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Entry
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- *608102 - CLN5 INTRACELLULAR TRAFFICKING PROTEIN; CLN5
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- OMIM
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<div id="mimSearch" class="hidden-print">
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<div class="container">
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<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
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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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<div class="input-group-btn">
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<ul class="dropdown-menu dropdown-menu-right">
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<li class="dropdown-header">
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Advanced Search
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</li>
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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>
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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>
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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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<a href="/history"> Search History </a>
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</form>
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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">*608102</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="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#biochemicalFeatures">Biochemical Features</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="#geneStructure">Gene Structure</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/608102">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>
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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=ENSG00000102805;t=ENST00000377453" 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=1203" 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=608102" 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=ENSG00000102805;t=ENST00000377453" 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_001366624,NM_006493" 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_006493" 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=608102" 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=07619&isoform_id=07619_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/CLN5" 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/3342386,119600967,119600968,187608866,193786746,194384290,1489858243,1489865991" 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/O75503" 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=1203" 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=ENSG00000102805;t=ENST00000377453" 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=CLN5" 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=CLN5" 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+1203" 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/CLN5" 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:1203" 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/1203" 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=chr13&hgg_gene=ENST00000638147.2&hgg_start=76992081&hgg_end=77005117&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">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
|
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</a>
|
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</span>
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</span>
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</div>
|
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:2076" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/cln5" 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=608102[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=608102[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/ENSG00000102805" 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=CLN5" 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=CLN5" 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=CLN5" 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="http://www.ucl.ac.uk/ncl/" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=CLN5&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/PA26603" 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">
|
|
<span class="panel-title">
|
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<span class="small">
|
|
<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:2076" 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://www.mousephenotype.org/data/genes/MGI:2442253" 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/CLN5#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:2442253" 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/1203/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://omia.org/OMIA001482/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=1203" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-060908-1" 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">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
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|
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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:1203" 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=CLN5&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>
|
|
<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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|
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<div>
|
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|
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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>
|
|
608102
|
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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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|
|
CLN5 INTRACELLULAR TRAFFICKING PROTEIN; CLN5
|
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|
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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>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
CLN5 GENE
|
|
</span>
|
|
</h4>
|
|
</div>
|
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</div>
|
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<div>
|
|
<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=CLN5" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">CLN5</a></em></strong>
|
|
</span>
|
|
</p>
|
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</div>
|
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/13/231?start=-3&limit=10&highlight=231">13q22.3</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr13:76992081-77005117&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'})">13:76,992,081-77,005,117</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
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|
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
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|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/13/231?start=-3&limit=10&highlight=231">
|
|
13q22.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
