, J. F., Sims, K. B., Tyynela, J., Van Broeckhoven, C., Nijssen, P. C. G., Mole, S. E., Elleder, M., Kmoch, S. <strong>Mutations in DNAJC5, encoding cysteine-string protein alpha, cause autosomal-dominant adult-onset neuronal ceroid lipofuscinosis.</strong> Am. J. Hum. Genet. 89: 241-252, 2011. Note: Erratum: Am. J. Hum. Genet. 89: 589 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21820099/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21820099</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21820099[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2011.07.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21820099">Noskova et al. (2011)</a> identified a heterozygous 3-bp deletion in the DNAJC5 gene (346_348delCTC; <a href="#0001">611203.0001</a>), resulting in deletion of leu116. The mutation was found by a combination of linkage analysis, copy-number analysis, gene-expression analysis, and exome sequencing of candidate genes. Screening of this gene in 20 additional families identified pathogenic mutations, including a novel missense mutation (L115R; <a href="#0002">611203.0002</a>), in 4. Two of the families had been reported by <a href="#9" class="mim-tip-reference" title="Josephson, S. A., Schmidt, R. E., Millsap, P., McManus, D. Q., Morris, J. C. <strong>Autosomal dominant Kufs' disease: a cause of early onset dementia.</strong> J. Neurol. Sci. 188: 51-60, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11489285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11489285</a>] [<a href="https://doi.org/10.1016/s0022-510x(01)00546-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11489285">Josephson et al. (2001)</a> and <a href="#12" class="mim-tip-reference" title="Nijssen, P. C. G., Brusse, E., Leyten, A. C. M., Martin, J. J., Teepen, J. L. J. M., Roos, R. A. C. <strong>Autosomal dominant adult neuronal ceroid lipofuscinosis: parkinsonism due to both striatal and nigral dysfunction.</strong> Mov. Disord. 17: 482-487, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12112194/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12112194</a>] [<a href="https://doi.org/10.1002/mds.10104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12112194">Nijssen et al. (2002)</a>. The patients had onset of rapidly progressive neurodegenerative disorder with onset in the third or fourth decades. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11489285+21820099+12112194" 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 patients with CLN4, <a href="#1" class="mim-tip-reference" title="Benitez, B. A., Alvarado, D., Cai, Y., Mayo, K., Chakraverty, S., Norton, J., Morris, J. C., Sands, M. S., Goate, A., Cruchaga, C. <strong>Exome-sequencing confirms DNAJC5 mutations as cause of adult neuronal ceroid-lipofuscinosis.</strong> PLoS One 6: e26741, 2011. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22073189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22073189</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22073189[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/10.1371/journal.pone.0026741" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22073189">Benitez et al. (2011)</a> and <a href="#15" class="mim-tip-reference" title="Velinov, M., Dolzhanskaya, N., Gonzalez, M., Powell, E., Konidari, I., Hulme, W., Staropoli, J. F., Xin, W., Wen, G. Y., Barone, R., Coppel, S. H., Sims, K., Brown, W. T., Zuchner, S. <strong>Mutations in the gene DNAJC5 cause autosomal dominant Kufs disease in a proportion of cases: study of the Parry family and 8 other families.</strong> PLoS One 7: e29729, 2012. Note: Electronic Article. Erratum published online.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22235333/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22235333</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22235333[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/10.1371/journal.pone.0029729" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22235333">Velinov et al. (2012)</a> found the same 2 heterozygous mutations in the DNAJC5 gene as those reported by <a href="#13" class="mim-tip-reference" title="Noskova, L., Stranecky, V., Hartmannova, H., Pristoupilova, A., Baresova, V., Ivanek, R., Hulkova, H., Jahnova, H., van der Zee, J., Staropoli, J. F., Sims, K. B., Tyynela, J., Van Broeckhoven, C., Nijssen, P. C. G., Mole, S. E., Elleder, M., Kmoch, S. <strong>Mutations in DNAJC5, encoding cysteine-string protein alpha, cause autosomal-dominant adult-onset neuronal ceroid lipofuscinosis.</strong> Am. J. Hum. Genet. 89: 241-252, 2011. Note: Erratum: Am. J. Hum. Genet. 89: 589 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21820099/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21820099</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21820099[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2011.07.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21820099">Noskova et al. (2011)</a>, thus confirming the findings. <a href="#1" class="mim-tip-reference" title="Benitez, B. A., Alvarado, D., Cai, Y., Mayo, K., Chakraverty, S., Norton, J., Morris, J. C., Sands, M. S., Goate, A., Cruchaga, C. <strong>Exome-sequencing confirms DNAJC5 mutations as cause of adult neuronal ceroid-lipofuscinosis.</strong> PLoS One 6: e26741, 2011. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22073189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22073189</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22073189[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/10.1371/journal.pone.0026741" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22073189">Benitez et al. (2011)</a> studied the family originally reported by <a href="#9" class="mim-tip-reference" title="Josephson, S. A., Schmidt, R. E., Millsap, P., McManus, D. Q., Morris, J. C. <strong>Autosomal dominant Kufs' disease: a cause of early onset dementia.</strong> J. Neurol. Sci. 188: 51-60, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11489285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11489285</a>] [<a href="https://doi.org/10.1016/s0022-510x(01)00546-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11489285">Josephson et al. (2001)</a>, and <a href="#15" class="mim-tip-reference" title="Velinov, M., Dolzhanskaya, N., Gonzalez, M., Powell, E., Konidari, I., Hulme, W., Staropoli, J. F., Xin, W., Wen, G. Y., Barone, R., Coppel, S. H., Sims, K., Brown, W. T., Zuchner, S. <strong>Mutations in the gene DNAJC5 cause autosomal dominant Kufs disease in a proportion of cases: study of the Parry family and 8 other families.</strong> PLoS One 7: e29729, 2012. Note: Electronic Article. Erratum published online.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22235333/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22235333</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22235333[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/10.1371/journal.pone.0029729" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22235333">Velinov et al. (2012)</a> studied the Parry family originally reported by <a href="#2" class="mim-tip-reference" title="Boehme, D. H., Cottrell, J. C., Leonberg, S. C., Zeman, W. <strong>A dominant form of neuronal ceroid-lipofuscinosis.</strong> Brain 94: 745-760, 1971.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5132971/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5132971</a>] [<a href="https://doi.org/10.1093/brain/94.4.745" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5132971">Boehme et al. (1971)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21820099+11489285+22235333+5132971+22073189" 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 linkage analysis combined with exome sequencing in the large family (Parry family) with adult-onset CLN reported by <a href="#2" class="mim-tip-reference" title="Boehme, D. H., Cottrell, J. C., Leonberg, S. C., Zeman, W. <strong>A dominant form of neuronal ceroid-lipofuscinosis.</strong> Brain 94: 745-760, 1971.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5132971/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5132971</a>] [<a href="https://doi.org/10.1093/brain/94.4.745" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5132971">Boehme et al. (1971)</a>, <a href="#4" class="mim-tip-reference" title="Cadieux-Dion, M., Andermann, E., Lachance-Touchette, P., Ansorge, O., Meloche, C., Barnabe, A., Kuzniecky, R. I., Andermann, F., Faught, E., Leonberg, S., Damiano, J. A., Berkovic, S. F., Rouleau, G. A., Cossette, P. <strong>Recurrent mutations in DNAJC5 cause autosomal dominant Kufs disease.</strong> Clin. Genet. 83: 571-575, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22978711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22978711</a>] [<a href="https://doi.org/10.1111/cge.12020" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22978711">Cadieux-Dion et al. (2013)</a> also identified heterozygosity for the same 3-bp deletion mutation in the DNAJC5 gene (<a href="#0001">611203.0001</a>). The mutation was confirmed by Sanger sequencing, was not found in 380 control chromosomes, and segregated with the disorder in the family. The American patient reported by <a href="#13" class="mim-tip-reference" title="Noskova, L., Stranecky, V., Hartmannova, H., Pristoupilova, A., Baresova, V., Ivanek, R., Hulkova, H., Jahnova, H., van der Zee, J., Staropoli, J. F., Sims, K. B., Tyynela, J., Van Broeckhoven, C., Nijssen, P. C. G., Mole, S. E., Elleder, M., Kmoch, S. <strong>Mutations in DNAJC5, encoding cysteine-string protein alpha, cause autosomal-dominant adult-onset neuronal ceroid lipofuscinosis.</strong> Am. J. Hum. Genet. 89: 241-252, 2011. Note: Erratum: Am. J. Hum. Genet. 89: 589 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21820099/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21820099</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21820099[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2011.07.