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<p><a href="#9" class="mim-tip-reference" title="Savukoski, M., Klockars, T., Holmberg, V., Santavuori, P., Lander, E. S., Peltonen, L. <strong>CLN5, a novel gene encoding a putative transmembrane protein mutated in Finnish variant late infantile neuronal ceroid lipofuscinosis.</strong> Nature Genet. 19: 286-288, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9662406/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9662406</a>] [<a href="https://doi.org/10.1038/975" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9662406">Savukoski et al. (1998)</a> reported positional cloning of the CLN5 gene, which encodes a putative 407-amino acid transmembrane protein. Northern blot analysis showed relatively weak hybridization signals of approximately 2.0, 3.0, and 4.5 kb in all human tissues tested. Additionally, a 5.5-kb signal was seen in skeletal muscle. Overall observation suggested expression of CLN5 in all human tissues, with up to 5-fold variation in expression levels. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9662406" 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 immunofluorescence microscopy, <a href="#3" class="mim-tip-reference" title="Isosomppi, J., Vesa, J., Jalanko, A., Peltonen, L. <strong>Lysosomal localization of the neuronal ceroid lipofuscinosis CLN5 protein.</strong> Hum. Molec. Genet. 11: 885-891, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11971870/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11971870</a>] [<a href="https://doi.org/10.1093/hmg/11.8.885" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11971870">Isosomppi et al. (2002)</a> demonstrated that wildtype CLN5 is predominantly targeted to lysosomes. Immunoprecipitation analysis recognized a 60-kD polypeptide, which was reduced to 38-40 kD by deglycosylation. Glycosylated polypeptides were also observed in the media, suggesting that the CLN5 polypeptide may represent a soluble lysosomal glycoprotein, rather than an integral transmembrane protein as predicted previously. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11971870" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#5" class="mim-tip-reference" title="Larkin, H., Ribeiro, M. G., Lavoie, C. <strong>Topology and membrane anchoring of the lysosomal storage disease-related protein CLN5.</strong> Hum. Mutat. 34: 1688-1697, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24038957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24038957</a>] [<a href="https://doi.org/10.1002/humu.22443" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24038957">Larkin et al. (2013)</a> identified 2 hydrophobic regions predicted to function as transmembrane domains near the N and C termini of CLN5, a signal peptide cleavage site following the putative N-terminal transmembrane domain, and 8 putative N-glycosylation sites. However, protease digestion, extraction, and solubilization experiments performed on CLN5 expressed in HeLa and HEK293 cells revealed that the C-terminal hydrophobic region adopts an amphipathic helix formation and is not a transmembrane domain. The findings suggested a model where CLN5 is synthesized as a precursor with a transmembrane domain near its N terminus. CLN5 is rapidly glycosylated and cleaved at the signal cleavage site after the transmembrane domain, resulting in a mature CLN5 protein located entirely within the lumen of the intracellular compartments. The amphipathic helix near the C terminus mediates tight association of the mature glycosylated protein with intraluminal membranes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24038957" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By in vitro studies in COS-1 and HeLa cells, <a href="#10" class="mim-tip-reference" title="Schmiedt, M.-L., Bessa, C., Heine, C., Ribeiro, M. G., Jalanko, A., Kyttala, A. <strong>The neuronal ceroid lipofuscinosis protein CLN5: new insights into cellular maturation, transport, and consequences of mutations.</strong> Hum. Mutat. 31: 356-365, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20052765/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20052765</a>] [<a href="https://doi.org/10.1002/humu.21195" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20052765">Schmiedt et al. (2010)</a> found that the CLN5 protein is proteolytically cleaved in the endoplasmic reticulum (ER), and that the mature soluble protein is transported to lysosomes in a manner independent of the mannose-6-phosphate mechanism. The protein is highly glycosylated. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20052765" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#9" class="mim-tip-reference" title="Savukoski, M., Klockars, T., Holmberg, V., Santavuori, P., Lander, E. S., Peltonen, L. <strong>CLN5, a novel gene encoding a putative transmembrane protein mutated in Finnish variant late infantile neuronal ceroid lipofuscinosis.</strong> Nature Genet. 19: 286-288, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9662406/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9662406</a>] [<a href="https://doi.org/10.1038/975" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9662406">Savukoski et al. (1998)</a> determined that the CLN5 gene contains 4 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9662406" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#2" class="mim-tip-reference" title="Gross, M. B. <strong>Personal Communication.</strong> Baltimore, Md. 6/4/2014."None>Gross (2014)</a> mapped the CLN5 gene to chromosome 13q22.3 based on an alignment of the CLN5 sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=BC146274" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">BC146274</a>) with the genomic sequence (GRCh37).</p>
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<p>In patients with neuronal ceroid lipofuscinosis-5 (CLN5; <a href="/entry/256731">256731</a>), <a href="#9" class="mim-tip-reference" title="Savukoski, M., Klockars, T., Holmberg, V., Santavuori, P., Lander, E. S., Peltonen, L. <strong>CLN5, a novel gene encoding a putative transmembrane protein mutated in Finnish variant late infantile neuronal ceroid lipofuscinosis.</strong> Nature Genet. 19: 286-288, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9662406/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9662406</a>] [<a href="https://doi.org/10.1038/975" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9662406">Savukoski et al. (1998)</a> identified 3 different homozygous mutations in the CLN5 gene (<a href="#0001">608102.0001</a>-<a href="#0003">608102.0003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9662406" 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="#3" class="mim-tip-reference" title="Isosomppi, J., Vesa, J., Jalanko, A., Peltonen, L. <strong>Lysosomal localization of the neuronal ceroid lipofuscinosis CLN5 protein.</strong> Hum. Molec. Genet. 11: 885-891, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11971870/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11971870</a>] [<a href="https://doi.org/10.1093/hmg/11.8.885" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11971870">Isosomppi et al. (2002)</a> noted that the most common CLN5 mutation among patients with the Finnish variant of neuronal ceroid lipofuscinosis is a 2-bp deletion, resulting in a truncated protein (<a href="#0001">608102.0001</a>). Immunofluorescence-based localization of the mutant protein showed defective intracellular lysosomal targeting. The authors suggested that the pathogenesis of this type of CLN5 may be associated with defective lysosomal trafficking and prevention of normal biologic function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11971870" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By in vitro studies in cultured cells, <a href="#10" class="mim-tip-reference" title="Schmiedt, M.-L., Bessa, C., Heine, C., Ribeiro, M. G., Jalanko, A., Kyttala, A. <strong>The neuronal ceroid lipofuscinosis protein CLN5: new insights into cellular maturation, transport, and consequences of mutations.</strong> Hum. Mutat. 31: 356-365, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20052765/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20052765</a>] [<a href="https://doi.org/10.1002/humu.21195" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20052765">Schmiedt et al. (2010)</a> demonstrated that disease-associated CLN5 mutations perturb intracellular trafficking to lysosomes. For example, about 90% of the D279N (<a href="#0003">608102.0003</a>) mutant was found in the ER, but only 10% made it to lysosomes. The R112H (<a href="#0004">608102.0004</a>) mutant mainly localized to the ER and possibly to the Golgi apparatus, but was not found in lysosomes. The level of lysosomal targeting did not correlate with disease onset, suggesting that CLN5 may also function outside of lysosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20052765" 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 10 of 47 non-Finnish patients with a clinical diagnosis of NCL, <a href="#13" class="mim-tip-reference" title="Xin, W., Mullen, T. E., Kiely, R., Min, J., Feng, X., Cao, Y., O'Malley, L., Shen, Y., Chu-Shore, C., Mole, S. E., Goebel, H. H., Sims, K. <strong>CLN5 mutations are frequent in juvenile and late-onset non-Finnish patients with NCL.</strong> Neurology 74: 565-571, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20157158/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20157158</a>] [<a href="https://doi.org/10.1212/WNL.0b013e3181cff70d" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20157158">Xin et al. (2010)</a> identified 14 mutations in the CLN5 gene, including 11 novel mutations (see, e.g., <a href="#0006">608102.0006</a>-<a href="#0008">608102.0008</a>). Twelve of the 20 disease alleles resulted in premature termination of the protein. The findings suggested that CLN5 mutations may be more common than previously believed, can be found in non-Finnish patients, and can be found in patients with later onset. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20157158" 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="#5" class="mim-tip-reference" title="Larkin, H., Ribeiro, M. G., Lavoie, C. <strong>Topology and membrane anchoring of the lysosomal storage disease-related protein CLN5.</strong> Hum. Mutat. 34: 1688-1697, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24038957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24038957</a>] [<a href="https://doi.org/10.1002/humu.22443" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24038957">Larkin et al. (2013)</a> determined that CLN5 with mutations causing loss of its C-terminal amphipathic helix, such as glu352 to ter (E352X; <a href="#0005">608102.0005</a>), was not tightly associated with membranes and was degraded. All mutations studied by <a href="#5" class="mim-tip-reference" title="Larkin, H., Ribeiro, M. G., Lavoie, C. <strong>Topology and membrane anchoring of the lysosomal storage disease-related protein CLN5.</strong> Hum. Mutat. 34: 1688-1697, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24038957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24038957</a>] [<a href="https://doi.org/10.1002/humu.22443" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24038957">Larkin et al. (2013)</a> induced relocalization of CLN5 to the ER. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24038957" 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 sibs with neuronal ceroid lipofuscinosis, <a href="#1" class="mim-tip-reference" title="El Haddad, S., Khoury, M., Daoud, M., Kantar, R., Harati, H., Mousallem, T., Alzate, O., Meyer, B., Boustany, R.-M. <strong>CLN5 and CLN8 protein association with ceramide synthase: biochemical and proteomic approaches.</strong> Electrophoresis 33: 3798-3809, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23160995/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23160995</a>] [<a href="https://doi.org/10.1002/elps.201200472" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23160995">El Haddad et al. (2012)</a> identified a homozygous truncating mutation in the CLN5 gene (Q232X; <a href="#0010">608102.0010</a>). The mutation, which was found by homozygosity mapping and candidate gene sequencing, segregated with the disorder in the family. The patients had originally been classified as having CLN9 (<a href="/entry/609055">609055</a>) by Schulz et al. (<a href="#11" class="mim-tip-reference" title="Schulz, A., Dhar, S., Rylova, S., Dbaibo, G., Alroy, J., Hagel, C., Artacho, I., Kohlschutter, A., Lin, S., Boustany, R.-M. <strong>Impaired cell adhesion and apoptosis in a novel CLN9 Batten disease variant.</strong> Ann. Neurol. 56: 342-350, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15349861/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15349861</a>] [<a href="https://doi.org/10.1002/ana.20187" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15349861">2004</a>, <a href="#12" class="mim-tip-reference" title="Schulz, A., Mousallem, T., Venkataramani, M., Persaud-Sawin, D.-A., Zucker, A., Luberto, C., Bielawska, A., Bielawski, J., Holthuis, J. C. M., Jazwinski, S. M., Kozhaya, L., Dbaibo, G. S., Boustany, R.-M. N. <strong>The CLN9 protein, a regulator of dihydroceramide synthase.</strong> J. Biol. Chem. 281: 2784-2794, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16303764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16303764</a>] [<a href="https://doi.org/10.1074/jbc.M509483200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16303764">2006</a>) who observed that patient fibroblasts showed decreased dihydroceramide synthase activity (see, e.g., CERS1; <a href="/entry/606919">606919</a>). <a href="#12" class="mim-tip-reference" title="Schulz, A., Mousallem, T., Venkataramani, M., Persaud-Sawin, D.-A., Zucker, A., Luberto, C., Bielawska, A., Bielawski, J., Holthuis, J. C. M., Jazwinski, S. M., Kozhaya, L., Dbaibo, G. S., Boustany, R.-M. N. <strong>The CLN9 protein, a regulator of dihydroceramide synthase.</strong> J. Biol. Chem. 281: 2784-2794, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16303764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16303764</a>] [<a href="https://doi.org/10.1074/jbc.M509483200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16303764">Schulz et al. (2006)</a> found that patient cells showed partial correction of growth defects and apoptosis when transfected with CLN8 (<a href="/entry/607837">607837</a>) and several human ceramide synthase genes, all of which increase dihydroceramide synthase activity. <a href="#12" class="mim-tip-reference" title="Schulz, A., Mousallem, T., Venkataramani, M., Persaud-Sawin, D.-A., Zucker, A., Luberto, C., Bielawska, A., Bielawski, J., Holthuis, J. C. M., Jazwinski, S. M., Kozhaya, L., Dbaibo, G. S., Boustany, R.-M. N. <strong>The CLN9 protein, a regulator of dihydroceramide synthase.</strong> J. Biol. Chem. 281: 2784-2794, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16303764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16303764</a>] [<a href="https://doi.org/10.1074/jbc.M509483200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16303764">Schulz et al. (2006)</a> concluded that the protein implicated in CLN9 may be a regulator of dihydroceramide synthase. <a href="#1" class="mim-tip-reference" title="El Haddad, S., Khoury, M., Daoud, M., Kantar, R., Harati, H., Mousallem, T., Alzate, O., Meyer, B., Boustany, R.