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21820099">Noskova et al. (2011)</a> who carried this mutation was found to be from the Parry family. <a href="#4" class="mim-tip-reference" title="Cadieux-Dion, M., Andermann, E., Lachance-Touchette, P., Ansorge, O., Meloche, C., Barnabe, A., Kuzniecky, R. I., Andermann, F., Faught, E., Leonberg, S., Damiano, J. A., Berkovic, S. F., Rouleau, G. A., Cossette, P. <strong>Recurrent mutations in DNAJC5 cause autosomal dominant Kufs disease.</strong> Clin. Genet. 83: 571-575, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22978711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22978711</a>] [<a href="https://doi.org/10.1111/cge.12020" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22978711">Cadieux-Dion et al. (2013)</a> also identified the leu116del mutation in affected members of a family from Alabama reported by <a href="#3" class="mim-tip-reference" title="Burneo, J. G., Arnold, T., Palmer, C. A., Kuzniecky, R. I., Oh, S. J., Faught, E. <strong>Adult-onset neuronal ceroid lipofuscinosis (Kufs disease) with autosomal dominant inheritance in Alabama.</strong> Epilepsia 44: 841-846, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12790899/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12790899</a>] [<a href="https://doi.org/10.1046/j.1528-1157.2003.39802.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12790899">Burneo et al. (2003)</a>. Haplotype analysis did not show a founder effect between the 2 families, suggesting that it is a recurrent mutation. <a href="#4" class="mim-tip-reference" title="Cadieux-Dion, M., Andermann, E., Lachance-Touchette, P., Ansorge, O., Meloche, C., Barnabe, A., Kuzniecky, R. I., Andermann, F., Faught, E., Leonberg, S., Damiano, J. A., Berkovic, S. F., Rouleau, G. A., Cossette, P. <strong>Recurrent mutations in DNAJC5 cause autosomal dominant Kufs disease.</strong> Clin. Genet. 83: 571-575, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22978711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22978711</a>] [<a href="https://doi.org/10.1111/cge.12020" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22978711">Cadieux-Dion et al. (2013)</a> also identified a heterozygous L115R mutation in the DNAJC5 gene (<a href="#0002">611203.0002</a>) in 1 of 6 additional patients with the disorder; this patient had no family history. Overall, DNAJC5 mutations accounted for 38% of cases with unexplained adult-onset NCL in their cohort, with the mutations occurring at mutational hotspots. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5132971+21820099+22978711+12790899" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 Canadian sibs with CLN4, <a href="#8" class="mim-tip-reference" title="Jedlickova, I., Cadieux-Dion, M., Pristoupilova, A., Stranecky, V., Hartmannova, H., Hodanova, K., Baresova, V., Hulkova, H., Sikora, J., Noskova, L., Musalkova, D., Vyletal, P., Sovova, J., Cossette, P., Andermann, E., Andermann, F., Kmoch, S., Adult NCL Gene Discovery Consortium. <strong>Autosomal-dominant adult neuronal ceroid lipofuscinosis caused by duplication in DNAJC5 initially missed by Sanger and whole-exome sequencing.</strong> Europ. J. Hum. Genet. 28: 783-789, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31919451/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31919451</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31919451[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/s41431-019-0567-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31919451">Jedlickova et al. (2020)</a> identified a heterozygous 30-bp duplication in the DNAJC5 gene (c.370_399dup; <a href="#0003">611203.0003</a>), resulting in an in-frame duplication involving the central core motif of the cysteine-string domain of the CSP-alpha protein. On initial targeted Sanger sequencing of the DNAJC5 gene, the 30-bp duplication was not identified, likely due to preferential amplification of the wildtype allele and allelic drop out of the mutated allele. Furthermore, the 30-bp duplication was initially missed on whole-exome sequencing and was identified only after exome reanalysis was performed with altered variant detection thresholds. Redesign of Sanger sequencing parameters confirmed the presence of the 30-bp duplication mutant. Expression of the mutant protein in CAD5 cells demonstrated abnormal cellular localization, abnormal palmitoylation, and formation of high molecular weight aggregates. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31919451" 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="#6" class="mim-tip-reference" title="Fernandez-Chacon, R., Wolfel, M., Nishimune, H., Tabares, L., Schmitz, F., Castellano-Munoz, M., Rosenmund, C., Montesinos, M. L., Sanes, J. R., Schneggenburger, R., Sudhof, T. C. <strong>The synaptic vesicle protein CSP-alpha prevents presynaptic degeneration.</strong> Neuron 42: 237-251, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15091340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15091340</a>] [<a href="https://doi.org/10.1016/s0896-6273(04)00190-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15091340">Fernandez-Chacon et al. (2004)</a> found that Csp-alpha -/- mice appeared normal at birth but developed a progressive lethal phenotype that manifested as muscle weakness and a sensorimotor disorder at 2 to 4 weeks of age. Analysis of synaptic transmission in Csp-alpha -/- neuromuscular junctions and at the Calyx of Held synapse revealed normal Ca(2+) channel function and Ca(2+)-dependent exocytosis. However, synapses showed progressively worsening presynaptic degeneration, with persistent vacuoles, proliferation of multilamellar bodies, and protrusion of Schwann cell fingers into the neuromuscular nerve terminal. <a href="#5" class="mim-tip-reference" title="Coppola, T., Gundersen, C. <strong>Widespread expression of human cysteine string proteins.</strong> FEBS Lett. 391: 269-272, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8764987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8764987</a>] [<a href="https://doi.org/10.1016/0014-5793(96)00750-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8764987">Coppola and Gundersen (1996)</a> concluded that the degeneration of Csp-alpha -/- synapses appeared to occur in a use-dependent manner and that CSP-alpha is required to maintain the integrity of synapses in the face of use-dependent stress. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8764987+15091340" 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">rs587776892 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776892;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs587776892" 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=rs587776892" 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=RCV000023878 OR RCV000632720" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023878, RCV000632720" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023878...</a>
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<p>In affected members of a Czech family with an autosomal dominant form of Kufs disease, neuronal ceroid lipofuscinosis-4 (CLN4; <a href="/entry/162350">162350</a>), <a href="#13" class="mim-tip-reference" title="Noskova, L., Stranecky, V., Hartmannova, H., Pristoupilova, A., Baresova, V., Ivanek, R., Hulkova, H., Jahnova, H., van der Zee, J., Staropoli, J. F., Sims, K. B., Tyynela, J., Van Broeckhoven, C., Nijssen, P. C. G., Mole, S. E., Elleder, M., Kmoch, S. <strong>Mutations in DNAJC5, encoding cysteine-string protein alpha, cause autosomal-dominant adult-onset neuronal ceroid lipofuscinosis.</strong> Am. J. Hum. Genet. 89: 241-252, 2011. Note: Erratum: Am. J. Hum. Genet. 89: 589 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21820099/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21820099</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21820099[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2011.07.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21820099">Noskova et al. (2011)</a> identified a heterozygous 3-bp deletion (346_348delCTC) in the DNAJC5 gene, resulting in a deletion of leu116 (Leu116del) in a conserved region of the cysteine-string domain of the protein. Screening of this gene in 20 additional families identified this mutation in 1 affected American patient who had a family history of the disorder. The patients had onset of rapidly progressive neurodegenerative disorder with onset in the third or fourth decades. Haplotype analysis did not suggest a common origin. The mutation was not found in 200 controls. In vitro functional expression in CAD5 neuronal cells showed that the mutant protein had abnormal diffuse intracellular localization and abnormal colocalization with markers for the endoplasmic reticulum and Golgi apparatus. Immunoblot analysis indicated that the mutant protein was less efficiently palmitoylated compared to wildtype. Analysis of brain tissue from affected individuals showed significantly reduced immunostaining for DNAJC5 in the cerebral cortex compared to controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21820099" 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="#1" class="mim-tip-reference" title="Benitez, B. A., Alvarado, D., Cai, Y., Mayo, K., Chakraverty, S., Norton, J., Morris, J. C., Sands, M. S., Goate, A., Cruchaga, C. <strong>Exome-sequencing confirms DNAJC5 mutations as cause of adult neuronal ceroid-lipofuscinosis.</strong> PLoS One 6: e26741, 2011. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22073189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22073189</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22073189[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/10.1371/journal.pone.0026741" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22073189">Benitez et al. (2011)</a> identified the heterozygous 346_348delCTC mutation in affected members of a family with CLN4. The mutation, which was found by Sanger sequencing, was not present in the dbSNP (build 134) or 1000 Genomes Project databases or in more than 3,200 control chromosomes. These findings confirmed the report of <a href="#13" class="mim-tip-reference" title="Noskova, L., Stranecky, V., Hartmannova, H., Pristoupilova, A., Baresova, V., Ivanek, R., Hulkova, H., Jahnova, H., van der Zee, J., Staropoli, J. F., Sims, K. B., Tyynela, J., Van Broeckhoven, C., Nijssen, P. C. G., Mole, S. E., Elleder, M., Kmoch, S. <strong>Mutations in DNAJC5, encoding cysteine-string protein alpha, cause autosomal-dominant adult-onset neuronal ceroid lipofuscinosis.</strong> Am. J. Hum. Genet. 89: 241-252, 2011. Note: Erratum: Am. J. Hum. Genet. 89: 589 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21820099/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21820099</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21820099[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2011.07.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21820099">Noskova et al. (2011)</a>. Molecular modeling studies predicted that the mutation may weaken membrane binding by decreasing affinity of the protein for the membrane. Other functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=22073189+21820099" 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="#15" class="mim-tip-reference" title="Velinov, M., Dolzhanskaya, N., Gonzalez, M., Powell, E., Konidari, I., Hulme, W., Staropoli, J. F., Xin, W., Wen, G. Y., Barone, R., Coppel, S. H., Sims, K., Brown, W. T., Zuchner, S. <strong>Mutations in the gene DNAJC5 cause autosomal dominant Kufs disease in a proportion of cases: study of the Parry family and 8 other families.</strong> PLoS One 7: e29729, 2012. Note: Electronic Article. Erratum published online.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22235333/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22235333</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22235333[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/10.1371/journal.pone.0029729" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22235333">Velinov et al. (2012)</a> identified the 3-bp deletion mutation in affected members of the original Parry family with CLN4 (<a href="#2" class="mim-tip-reference" title="Boehme, D. H., Cottrell, J. C., Leonberg, S. C., Zeman, W. <strong>A dominant form of neuronal ceroid-lipofuscinosis.</strong> Brain 94: 745-760, 1971.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5132971/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5132971</a>] [<a href="https://doi.org/10.1093/brain/94.4.745" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5132971">Boehme et al., 1971</a>). Affected individuals also carried a heterozygous 1430A-G transition in the PRPF6 gene (<a href="/entry/613979">613979</a>), resulting in an asn477-to-ser (N477S) substitution at a highly conserved residue. The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Neither mutation was found in 2,100 control individuals. Both changes occurred within about 75 kb on chromosome 20 and were likely linked on a rare haplotype. <a href="#15" class="mim-tip-reference" title="Velinov, M., Dolzhanskaya, N., Gonzalez, M., Powell, E., Konidari, I., Hulme, W., Staropoli, J. F., Xin, W., Wen, G. Y., Barone, R., Coppel, S. H., Sims, K., Brown, W. T., Zuchner, S. <strong>Mutations in the gene DNAJC5 cause autosomal dominant Kufs disease in a proportion of cases: study of the Parry family and 8 other families.</strong> PLoS One 7: e29729, 2012. Note: Electronic Article. Erratum published online.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22235333/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22235333</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22235333[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/10.1371/journal.pone.0029729" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22235333">Velinov et al. (2012)</a> noted that a PRPF6 mutation has been associated with retinitis pigmentosa-60 (RP60; <a href="/entry/613983">613983</a>) and that some members of the Parry family had unspecified visual problems, suggesting that it may be a phenotypic modifier in this family. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5132971+22235333" 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 linkage analysis combined with exome sequencing in the large family (Parry family) with adult-onset CLN reported by <a href="#2" class="mim-tip-reference" title="Boehme, D. H., Cottrell, J. C., Leonberg, S. C., Zeman, W. <strong>A dominant form of neuronal ceroid-lipofuscinosis.</strong> Brain 94: 745-760, 1971.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5132971/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5132971</a>] [<a href="https://doi.org/10.1093/brain/94.4.745" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5132971">Boehme et al. (1971)</a>, <a href="#4" class="mim-tip-reference" title="Cadieux-Dion, M., Andermann, E., Lachance-Touchette, P., Ansorge, O., Meloche, C., Barnabe, A., Kuzniecky, R. I., Andermann, F., Faught, E., Leonberg, S., Damiano, J. A., Berkovic, S. F., Rouleau, G. A., Cossette, P. <strong>Recurrent mutations in DNAJC5 cause autosomal dominant Kufs disease.</strong> Clin. Genet. 83: 571-575, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22978711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22978711</a>] [<a href="https://doi.org/10.1111/cge.12020" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22978711">Cadieux-Dion et al. (2013)</a> identified a heterozygous 346_348del mutation. The mutation was confirmed by Sanger sequencing, was not found in 380 control chromosomes, and segregated with the disorder in the family. The American patient reported by <a href="#13" class="mim-tip-reference" title="Noskova, L., Stranecky, V., Hartmannova, H., Pristoupilova, A., Baresova, V., Ivanek, R., Hulkova, H., Jahnova, H., van der Zee, J., Staropoli, J. F., Sims, K. B., Tyynela, J., Van Broeckhoven, C., Nijssen, P. C. G., Mole, S. E., Elleder, M., Kmoch, S. <strong>Mutations in DNAJC5, encoding cysteine-string protein alpha, cause autosomal-dominant adult-onset neuronal ceroid lipofuscinosis.</strong> Am. J. Hum. Genet. 89: 241-252, 2011. Note: Erratum: Am. J. Hum. Genet. 89: 589 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21820099/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21820099</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21820099[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2011.07.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21820099">Noskova et al. (2011)</a> who carried this mutation was found to be from the Parry family. <a href="#4" class="mim-tip-reference" title="Cadieux-Dion, M., Andermann, E., Lachance-Touchette, P., Ansorge, O., Meloche, C., Barnabe, A., Kuzniecky, R. I., Andermann, F., Faught, E., Leonberg, S., Damiano, J. A., Berkovic, S. F., Rouleau, G. A., Cossette, P. <strong>Recurrent mutations in DNAJC5 cause autosomal dominant Kufs disease.</strong> Clin. Genet. 83: 571-575, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22978711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22978711</a>] [<a href="https://doi.org/10.1111/cge.12020" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22978711">Cadieux-Dion et al. (2013)</a> also identified the leu116del mutation in affected members of a family from Alabama reported by <a href="#3" class="mim-tip-reference" title="Burneo, J. G., Arnold, T., Palmer, C. A., Kuzniecky, R. I., Oh, S. J., Faught, E. <strong>Adult-onset neuronal ceroid lipofuscinosis (Kufs disease) with autosomal dominant inheritance in Alabama.</strong> Epilepsia 44: 841-846, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12790899/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12790899</a>] [<a href="https://doi.org/10.1046/j.1528-1157.2003.39802.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12790899">Burneo et al. (2003)</a>, even though the mutation in this family had not been found by <a href="#13" class="mim-tip-reference" title="Noskova, L., Stranecky, V., Hartmannova, H., Pristoupilova, A., Baresova, V., Ivanek, R., Hulkova, H., Jahnova, H., van der Zee, J., Staropoli, J. F., Sims, K. B., Tyynela, J., Van Broeckhoven, C., Nijssen, P. C. G., Mole, S. E., Elleder, M., Kmoch, S. <strong>Mutations in DNAJC5, encoding cysteine-string protein alpha, cause autosomal-dominant adult-onset neuronal ceroid lipofuscinosis.</strong> Am. J. Hum. Genet. 89: 241-252, 2011. Note: Erratum: Am. J. Hum. Genet. 89: 589 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21820099/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21820099</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21820099[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2011.07.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21820099">Noskova et al. (2011)</a>. Haplotype analysis did not show a founder effect between the 2 families, suggesting that it is a recurrent mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5132971+21820099+22978711+12790899" 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> rs387907043 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387907043;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/rs387907043?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=rs387907043" 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=rs387907043" 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=RCV000023879 OR RCV002466414" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023879, RCV002466414" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023879...</a>