-M. <strong>CLN5 and CLN8 protein association with ceramide synthase: biochemical and proteomic approaches.</strong> Electrophoresis 33: 3798-3809, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23160995/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23160995</a>] [<a href="https://doi.org/10.1002/elps.201200472" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23160995">El Haddad et al. (2012)</a> found that CLN5-null cells had increased growth rates and increased apoptosis compared to controls, and these defects could be corrected by transfection with wildtype CLN5. CLN5-null cells also had decreased levels of sphingolipids downstream of ceramide synthase. CLN5-null patient fibroblasts showed absence of ACTG1 (<a href="/entry/102560">102560</a>) from CERS1 protein complexes as well as absence of ACTG1-bound proteins, including vimentin and several histone proteins, which may have explained the cellular phenotype of growth defects. The findings suggested a possible association of CLN8 with CLN5, such as CLN8 and CLN5 acting in a concerted manner to activate ceramide synthesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15349861+23160995+16303764" 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="#4" class="mim-tip-reference" title="Kopra, O., Vesa, J., von Schantz, C., Manninen, T., Minye, H., Fabritius, A.-L., Rapola, J., van Diggelen, O. P., Saarela, J., Jalanko, A., Peltonen, L. <strong>A mouse model for Finnish variant late infantile neuronal ceroid lipofuscinosis, CLN5, reveals neuropathology associated with early aging.</strong> Hum. Molec. Genet. 13: 2893-2906, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15459177/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15459177</a>] [<a href="https://doi.org/10.1093/hmg/ddh312" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15459177">Kopra et al. (2004)</a> developed a mouse model of neuronal ceroid lipofuscinosis-5 by targeted deletion of exon 3 of the mouse Cln5 gene. The Cln5 -/- mice showed loss of vision and accumulation of autofluorescent storage material in CNS and peripheral tissues, without prominent brain atrophy. Electron microscopy of the storage material revealed a mixture of lamellar profiles including fingerprint profiles and curvilinear and rectilinear bodies. Prominent loss of a subset of GABAergic interneurons in several brain areas was also seen. Brain transcript profiling revealed altered expression of several genes involved in neurodegeneration, as well as in defense and immune response, typical of age-associated changes in the CNS. Downregulation of structural components of myelin was detected, consistent with the hypomyelination seen in the human CLN5 patients. Since the Cln5 -/- mice did not exhibit significant brain atrophy, <a href="#4" class="mim-tip-reference" title="Kopra, O., Vesa, J., von Schantz, C., Manninen, T., Minye, H., Fabritius, A.-L., Rapola, J., van Diggelen, O. P., Saarela, J., Jalanko, A., Peltonen, L. <strong>A mouse model for Finnish variant late infantile neuronal ceroid lipofuscinosis, CLN5, reveals neuropathology associated with early aging.</strong> Hum. Molec. Genet. 13: 2893-2906, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15459177/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15459177</a>] [<a href="https://doi.org/10.1093/hmg/ddh312" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15459177">Kopra et al. (2004)</a> suggested that these mice could serve as a model for studying the molecular processes associated with advanced aging. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15459177" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In 17 families with the Finnish variant of late infantile neuronal ceroid lipofuscinosis (CLN5; <a href="/entry/256731">256731</a>), <a href="#9" class="mim-tip-reference" title="Savukoski, M., Klockars, T., Holmberg, V., Santavuori, P., Lander, E. S., Peltonen, L. <strong>CLN5, a novel gene encoding a putative transmembrane protein mutated in Finnish variant late infantile neuronal ceroid lipofuscinosis.</strong> Nature Genet. 19: 286-288, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9662406/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9662406</a>] [<a href="https://doi.org/10.1038/975" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9662406">Savukoski et al. (1998)</a> identified a homozygous 2-bp deletion in exon 4 of the CLN5 gene, resulting in a tyr392-to-ter (Y392X) substitution. The predicted protein had 391 amino acids instead of the 407 predicted in controls. The mutation was identified in 34 of 36 disease chromosomes, making it the most common CLN5 mutation in Finland. In a high-risk area on the west coast of Finland, a carrier frequency of 1 in 24 was found in 1 community and approximately 1 in 100 in the rest of the area. No carriers were observed among 100 control individuals from elsewhere in Finland. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9662406" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a single Finnish family with the Finnish variant late infantile type of neuronal ceroid lipofuscinosis (CLN5; <a href="/entry/256731">256731</a>), <a href="#9" class="mim-tip-reference" title="Savukoski, M., Klockars, T., Holmberg, V., Santavuori, P., Lander, E. S., Peltonen, L. <strong>CLN5, a novel gene encoding a putative transmembrane protein mutated in Finnish variant late infantile neuronal ceroid lipofuscinosis.</strong> Nature Genet. 19: 286-288, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9662406/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9662406</a>] [<a href="https://doi.org/10.1038/975" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9662406">Savukoski et al. (1998)</a> found homozygosity for a 1517G-A transition in exon 1 of the CLN5 gene, causing a trp75-to-ter (W75X) nonsense change and a predicted protein of only 74 amino acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9662406" 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> rs28940280 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28940280;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/rs28940280?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=rs28940280" 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=rs28940280" 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=RCV000002675 OR RCV000989152 OR RCV004689404" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002675, RCV000989152, RCV004689404" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002675...</a>
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<p>In a Dutch patient with the Finnish variant late infantile type of neuronal ceroid lipofuscinosis-5 (CLN5; <a href="/entry/256731">256731</a>), <a href="#9" class="mim-tip-reference" title="Savukoski, M., Klockars, T., Holmberg, V., Santavuori, P., Lander, E. S., Peltonen, L. <strong>CLN5, a novel gene encoding a putative transmembrane protein mutated in Finnish variant late infantile neuronal ceroid lipofuscinosis.</strong> Nature Genet. 19: 286-288, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9662406/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9662406</a>] [<a href="https://doi.org/10.1038/975" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9662406">Savukoski et al. (1998)</a> found the only non-Finnish mutation in the CLN5 gene: homozygosity for a 2127G-A transition, causing an asp279-to-asn (D279N) amino acid substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9662406" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 CEROID LIPOFUSCINOSIS, NEURONAL, 5</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104894386 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894386;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/rs104894386?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=rs104894386" 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=rs104894386" 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=RCV000002676 OR RCV000698933 OR RCV003128567" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002676, RCV000698933, RCV003128567" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002676...</a>