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<p>In affected members of 2 unrelated families and 1 patient with autosomal dominant Kufs disease (CLN4; <a href="/entry/162350">162350</a>), <a href="#13" class="mim-tip-reference" title="Noskova, L., Stranecky, V., Hartmannova, H., Pristoupilova, A., Baresova, V., Ivanek, R., Hulkova, H., Jahnova, H., van der Zee, J., Staropoli, J. F., Sims, K. B., Tyynela, J., Van Broeckhoven, C., Nijssen, P. C. G., Mole, S. E., Elleder, M., Kmoch, S. <strong>Mutations in DNAJC5, encoding cysteine-string protein alpha, cause autosomal-dominant adult-onset neuronal ceroid lipofuscinosis.</strong> Am. J. Hum. Genet. 89: 241-252, 2011. Note: Erratum: Am. J. Hum. Genet. 89: 589 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21820099/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21820099</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21820099[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2011.07.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21820099">Noskova et al. (2011)</a> identified a heterozygous 344T-G transversion in the DNAJC5 gene, resulting in a leu115-to-arg (L115R) substitution in a conserved residue in the cysteine-string domain of the protein. Two of the families had been reported by <a href="#9" class="mim-tip-reference" title="Josephson, S. A., Schmidt, R. E., Millsap, P., McManus, D. Q., Morris, J. C. <strong>Autosomal dominant Kufs' disease: a cause of early onset dementia.</strong> J. Neurol. Sci. 188: 51-60, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11489285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11489285</a>] [<a href="https://doi.org/10.1016/s0022-510x(01)00546-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11489285">Josephson et al. (2001)</a> and <a href="#12" class="mim-tip-reference" title="Nijssen, P. C. G., Brusse, E., Leyten, A. C. M., Martin, J. J., Teepen, J. L. J. M., Roos, R. A. C. <strong>Autosomal dominant adult neuronal ceroid lipofuscinosis: parkinsonism due to both striatal and nigral dysfunction.</strong> Mov. Disord. 17: 482-487, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12112194/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12112194</a>] [<a href="https://doi.org/10.1002/mds.10104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12112194">Nijssen et al. (2002)</a>. The mutation was not found in 200 controls. Haplotype analysis did not suggest a common origin. In vitro functional expression in CAD5 neuronal cells showed that the mutant protein had abnormal diffuse intracellular localization and abnormal colocalization with markers for the endoplasmic reticulum and Golgi apparatus. Immunoblot analysis indicated that the mutant protein was less efficiently palmitoylated compared to wildtype. Analysis of brain tissue from affected individuals showed absence of immunostaining for DNAJC5 in synaptic regions in both the cerebral and cerebellar cortex compared to controls. However, there was some evidence for an insoluble DNAJC5-containing aggregate in brain lysate. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11489285+21820099+12112194" 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="#1" class="mim-tip-reference" title="Benitez, B. A., Alvarado, D., Cai, Y., Mayo, K., Chakraverty, S., Norton, J., Morris, J. C., Sands, M. S., Goate, A., Cruchaga, C. <strong>Exome-sequencing confirms DNAJC5 mutations as cause of adult neuronal ceroid-lipofuscinosis.</strong> PLoS One 6: e26741, 2011. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22073189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22073189</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22073189[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/10.1371/journal.pone.0026741" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22073189">Benitez et al. (2011)</a> identified a heterozygous L115R mutation in affected members of a large family with CLN4 originally reported by <a href="#9" class="mim-tip-reference" title="Josephson, S. A., Schmidt, R. E., Millsap, P., McManus, D. Q., Morris, J. C. <strong>Autosomal dominant Kufs' disease: a cause of early onset dementia.</strong> J. Neurol. Sci. 188: 51-60, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11489285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11489285</a>] [<a href="https://doi.org/10.1016/s0022-510x(01)00546-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11489285">Josephson et al. (2001)</a>. The mutation, which was found by whole-exome sequencing and filtered against the dbSNP (build 130) and 1000 Genomes Project databases as well as 59 in-house exomes, was confirmed by Sanger sequencing to segregate with the disorder in the family. It was also absent in an additional 1,600 controls. Molecular modeling studies predicted that the mutation may weaken membrane binding by decreasing affinity of the protein for the membrane. Other functional studies were not performed. These findings confirmed the report of <a href="#13" class="mim-tip-reference" title="Noskova, L., Stranecky, V., Hartmannova, H., Pristoupilova, A., Baresova, V., Ivanek, R., Hulkova, H., Jahnova, H., van der Zee, J., Staropoli, J. F., Sims, K. B., Tyynela, J., Van Broeckhoven, C., Nijssen, P. C. G., Mole, S. E., Elleder, M., Kmoch, S. <strong>Mutations in DNAJC5, encoding cysteine-string protein alpha, cause autosomal-dominant adult-onset neuronal ceroid lipofuscinosis.</strong> Am. J. Hum. Genet. 89: 241-252, 2011. Note: Erratum: Am. J. Hum. Genet. 89: 589 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21820099/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21820099</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21820099[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2011.07.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21820099">Noskova et al. (2011)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11489285+22073189+21820099" 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="#15" class="mim-tip-reference" title="Velinov, M., Dolzhanskaya, N., Gonzalez, M., Powell, E., Konidari, I., Hulme, W., Staropoli, J. F., Xin, W., Wen, G. Y., Barone, R., Coppel, S. H., Sims, K., Brown, W. T., Zuchner, S. <strong>Mutations in the gene DNAJC5 cause autosomal dominant Kufs disease in a proportion of cases: study of the Parry family and 8 other families.</strong> PLoS One 7: e29729, 2012. Note: Electronic Article. Erratum published online.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22235333/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22235333</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22235333[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/10.1371/journal.pone.0029729" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22235333">Velinov et al. (2012)</a> identified a heterozygous L115R mutation in a patient with CLN4B. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22235333" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Cadieux-Dion, M., Andermann, E., Lachance-Touchette, P., Ansorge, O., Meloche, C., Barnabe, A., Kuzniecky, R. I., Andermann, F., Faught, E., Leonberg, S., Damiano, J. A., Berkovic, S. F., Rouleau, G. A., Cossette, P. <strong>Recurrent mutations in DNAJC5 cause autosomal dominant Kufs disease.</strong> Clin. Genet. 83: 571-575, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22978711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22978711</a>] [<a href="https://doi.org/10.1111/cge.12020" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22978711">Cadieux-Dion et al. (2013)</a> identified a heterozygous L115R mutation in a patient with sporadic occurrence of CLN4B. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22978711" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 CEROID LIPOFUSCINOSIS, NEURONAL, 4 (KUFS TYPE)</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">rs1600887859 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1600887859;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1600887859" 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=rs1600887859" 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=RCV000850191" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000850191" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000850191</a>
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<p>In 2 sibs with autosomal dominant Kufs disease (CLN4; <a href="/entry/162350">162350</a>), <a href="#8" class="mim-tip-reference" title="Jedlickova, I., Cadieux-Dion, M., Pristoupilova, A., Stranecky, V., Hartmannova, H., Hodanova, K., Baresova, V., Hulkova, H., Sikora, J., Noskova, L., Musalkova, D., Vyletal, P., Sovova, J., Cossette, P., Andermann, E., Andermann, F., Kmoch, S., Adult NCL Gene Discovery Consortium. <strong>Autosomal-dominant adult neuronal ceroid lipofuscinosis caused by duplication in DNAJC5 initially missed by Sanger and whole-exome sequencing.</strong> Europ. J. Hum. Genet. 28: 783-789, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31919451/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31919451</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31919451[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/s41431-019-0567-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31919451">Jedlickova et al. (2020)</a> identified a heterozygous 30-bp duplication (c.370_399dup, NM_025219.2) in exon 4 of the DNAJC5 gene, resulting in an in-frame duplication (Cys124_Cys133). The mutation was identified by whole-exome sequencing and confirmed by Sanger sequencing. The duplication encodes the central core motif of the cysteine-string domain of CSP-alpha. Expression of mutant CSP-alpha in CAD5 cells showed abnormal cellular localization with reduced expression in the plasma membrane, abnormal palmitoylation with only the nonpalmitoylated form present, and formation of high molecular weight aggregates. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31919451" 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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Benitez, B. A., Alvarado, D., Cai, Y., Mayo, K., Chakraverty, S., Norton, J., Morris, J. C., Sands, M. S., Goate, A., Cruchaga, C.
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<strong>Exome-sequencing confirms DNAJC5 mutations as cause of adult neuronal ceroid-lipofuscinosis.</strong>
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PLoS One 6: e26741, 2011. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22073189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22073189</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22073189[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=22073189" 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/10.1371/journal.pone.0026741" target="_blank">Full Text</a>]
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Boehme, D. H., Cottrell, J. C., Leonberg, S. C., Zeman, W.
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<strong>A dominant form of neuronal ceroid-lipofuscinosis.</strong>
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Brain 94: 745-760, 1971.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5132971/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5132971</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5132971" 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/brain/94.4.745" target="_blank">Full Text</a>]
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Burneo, J. G., Arnold, T., Palmer, C. A., Kuzniecky, R. I., Oh, S. J., Faught, E.
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<strong>Adult-onset neuronal ceroid lipofuscinosis (Kufs disease) with autosomal dominant inheritance in Alabama.</strong>
|
|
Epilepsia 44: 841-846, 2003.
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12790899/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12790899</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12790899" 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/10.1046/j.1528-1157.2003.39802.x" target="_blank">Full Text</a>]
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Cadieux-Dion, M., Andermann, E., Lachance-Touchette, P., Ansorge, O., Meloche, C., Barnabe, A., Kuzniecky, R. I., Andermann, F., Faught, E., Leonberg, S., Damiano, J. A., Berkovic, S. F., Rouleau, G. A., Cossette, P.
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<strong>Recurrent mutations in DNAJC5 cause autosomal dominant Kufs disease.</strong>
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Clin. Genet. 83: 571-575, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22978711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22978711</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22978711" 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/10.1111/cge.12020" target="_blank">Full Text</a>]
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Coppola, T., Gundersen, C.
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<strong>Widespread expression of human cysteine string proteins.</strong>
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FEBS Lett. 391: 269-272, 1996.
|
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|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8764987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8764987</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8764987" 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/10.1016/0014-5793(96)00750-8" target="_blank">Full Text</a>]
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Fernandez-Chacon, R., Wolfel, M., Nishimune, H., Tabares, L., Schmitz, F., Castellano-Munoz, M., Rosenmund, C., Montesinos, M. L., Sanes, J. R., Schneggenburger, R., Sudhof, T. C.
|
|
<strong>The synaptic vesicle protein CSP-alpha prevents presynaptic degeneration.</strong>
|
|
Neuron 42: 237-251, 2004.
|
|
|
|
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|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15091340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15091340</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15091340" 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/s0896-6273(04)00190-4" target="_blank">Full Text</a>]
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<a id="Gross2011" class="mim-anchor"></a>
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Gross, M. B.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 4/28/2011.
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</p>
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<li>
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<a id="8" class="mim-anchor"></a>
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<a id="Jedlickova2020" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Jedlickova, I., Cadieux-Dion, M., Pristoupilova, A., Stranecky, V., Hartmannova, H., Hodanova, K., Baresova, V., Hulkova, H., Sikora, J., Noskova, L., Musalkova, D., Vyletal, P., Sovova, J., Cossette, P., Andermann, E., Andermann, F., Kmoch, S., Adult NCL Gene Discovery Consortium.
|
|
<strong>Autosomal-dominant adult neuronal ceroid lipofuscinosis caused by duplication in DNAJC5 initially missed by Sanger and whole-exome sequencing.</strong>
|
|
Europ. J. Hum. Genet. 28: 783-789, 2020.
|
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|
|
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31919451/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31919451</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31919451[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=31919451" 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/s41431-019-0567-2" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="9" class="mim-anchor"></a>
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<a id="Josephson2001" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Josephson, S. A., Schmidt, R. E., Millsap, P., McManus, D. Q., Morris, J. C.
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|
<strong>Autosomal dominant Kufs' disease: a cause of early onset dementia.</strong>
|
|
J. Neurol. Sci. 188: 51-60, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11489285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11489285</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11489285" 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/s0022-510x(01)00546-9" 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="Miller2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Miller, L. C., Swayne, L. A., Chen, L., Feng, Z.-P., Wacker, J. L., Muchowski, P. J., Zamponi, G. W., Braun, J. E. A.
|
|
<strong>Cysteine string protein (CSP) inhibition of N-type calcium channels is blocked by mutant huntingtin.</strong>
|
|
J. Biol. Chem. 278: 53072-53081, 2003.
|
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|
|
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14570907/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14570907</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14570907" 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.M306230200" target="_blank">Full Text</a>]
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<li>
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<a id="11" class="mim-anchor"></a>
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<a id="Natochin2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Natochin, M., Campbell, T. N., Barren, B., Miller, L. C., Hameed, S., Artemyev, N. O., Braun, J. E. A.
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<strong>Characterization of the G-alpha-s regulator cysteine string protein.</strong>
|
|
J. Biol. Chem. 280: 30236-30241, 2005.
|
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|
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15972823/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15972823</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15972823" 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.M500722200" target="_blank">Full Text</a>]
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<a id="12" class="mim-anchor"></a>
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<a id="Nijssen2002" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Nijssen, P. C. G., Brusse, E., Leyten, A. C. M., Martin, J. J., Teepen, J. L. J. M., Roos, R. A. C.
|
|
<strong>Autosomal dominant adult neuronal ceroid lipofuscinosis: parkinsonism due to both striatal and nigral dysfunction.</strong>
|
|
Mov. Disord. 17: 482-487, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12112194/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12112194</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12112194" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/mds.10104" 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="Noskova2011" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Noskova, L., Stranecky, V., Hartmannova, H., Pristoupilova, A., Baresova, V., Ivanek, R., Hulkova, H., Jahnova, H., van der Zee, J., Staropoli, J. F., Sims, K. B., Tyynela, J., Van Broeckhoven, C., Nijssen, P. C. G., Mole, S. E., Elleder, M., Kmoch, S.
|
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<strong>Mutations in DNAJC5, encoding cysteine-string protein alpha, cause autosomal-dominant adult-onset neuronal ceroid lipofuscinosis.</strong>
|
|
Am. J. Hum. Genet. 89: 241-252, 2011. Note: Erratum: Am. J. Hum. Genet. 89: 589 only, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21820099/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21820099</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21820099[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=21820099" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ajhg.2011.07.003" 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="14" class="mim-anchor"></a>
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<a id="Tobaben2001" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tobaben, S., Thakur, P., Fernandez-Chacon, R., Sudhof, T. C., Rettig, J., Stahl, B.