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<p>In affected members of a large consanguineous Colombian family with juvenile-onset neuronal ceroid lipofuscinosis-5 (CLN5; <a href="/entry/256731">256731</a>), <a href="#8" class="mim-tip-reference" title="Pineda-Trujillo, N., Cornejo, W., Carrizosa, J., Wheeler, R. B., Munera, S., Valencia, A., Agudelo-Arango, J., Cogollo, A., Anderson, G., Bedoya, G., Mole, S. E., Ruiz-Linares, A. <strong>A CLN5 mutation causing an atypical neuronal ceroid lipofuscinosis of juvenile onset.</strong> Neurology 64: 740-742, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15728307/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15728307</a>] [<a href="https://doi.org/10.1212/01.WNL.0000151974.44980.F1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15728307">Pineda-Trujillo et al. (2005)</a> identified a homozygous 1627G-A transition in the CLN5 gene, resulting in an arg112-to-his (R112H) substitution. The mutation occurs in a residue conserved among rodent, amphibian, and bird species, and was not identified in 58 control chromosomes. Onset of the disorder was at age 9 years, consistent with juvenile onset. The findings showed that the disorder occurs outside of northern Europe. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15728307" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 CEROID LIPOFUSCINOSIS, NEURONAL, 5</strong>
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CLN5, GLU352TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908292 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908292;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=rs121908292" 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=rs121908292" 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=RCV000002677 OR RCV002512684" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002677, RCV002512684" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002677...</a>
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<p>In 2 affected members of a family from Newfoundland with neuronal ceroid lipofuscinosis-5 (CLN5; <a href="/entry/256731">256731</a>), <a href="#7" class="mim-tip-reference" title="Moore, S. J., Buckley, D. J., MacMillan, A., Marshall, H. D., Steele, L., Ray, P. N., Nawaz, Z., Baskin, B., Frecker, M., Carr, S. M., Ives, E., Parfrey, P. S. <strong>The clinical and genetic epidemiology of neuronal ceroid lipofuscinosis in Newfoundland.</strong> Clin. Genet. 74: 213-222, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18684116/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18684116</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2008.01054.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18684116">Moore et al. (2008)</a> identified a homozygous 1054G-T transversion in the CLN5 gene, resulting in a glu352-to-ter (E352X) substitution. The family had originated from the southwest of England. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18684116" 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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<h4>
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<strong>.0006 CEROID LIPOFUSCINOSIS, NEURONAL, 5</strong>
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CLN5, CYS126TYR
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs267606738 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606738;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=rs267606738" 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=rs267606738" 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=RCV000002678 OR RCV001039257" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002678, RCV001039257" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002678...</a>
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<p>In a non-Finnish Caucasian patient with late-onset of neuronal ceroid lipofuscinosis-5 (CLN5; <a href="/entry/256731">256731</a>), <a href="#13" class="mim-tip-reference" title="Xin, W., Mullen, T. E., Kiely, R., Min, J., Feng, X., Cao, Y., O'Malley, L., Shen, Y., Chu-Shore, C., Mole, S. E., Goebel, H. H., Sims, K. <strong>CLN5 mutations are frequent in juvenile and late-onset non-Finnish patients with NCL.</strong> Neurology 74: 565-571, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20157158/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20157158</a>] [<a href="https://doi.org/10.1212/WNL.0b013e3181cff70d" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20157158">Xin et al. (2010)</a> identified compound heterozygosity for 2 missense mutations in the CLN5 gene: a 377G-A transition in exon 2, resulting in a cys126-to-tyr (C126Y) substitution in a highly conserved residue, and the Y374C mutation (<a href="#0007">608102.0007</a>). The patient presented at age 17 years with cognitive regression and visual loss, which progressed to seizures and motor difficulties in the following few years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20157158" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0007 CEROID LIPOFUSCINOSIS, NEURONAL, 5</strong>
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CLN5, TYR374CYS
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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> rs148862100 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs148862100;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/rs148862100?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=rs148862100" 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=rs148862100" 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=RCV000002679 OR RCV000493479 OR RCV001318349" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002679, RCV000493479, RCV001318349" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002679...</a>
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<p>In 2 unrelated non-Finnish Caucasian patients with late-onset neuronal ceroid lipofuscinosis-5 (CLN5; <a href="/entry/256731">256731</a>), <a href="#13" class="mim-tip-reference" title="Xin, W., Mullen, T. E., Kiely, R., Min, J., Feng, X., Cao, Y., O'Malley, L., Shen, Y., Chu-Shore, C., Mole, S. E., Goebel, H. H., Sims, K. <strong>CLN5 mutations are frequent in juvenile and late-onset non-Finnish patients with NCL.</strong> Neurology 74: 565-571, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20157158/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20157158</a>] [<a href="https://doi.org/10.1212/WNL.0b013e3181cff70d" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20157158">Xin et al. (2010)</a> identified a 1121A-G transition in exon 4 of the CLN5 gene, resulting in a tyr374-to-cys (Y374C) substitution in a highly conserved residue. One patient was compound heterozygous for the Y374C and C126Y (<a href="#0006">608102.0006</a>) mutations, and the other was compound heterozygous for the Y374C mutation and an intragenic deletion of exon 4 (<a href="#0008">608102.0008</a>), encompassing at least nucleotides 907 to 1094. Both patients had onset of symptoms at age 17 years, with ultimate visual loss, motor difficulties, seizures, and cognitive regression. <a href="#13" class="mim-tip-reference" title="Xin, W., Mullen, T. E., Kiely, R., Min, J., Feng, X., Cao, Y., O'Malley, L., Shen, Y., Chu-Shore, C., Mole, S. E., Goebel, H. H., Sims, K. <strong>CLN5 mutations are frequent in juvenile and late-onset non-Finnish patients with NCL.</strong> Neurology 74: 565-571, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20157158/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20157158</a>] [<a href="https://doi.org/10.1212/WNL.0b013e3181cff70d" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20157158">Xin et al. (2010)</a> postulated that the Y374C mutant protein retains some residual function, which may explain the later onset in these patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20157158" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0008" class="mim-anchor"></a>