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<strong>A trimeric protein complex functions as a synaptic chaperone machine.</strong>
|
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Neuron 31: 987-999, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11580898/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11580898</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11580898" 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/s0896-6273(01)00427-5" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="15" class="mim-anchor"></a>
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<a id="Velinov2012" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Velinov, M., Dolzhanskaya, N., Gonzalez, M., Powell, E., Konidari, I., Hulme, W., Staropoli, J. F., Xin, W., Wen, G. Y., Barone, R., Coppel, S. H., Sims, K., Brown, W. T., Zuchner, S.
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<strong>Mutations in the gene DNAJC5 cause autosomal dominant Kufs disease in a proportion of cases: study of the Parry family and 8 other families.</strong>
|
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PLoS One 7: e29729, 2012. Note: Electronic Article. Erratum published online.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22235333/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22235333</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22235333[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=22235333" 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/10.1371/journal.pone.0029729" target="_blank">Full Text</a>]
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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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<a id="contributors" 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="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Hilary J. Vernon - updated : 09/02/2022
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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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Cassandra L. Kniffin - updated : 6/30/2014<br>Cassandra L. Kniffin - updated : 6/3/2013<br>Cassandra L. Kniffin - updated : 9/15/2011<br>Matthew B. Gross - updated : 4/28/2011<br>Patricia A. Hartz - updated : 4/19/2011
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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="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 : 7/16/2007
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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="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 09/02/2022
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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 : 12/01/2021<br>carol : 07/27/2021<br>carol : 07/26/2021<br>carol : 05/02/2017<br>joanna : 06/29/2016<br>carol : 1/29/2015<br>carol : 1/29/2015<br>alopez : 7/2/2014<br>mcolton : 7/1/2014<br>ckniffin : 6/30/2014<br>carol : 6/7/2013<br>ckniffin : 6/3/2013<br>carol : 10/21/2011<br>carol : 9/16/2011<br>ckniffin : 9/15/2011<br>mgross : 4/28/2011<br>mgross : 4/28/2011<br>terry : 4/19/2011<br>wwang : 9/15/2009<br>carol : 8/17/2007<br>mgross : 7/16/2007
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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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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 611203
|
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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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DNAJ/HSP40 HOMOLOG, SUBFAMILY C, MEMBER 5; DNAJC5
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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DNAJ/HSP40 HOMOLOG, SUBFAMILY C, MEMBER 5, ALPHA; DNAJC5A<br />
|
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CYSTEINE STRING PROTEIN; CSP<br />
|
|
CSP-ALPHA
|
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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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<p>
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<span class="mim-text-font">
|
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<strong><em>HGNC Approved Gene Symbol: DNAJC5</em></strong>
|
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
|
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<strong>
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<em>
|
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Cytogenetic location: 20q13.33
|
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Genomic coordinates <span class="small">(GRCh38)</span> : 20:63,895,126-63,936,011 </span>
|
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</em>
|
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</strong>
|
|
<span class="small">(from NCBI)</span>
|
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</h4>
|
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<div>
|
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<table class="table table-bordered table-condensed small mim-table-padding">
|
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<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
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</th>
|
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<th>
|
|
Phenotype
|
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</th>
|
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<th>
|
|
Phenotype <br /> MIM number
|
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</th>
|
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<th>
|
|
Inheritance
|
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</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
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</tr>
|
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</thead>
|
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<tbody>
|
|
|
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<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
20q13.33
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Ceroid lipofuscinosis, neuronal, 4 (Kufs type), autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
162350
|
|
</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
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</h4>
|
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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 DNAJC5 gene encodes the cysteine string protein, a presynaptic J protein expressed in neural tissues as well as in synaptic and clathrin-coated vesicles (summary by Cadieux-Dion et al., 2013). </p>
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</span>
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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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<span class="mim-text-font">
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<p>Using antibody directed against rat Csp to screen a brain cDNA expression library, Coppola and Gundersen (1996) obtained a full-length human CSP clone. The deduced 198-amino acid protein differs from rat Csp at only 1 residue. Coppola and Gundersen (1996) also cloned a splice variant of CSP that contains a 72-nucleotide insertion that introduces an in-frame stop codon. This variant encodes a deduced 167-amino acid protein that is identical to the full-length protein for the first 164 amino acids. Northern blot analysis detected at least 3 CSP variants in all 8 human tissues examined. Western blot analysis of human blood detected CSP at an apparent molecular mass of 35 kD. Treatment with a deacylating agent caused a downward shift of 7 kD in apparent mass. </p><p>Tobaben et al. (2001) showed that the 198-amino acid rat Csp protein contains an N-terminal J domain, followed by a cysteine string and a C-terminal domain. They noted that most of the cysteines are palmitoylated and are required for membrane targeting of Csp. </p><p>Using real-time RT-PCR, Fernandez-Chacon et al. (2004) detected Csp-alpha in mouse brain and testis. </p><p>Natochin et al. (2005) stated that rat Csp has 2 binding sites for G proteins, one that overlaps the J domain and binds G-alpha subunits (see GNAS, 139320), and another between the J domain and cysteine string that binds G-beta (see GNB1, 139380) and/or the G-alpha-beta-gamma (see GNG2, 606981) trimer. </p>
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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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<span class="mim-text-font">
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<p>Tobaben et al. (2001) showed that rat Csp interacted with Sgt (SGTA; 603419) and Hsc70 (HSPA8; 600816) in a complex located on the synaptic vesicle surface. The complex functioned as an ATP-dependent chaperone that reactivated a denatured substrate. Sgt overexpression in cultured rat hippocampal neurons inhibited neurotransmitter release, suggesting that the Csp/Sgt/Hsc70 complex is important for maintenance of a normal synapse. </p><p>Miller et al. (2003) stated that rat Csp binds both the N-type calcium channel (see 601012) and G protein beta-gamma subunits in vitro, and that these associations give rise to tonic G protein inhibition of the calcium channel. They showed that an N-terminal fragment of human huntingtin (HTT; 613004) with an expanded polyglutamine tract blocked association of Csp with G proteins and eliminated Csp's tonic G protein inhibition of N-type calcium channels. In contrast, an N-terminal huntingtin fragment without an expanded polyglutamine tract did not alter association of Csp with G proteins and had no effect on channel inhibition by Csp. </p><p>Natochin et al. (2005) showed that rat Csp stimulated GDP/GTP exchange on G-alpha-S. Modulation of G proteins by Csp was, in turn, regulated by Hsc70 and Sgt. </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>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Gross (2011) mapped the DNAJC5 gene to chromosome 20q13.33 based on an alignment of the DNAJC5 sequence (GenBank BC053642) with the genomic sequence (GRCh37).