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<strong>.0008 CEROID LIPOFUSCINOSIS, NEURONAL, 5</strong>
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CLN5, EX4DEL
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<p>For discussion of the exon 4 deletion encompassing at least nucleotides 907 to 1094 in the CLN5 gene that was found in compound heterozygous state in a patient with late-onset neuronal ceroid lipofuscinosis-5 (CLN5; <a href="/entry/256731">256731</a>) by <a href="#13" class="mim-tip-reference" title="Xin, W., Mullen, T. E., Kiely, R., Min, J., Feng, X., Cao, Y., O'Malley, L., Shen, Y., Chu-Shore, C., Mole, S. E., Goebel, H. H., Sims, K. <strong>CLN5 mutations are frequent in juvenile and late-onset non-Finnish patients with NCL.</strong> Neurology 74: 565-571, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20157158/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20157158</a>] [<a href="https://doi.org/10.1212/WNL.0b013e3181cff70d" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20157158">Xin et al. (2010)</a>, see <a href="#0007">608102.0007</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20157158" 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> rs730882146 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs730882146;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/rs730882146?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=rs730882146" 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=rs730882146" 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=RCV000161918 OR RCV002515118" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000161918, RCV002515118" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000161918...</a>
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<p>In 2 sibs, born of consanguineous Italian parents, with onset of neuronal ceroid lipofuscinosis-5 (CLN5; <a href="/entry/256731">256731</a>) in their mid-fifties, <a href="#6" class="mim-tip-reference" title="Mancini, C., Nassani, S., Guo, Y., Chen, Y., Giorgio, E., Brussino, A., Di Gregorio, E., Cavalieri, S., Lo Buono, N., Funaro, A., Pizio, N. R., Nmezi, B., Kyttala, A., Santorelli, F. M., Padiath, Q. S., Hakonarson, H., Zhang, H., Brusco, A. <strong>Adult-onset autosomal recessive ataxia associated with neuronal ceroid lipofuscinosis type 5 gene (CLN5) mutations.</strong> J. Neurol. 262: 173-178, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25359263/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25359263</a>] [<a href="https://doi.org/10.1007/s00415-014-7553-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25359263">Mancini et al. (2015)</a> identified a homozygous c.935G-A transition in the CLN5 gene, resulting in a ser312-to-asn (S312N) substitution at a highly conserved residue. The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing; an unaffected brother was heterozygous for the variant. In vitro functional expression studies in HEK293 cells showed that the mutant protein was abnormally retained in the endoplasmic reticulum and did not reach the lysosome. The mutant protein was also unstable compared to wildtype. The patients had an unusually late onset of symptoms, and presented with cerebellar ataxia and progressive cognitive decline. <a href="#6" class="mim-tip-reference" title="Mancini, C., Nassani, S., Guo, Y., Chen, Y., Giorgio, E., Brussino, A., Di Gregorio, E., Cavalieri, S., Lo Buono, N., Funaro, A., Pizio, N. R., Nmezi, B., Kyttala, A., Santorelli, F. M., Padiath, Q. S., Hakonarson, H., Zhang, H., Brusco, A. <strong>Adult-onset autosomal recessive ataxia associated with neuronal ceroid lipofuscinosis type 5 gene (CLN5) mutations.</strong> J. Neurol. 262: 173-178, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25359263/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25359263</a>] [<a href="https://doi.org/10.1007/s00415-014-7553-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25359263">Mancini et al. (2015)</a> postulated that the S312N variant was a hypomorphic allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25359263" 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">rs869312751 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs869312751;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=rs869312751" 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=rs869312751" 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=RCV000210062 OR RCV002282043" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000210062, RCV002282043" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000210062...</a>
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<p>In 2 sibs with neuronal ceroid lipofuscinosis-5 (CLN5; <a href="/entry/256731">256731</a>), <a href="#1" class="mim-tip-reference" title="El Haddad, S., Khoury, M., Daoud, M., Kantar, R., Harati, H., Mousallem, T., Alzate, O., Meyer, B., Boustany, R.-M. <strong>CLN5 and CLN8 protein association with ceramide synthase: biochemical and proteomic approaches.</strong> Electrophoresis 33: 3798-3809, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23160995/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23160995</a>] [<a href="https://doi.org/10.1002/elps.201200472" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23160995">El Haddad et al. (2012)</a> identified a homozygous c.694C-T transition in the CLN5 gene, resulting in a gln232-to-ter (Q232X) substitution. The mutation, which was found by homozygosity mapping and candidate gene sequencing, segregated with the disorder in the family. Western blot analysis of patient fibroblasts confirmed the presence of a truncated CLN5 protein. The patients had previously been reported by <a href="#11" class="mim-tip-reference" title="Schulz, A., Dhar, S., Rylova, S., Dbaibo, G., Alroy, J., Hagel, C., Artacho, I., Kohlschutter, A., Lin, S., Boustany, R.-M. <strong>Impaired cell adhesion and apoptosis in a novel CLN9 Batten disease variant.</strong> Ann. Neurol. 56: 342-350, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15349861/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15349861</a>] [<a href="https://doi.org/10.1002/ana.20187" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15349861">Schulz et al. (2004)</a> as having neuronal ceroid lipofuscinosis-9 (CLN9; <a href="/entry/609055">609055</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15349861+23160995" 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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El Haddad, S., Khoury, M., Daoud, M., Kantar, R., Harati, H., Mousallem, T., Alzate, O., Meyer, B., Boustany, R.-M.
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<strong>CLN5 and CLN8 protein association with ceramide synthase: biochemical and proteomic approaches.</strong>
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Electrophoresis 33: 3798-3809, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23160995/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23160995</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23160995" 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/elps.201200472" target="_blank">Full Text</a>]
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<strong>Personal Communication.</strong>
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Baltimore, Md. 6/4/2014.
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Isosomppi, J., Vesa, J., Jalanko, A., Peltonen, L.
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<strong>Lysosomal localization of the neuronal ceroid lipofuscinosis CLN5 protein.</strong>
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Hum. Molec. Genet. 11: 885-891, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11971870/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11971870</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11971870" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/11.8.885" target="_blank">Full Text</a>]
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Kopra, O., Vesa, J., von Schantz, C., Manninen, T., Minye, H., Fabritius, A.-L., Rapola, J., van Diggelen, O. P., Saarela, J., Jalanko, A., Peltonen, L.
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<strong>A mouse model for Finnish variant late infantile neuronal ceroid lipofuscinosis, CLN5, reveals neuropathology associated with early aging.</strong>
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Hum. Molec. Genet. 13: 2893-2906, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15459177/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15459177</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15459177" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<strong>Topology and membrane anchoring of the lysosomal storage disease-related protein CLN5.</strong>
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Hum. Mutat. 34: 1688-1697, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24038957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24038957</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24038957" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Mancini, C., Nassani, S., Guo, Y., Chen, Y., Giorgio, E., Brussino, A., Di Gregorio, E., Cavalieri, S., Lo Buono, N., Funaro, A., Pizio, N. R., Nmezi, B., Kyttala, A., Santorelli, F. M., Padiath, Q. S., Hakonarson, H., Zhang, H., Brusco, A.
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<strong>Adult-onset autosomal recessive ataxia associated with neuronal ceroid lipofuscinosis type 5 gene (CLN5) mutations.</strong>
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J. Neurol. 262: 173-178, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25359263/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25359263</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25359263" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Moore, S. J., Buckley, D. J., MacMillan, A., Marshall, H. D., Steele, L., Ray, P. N., Nawaz, Z., Baskin, B., Frecker, M., Carr, S. M., Ives, E., Parfrey, P. S.
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<strong>The clinical and genetic epidemiology of neuronal ceroid lipofuscinosis in Newfoundland.</strong>
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Clin. Genet. 74: 213-222, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18684116/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18684116</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18684116" 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/j.1399-0004.2008.01054.x" target="_blank">Full Text</a>]
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</p>
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<a id="8" class="mim-anchor"></a>
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<a id="Pineda-Trujillo2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Pineda-Trujillo, N., Cornejo, W., Carrizosa, J., Wheeler, R. B., Munera, S., Valencia, A., Agudelo-Arango, J., Cogollo, A., Anderson, G., Bedoya, G., Mole, S. E., Ruiz-Linares, A.
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<strong>A CLN5 mutation causing an atypical neuronal ceroid lipofuscinosis of juvenile onset.</strong>
|
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Neurology 64: 740-742, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15728307/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15728307</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15728307" 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/10.1212/01.WNL.0000151974.44980.F1" 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="Savukoski1998" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Savukoski, M., Klockars, T., Holmberg, V., Santavuori, P., Lander, E. S., Peltonen, L.
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|
<strong>CLN5, a novel gene encoding a putative transmembrane protein mutated in Finnish variant late infantile neuronal ceroid lipofuscinosis.</strong>
|
|
Nature Genet. 19: 286-288, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9662406/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9662406</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9662406" 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/10.1038/975" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="10" class="mim-anchor"></a>
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<a id="Schmiedt2010" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Schmiedt, M.-L., Bessa, C., Heine, C., Ribeiro, M. G., Jalanko, A., Kyttala, A.
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<strong>The neuronal ceroid lipofuscinosis protein CLN5: new insights into cellular maturation, transport, and consequences of mutations.</strong>
|
|
Hum. Mutat. 31: 356-365, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20052765/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20052765</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20052765" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/humu.21195" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="11" class="mim-anchor"></a>
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<a id="Schulz2004" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Schulz, A., Dhar, S., Rylova, S., Dbaibo, G., Alroy, J., Hagel, C., Artacho, I., Kohlschutter, A., Lin, S., Boustany, R.-M.