</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In a Czech family with an autosomal dominant form of Kufs disease, ceroid neuronal lipofuscinosis-4 (CLN4; 162350), Noskova et al. (2011) identified a heterozygous 3-bp deletion in the DNAJC5 gene (346_348delCTC; 611203.0001), resulting in deletion of leu116. The mutation was found by a combination of linkage analysis, copy-number analysis, gene-expression analysis, and exome sequencing of candidate genes. Screening of this gene in 20 additional families identified pathogenic mutations, including a novel missense mutation (L115R; 611203.0002), in 4. Two of the families had been reported by Josephson et al. (2001) and Nijssen et al. (2002). The patients had onset of rapidly progressive neurodegenerative disorder with onset in the third or fourth decades. </p><p>In patients with CLN4, Benitez et al. (2011) and Velinov et al. (2012) found the same 2 heterozygous mutations in the DNAJC5 gene as those reported by Noskova et al. (2011), thus confirming the findings. Benitez et al. (2011) studied the family originally reported by Josephson et al. (2001), and Velinov et al. (2012) studied the Parry family originally reported by Boehme et al. (1971). </p><p>By linkage analysis combined with exome sequencing in the large family (Parry family) with adult-onset CLN reported by Boehme et al. (1971), Cadieux-Dion et al. (2013) also identified heterozygosity for the same 3-bp deletion mutation in the DNAJC5 gene (611203.0001). The mutation was confirmed by Sanger sequencing, was not found in 380 control chromosomes, and segregated with the disorder in the family. The American patient reported by Noskova et al. (2011) who carried this mutation was found to be from the Parry family. Cadieux-Dion et al. (2013) also identified the leu116del mutation in affected members of a family from Alabama reported by Burneo et al. (2003). Haplotype analysis did not show a founder effect between the 2 families, suggesting that it is a recurrent mutation. Cadieux-Dion et al. (2013) also identified a heterozygous L115R mutation in the DNAJC5 gene (611203.0002) in 1 of 6 additional patients with the disorder; this patient had no family history. Overall, DNAJC5 mutations accounted for 38% of cases with unexplained adult-onset NCL in their cohort, with the mutations occurring at mutational hotspots. </p><p>In 2 Canadian sibs with CLN4, Jedlickova et al. (2020) identified a heterozygous 30-bp duplication in the DNAJC5 gene (c.370_399dup; 611203.0003), resulting in an in-frame duplication involving the central core motif of the cysteine-string domain of the CSP-alpha protein. On initial targeted Sanger sequencing of the DNAJC5 gene, the 30-bp duplication was not identified, likely due to preferential amplification of the wildtype allele and allelic drop out of the mutated allele. Furthermore, the 30-bp duplication was initially missed on whole-exome sequencing and was identified only after exome reanalysis was performed with altered variant detection thresholds. Redesign of Sanger sequencing parameters confirmed the presence of the 30-bp duplication mutant. Expression of the mutant protein in CAD5 cells demonstrated abnormal cellular localization, abnormal palmitoylation, and formation of high molecular weight aggregates. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Fernandez-Chacon et al. (2004) found that Csp-alpha -/- mice appeared normal at birth but developed a progressive lethal phenotype that manifested as muscle weakness and a sensorimotor disorder at 2 to 4 weeks of age. Analysis of synaptic transmission in Csp-alpha -/- neuromuscular junctions and at the Calyx of Held synapse revealed normal Ca(2+) channel function and Ca(2+)-dependent exocytosis. However, synapses showed progressively worsening presynaptic degeneration, with persistent vacuoles, proliferation of multilamellar bodies, and protrusion of Schwann cell fingers into the neuromuscular nerve terminal. Coppola and Gundersen (1996) concluded that the degeneration of Csp-alpha -/- synapses appeared to occur in a use-dependent manner and that CSP-alpha is required to maintain the integrity of synapses in the face of use-dependent stress. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>3 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 CEROID LIPOFUSCINOSIS, NEURONAL, 4 (KUFS TYPE)</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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DNAJC5, 3-BP DEL, 346CTC
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<br />
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SNP: rs587776892,
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ClinVar: RCV000023878, RCV000632720
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In affected members of a Czech family with an autosomal dominant form of Kufs disease, neuronal ceroid lipofuscinosis-4 (CLN4; 162350), Noskova et al. (2011) identified a heterozygous 3-bp deletion (346_348delCTC) in the DNAJC5 gene, resulting in a deletion of leu116 (Leu116del) in a conserved region of the cysteine-string domain of the protein. Screening of this gene in 20 additional families identified this mutation in 1 affected American patient who had a family history of the disorder. The patients had onset of rapidly progressive neurodegenerative disorder with onset in the third or fourth decades. Haplotype analysis did not suggest a common origin. The mutation was not found in 200 controls. In vitro functional expression in CAD5 neuronal cells showed that the mutant protein had abnormal diffuse intracellular localization and abnormal colocalization with markers for the endoplasmic reticulum and Golgi apparatus. Immunoblot analysis indicated that the mutant protein was less efficiently palmitoylated compared to wildtype. Analysis of brain tissue from affected individuals showed significantly reduced immunostaining for DNAJC5 in the cerebral cortex compared to controls. </p><p>Benitez et al. (2011) identified the heterozygous 346_348delCTC mutation in affected members of a family with CLN4. The mutation, which was found by Sanger sequencing, was not present in the dbSNP (build 134) or 1000 Genomes Project databases or in more than 3,200 control chromosomes. These findings confirmed the report of Noskova et al. (2011). Molecular modeling studies predicted that the mutation may weaken membrane binding by decreasing affinity of the protein for the membrane. Other functional studies were not performed. </p><p>Velinov et al. (2012) identified the 3-bp deletion mutation in affected members of the original Parry family with CLN4 (Boehme et al., 1971). Affected individuals also carried a heterozygous 1430A-G transition in the PRPF6 gene (613979), resulting in an asn477-to-ser (N477S) substitution at a highly conserved residue. The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Neither mutation was found in 2,100 control individuals. Both changes occurred within about 75 kb on chromosome 20 and were likely linked on a rare haplotype. Velinov et al. (2012) noted that a PRPF6 mutation has been associated with retinitis pigmentosa-60 (RP60; 613983) and that some members of the Parry family had unspecified visual problems, suggesting that it may be a phenotypic modifier in this family. </p><p>By linkage analysis combined with exome sequencing in the large family (Parry family) with adult-onset CLN reported by Boehme et al. (1971), Cadieux-Dion et al. (2013) identified a heterozygous 346_348del mutation. The mutation was confirmed by Sanger sequencing, was not found in 380 control chromosomes, and segregated with the disorder in the family. The American patient reported by Noskova et al. (2011) who carried this mutation was found to be from the Parry family. Cadieux-Dion et al. (2013) also identified the leu116del mutation in affected members of a family from Alabama reported by Burneo et al. (2003), even though the mutation in this family had not been found by Noskova et al. (2011). Haplotype analysis did not show a founder effect between the 2 families, suggesting that it is a recurrent mutation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 CEROID LIPOFUSCINOSIS, NEURONAL, 4 (KUFS TYPE)</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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DNAJC5, LEU115ARG
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<br />
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SNP: rs387907043,
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gnomAD: rs387907043,
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ClinVar: RCV000023879, RCV002466414
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In affected members of 2 unrelated families and 1 patient with autosomal dominant Kufs disease (CLN4; 162350), Noskova et al. (2011) identified a heterozygous 344T-G transversion in the DNAJC5 gene, resulting in a leu115-to-arg (L115R) substitution in a conserved residue in the cysteine-string domain of the protein. Two of the families had been reported by Josephson et al. (2001) and Nijssen et al. (2002). The mutation was not found in 200 controls. Haplotype analysis did not suggest a common origin. In vitro functional expression in CAD5 neuronal cells showed that the mutant protein had abnormal diffuse intracellular localization and abnormal colocalization with markers for the endoplasmic reticulum and Golgi apparatus. Immunoblot analysis indicated that the mutant protein was less efficiently palmitoylated compared to wildtype. Analysis of brain tissue from affected individuals showed absence of immunostaining for DNAJC5 in synaptic regions in both the cerebral and cerebellar cortex compared to controls. However, there was some evidence for an insoluble DNAJC5-containing aggregate in brain lysate. </p><p>Benitez et al. (2011) identified a heterozygous L115R mutation in affected members of a large family with CLN4 originally reported by Josephson et al. (2001). The mutation, which was found by whole-exome sequencing and filtered against the dbSNP (build 130) and 1000 Genomes Project databases as well as 59 in-house exomes, was confirmed by Sanger sequencing to segregate with the disorder in the family. It was also absent in an additional 1,600 controls. Molecular modeling studies predicted that the mutation may weaken membrane binding by decreasing affinity of the protein for the membrane. Other functional studies were not performed. These findings confirmed the report of Noskova et al. (2011). </p><p>Velinov et al. (2012) identified a heterozygous L115R mutation in a patient with CLN4B. </p><p>Cadieux-Dion et al. (2013) identified a heterozygous L115R mutation in a patient with sporadic occurrence of CLN4B. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 CEROID LIPOFUSCINOSIS, NEURONAL, 4 (KUFS TYPE)</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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DNAJC5, 30-BP DUP, NT370
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<br />
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SNP: rs1600887859,
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ClinVar: RCV000850191
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 sibs with autosomal dominant Kufs disease (CLN4; 162350), Jedlickova et al. (2020) identified a heterozygous 30-bp duplication (c.370_399dup, NM_025219.2) in exon 4 of the DNAJC5 gene, resulting in an in-frame duplication (Cys124_Cys133). The mutation was identified by whole-exome sequencing and confirmed by Sanger sequencing. The duplication encodes the central core motif of the cysteine-string domain of CSP-alpha. Expression of mutant CSP-alpha in CAD5 cells showed abnormal cellular localization with reduced expression in the plasma membrane, abnormal palmitoylation with only the nonpalmitoylated form present, and formation of high molecular weight aggregates. </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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Benitez, B. A., Alvarado, D., Cai, Y., Mayo, K., Chakraverty, S., Norton, J., Morris, J. C., Sands, M. S., Goate, A., Cruchaga, C.
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<strong>Exome-sequencing confirms DNAJC5 mutations as cause of adult neuronal ceroid-lipofuscinosis.</strong>
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PLoS One 6: e26741, 2011. Note: Electronic Article.
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[PubMed: 22073189]
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[Full Text: https://doi.org/10.1371/journal.pone.0026741]
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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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Boehme, D. H., Cottrell, J. C., Leonberg, S. C., Zeman, W.
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<strong>A dominant form of neuronal ceroid-lipofuscinosis.</strong>
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Brain 94: 745-760, 1971.
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[PubMed: 5132971]
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[Full Text: https://doi.org/10.1093/brain/94.4.745]
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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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Burneo, J. G., Arnold, T., Palmer, C. A., Kuzniecky, R. I., Oh, S. J., Faught, E.
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<strong>Adult-onset neuronal ceroid lipofuscinosis (Kufs disease) with autosomal dominant inheritance in Alabama.</strong>
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Epilepsia 44: 841-846, 2003.
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[PubMed: 12790899]
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[Full Text: https://doi.org/10.1046/j.1528-1157.2003.39802.x]
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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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Cadieux-Dion, M., Andermann, E., Lachance-Touchette, P., Ansorge, O., Meloche, C., Barnabe, A., Kuzniecky, R. I., Andermann, F., Faught, E., Leonberg, S., Damiano, J. A., Berkovic, S. F., Rouleau, G. A., Cossette, P.
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<strong>Recurrent mutations in DNAJC5 cause autosomal dominant Kufs disease.</strong>
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Clin. Genet. 83: 571-575, 2013.
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[PubMed: 22978711]
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[Full Text: https://doi.org/10.1111/cge.12020]
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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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Coppola, T., Gundersen, C.
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<strong>Widespread expression of human cysteine string proteins.</strong>
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FEBS Lett. 391: 269-272, 1996.
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[PubMed: 8764987]
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[Full Text: https://doi.org/10.1016/0014-5793(96)00750-8]
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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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Fernandez-Chacon, R., Wolfel, M., Nishimune, H., Tabares, L., Schmitz, F., Castellano-Munoz, M., Rosenmund, C., Montesinos, M. L., Sanes, J. R., Schneggenburger, R., Sudhof, T. C.
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<strong>The synaptic vesicle protein CSP-alpha prevents presynaptic degeneration.</strong>
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Neuron 42: 237-251, 2004.
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[PubMed: 15091340]
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[Full Text: https://doi.org/10.1016/s0896-6273(04)00190-4]
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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. 4/28/2011.
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Jedlickova, I., Cadieux-Dion, M., Pristoupilova, A., Stranecky, V., Hartmannova, H., Hodanova, K., Baresova, V., Hulkova, H., Sikora, J., Noskova, L., Musalkova, D., Vyletal, P., Sovova, J., Cossette, P., Andermann, E., Andermann, F., Kmoch, S., Adult NCL Gene Discovery Consortium.
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<strong>Autosomal-dominant adult neuronal ceroid lipofuscinosis caused by duplication in DNAJC5 initially missed by Sanger and whole-exome sequencing.</strong>
|
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Europ. J. Hum. Genet. 28: 783-789, 2020.
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[PubMed: 31919451]
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[Full Text: https://doi.org/10.1038/s41431-019-0567-2]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Josephson, S. A., Schmidt, R. E., Millsap, P., McManus, D. Q., Morris, J. C.
|
|
<strong>Autosomal dominant Kufs' disease: a cause of early onset dementia.</strong>
|
|
J. Neurol. Sci. 188: 51-60, 2001.
|
|
|
|
|
|
[PubMed: 11489285]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0022-510x(01)00546-9]
|
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|
|
|
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|
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|
|
|
|
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|
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|
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Miller, L. C., Swayne, L. A., Chen, L., Feng, Z.-P., Wacker, J. L., Muchowski, P. J., Zamponi, G. W., Braun, J. E. A.
|
|
<strong>Cysteine string protein (CSP) inhibition of N-type calcium channels is blocked by mutant huntingtin.</strong>
|
|
J. Biol. Chem. 278: 53072-53081, 2003.
|
|
|
|
|
|
[PubMed: 14570907]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M306230200]
|
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|
|
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|
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|
|
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Natochin, M., Campbell, T. N., Barren, B., Miller, L. C., Hameed, S., Artemyev, N. O., Braun, J. E. A.
|
|
<strong>Characterization of the G-alpha-s regulator cysteine string protein.</strong>
|
|
J. Biol. Chem. 280: 30236-30241, 2005.
|
|
|
|
|
|
[PubMed: 15972823]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M500722200]
|
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|
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|
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Nijssen, P. C. G., Brusse, E., Leyten, A. C. M., Martin, J. J., Teepen, J. L. J. M., Roos, R. A. C.
|
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<strong>Autosomal dominant adult neuronal ceroid lipofuscinosis: parkinsonism due to both striatal and nigral dysfunction.</strong>
|
|
Mov. Disord. 17: 482-487, 2002.
|
|
|
|
|
|
[PubMed: 12112194]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/mds.10104]
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</p>
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</li>
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<li>
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Noskova, L., Stranecky, V., Hartmannova, H., Pristoupilova, A., Baresova, V., Ivanek, R., Hulkova, H., Jahnova, H., van der Zee, J., Staropoli, J. F., Sims, K. B., Tyynela, J., Van Broeckhoven, C., Nijssen, P. C. G., Mole, S. E., Elleder, M., Kmoch, S.
|
|
<strong>Mutations in DNAJC5, encoding cysteine-string protein alpha, cause autosomal-dominant adult-onset neuronal ceroid lipofuscinosis.</strong>
|
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Am. J. Hum. Genet. 89: 241-252, 2011. Note: Erratum: Am. J. Hum. Genet. 89: 589 only, 2011.
|
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|
|
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[PubMed: 21820099]
|
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|
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[Full Text: https://doi.org/10.1016/j.ajhg.2011.07.003]
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</p>
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</li>
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<li>
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Tobaben, S., Thakur, P., Fernandez-Chacon, R., Sudhof, T. C., Rettig, J., Stahl, B.
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<strong>A trimeric protein complex functions as a synaptic chaperone machine.</strong>
|
|
Neuron 31: 987-999, 2001.
|
|
|
|
|
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[PubMed: 11580898]
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[Full Text: https://doi.org/10.1016/s0896-6273(01)00427-5]
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Velinov, M., Dolzhanskaya, N., Gonzalez, M., Powell, E., Konidari, I., Hulme, W., Staropoli, J. F., Xin, W., Wen, G. Y., Barone, R., Coppel, S. H., Sims, K., Brown, W. T., Zuchner, S.
|
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<strong>Mutations in the gene DNAJC5 cause autosomal dominant Kufs disease in a proportion of cases: study of the Parry family and 8 other families.</strong>
|
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PLoS One 7: e29729, 2012. Note: Electronic Article. Erratum published online.
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[PubMed: 22235333]
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[Full Text: https://doi.org/10.1371/journal.pone.0029729]
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Hilary J. Vernon - updated : 09/02/2022<br>Cassandra L. Kniffin - updated : 6/30/2014<br>Cassandra L. Kniffin - updated : 6/3/2013<br>Cassandra L. Kniffin - updated : 9/15/2011<br>Matthew B. Gross - updated : 4/28/2011<br>Patricia A. Hartz - updated : 4/19/2011
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