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|
<strong>Impaired cell adhesion and apoptosis in a novel CLN9 Batten disease variant.</strong>
|
|
Ann. Neurol. 56: 342-350, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15349861/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15349861</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15349861" 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/ana.20187" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="12" class="mim-anchor"></a>
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<a id="Schulz2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Schulz, A., Mousallem, T., Venkataramani, M., Persaud-Sawin, D.-A., Zucker, A., Luberto, C., Bielawska, A., Bielawski, J., Holthuis, J. C. M., Jazwinski, S. M., Kozhaya, L., Dbaibo, G. S., Boustany, R.-M. N.
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<strong>The CLN9 protein, a regulator of dihydroceramide synthase.</strong>
|
|
J. Biol. Chem. 281: 2784-2794, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16303764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16303764</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16303764" 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.M509483200" 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="Xin2010" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Xin, W., Mullen, T. E., Kiely, R., Min, J., Feng, X., Cao, Y., O'Malley, L., Shen, Y., Chu-Shore, C., Mole, S. E., Goebel, H. H., Sims, K.
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|
<strong>CLN5 mutations are frequent in juvenile and late-onset non-Finnish patients with NCL.</strong>
|
|
Neurology 74: 565-571, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20157158/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20157158</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20157158" 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/10.1212/WNL.0b013e3181cff70d" target="_blank">Full Text</a>]
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</p>
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</div>
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</ol>
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<div>
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<br />
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</div>
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</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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</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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Cassandra L. Kniffin - updated : 3/11/2016
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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 : 2/23/2015<br>Matthew B. Gross - updated : 6/4/2014<br>Patricia A. Hartz - updated : 6/4/2014<br>Cassandra L. Kniffin - updated : 5/5/2010<br>Cassandra L. Kniffin - updated : 4/8/2010<br>Cassandra L. Kniffin - updated : 4/28/2009<br>George E. Tiller - updated : 5/21/2007<br>Cassandra L. Kniffin - updated : 5/24/2005
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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<div 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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Cassandra L. Kniffin : 9/17/2003
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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="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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alopez : 08/19/2024
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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 : 08/12/2020<br>carol : 08/11/2020<br>carol : 10/20/2016<br>carol : 03/23/2016<br>alopez : 3/15/2016<br>ckniffin : 3/11/2016<br>carol : 2/24/2015<br>mcolton : 2/23/2015<br>ckniffin : 2/23/2015<br>mgross : 6/4/2014<br>mcolton : 6/4/2014<br>carol : 9/19/2013<br>wwang : 5/11/2010<br>ckniffin : 5/5/2010<br>wwang : 4/9/2010<br>ckniffin : 4/8/2010<br>wwang : 5/11/2009<br>ckniffin : 4/28/2009<br>wwang : 5/31/2007<br>terry : 5/21/2007<br>ckniffin : 3/21/2006<br>wwang : 6/1/2005<br>wwang : 5/25/2005<br>ckniffin : 5/24/2005<br>carol : 6/25/2004<br>carol : 9/23/2003<br>ckniffin : 9/23/2003<br>ckniffin : 9/17/2003
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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 class="container visible-print-block">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 608102
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</span>
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</h3>
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<div>
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<h3>
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<span class="mim-font">
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CLN5 INTRACELLULAR TRAFFICKING PROTEIN; CLN5
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</span>
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</h3>
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</div>
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<div>
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<br />
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<div >
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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CLN5 GENE
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: CLN5</em></strong>
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</span>
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</p>
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</div>
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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: 13q22.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 13:76,992,081-77,005,117 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
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13q22.3
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</span>
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</td>
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<td>
|
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<span class="mim-font">
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Ceroid lipofuscinosis, neuronal, 5
|
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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256731
|
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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Autosomal recessive
|
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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3
|
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Savukoski et al. (1998) reported positional cloning of the CLN5 gene, which encodes a putative 407-amino acid transmembrane protein. Northern blot analysis showed relatively weak hybridization signals of approximately 2.0, 3.0, and 4.5 kb in all human tissues tested. Additionally, a 5.5-kb signal was seen in skeletal muscle. Overall observation suggested expression of CLN5 in all human tissues, with up to 5-fold variation in expression levels. </p><p>By immunofluorescence microscopy, Isosomppi et al. (2002) demonstrated that wildtype CLN5 is predominantly targeted to lysosomes. Immunoprecipitation analysis recognized a 60-kD polypeptide, which was reduced to 38-40 kD by deglycosylation. Glycosylated polypeptides were also observed in the media, suggesting that the CLN5 polypeptide may represent a soluble lysosomal glycoprotein, rather than an integral transmembrane protein as predicted previously. </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>Biochemical Features</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>Larkin et al. (2013) identified 2 hydrophobic regions predicted to function as transmembrane domains near the N and C termini of CLN5, a signal peptide cleavage site following the putative N-terminal transmembrane domain, and 8 putative N-glycosylation sites. However, protease digestion, extraction, and solubilization experiments performed on CLN5 expressed in HeLa and HEK293 cells revealed that the C-terminal hydrophobic region adopts an amphipathic helix formation and is not a transmembrane domain. The findings suggested a model where CLN5 is synthesized as a precursor with a transmembrane domain near its N terminus. CLN5 is rapidly glycosylated and cleaved at the signal cleavage site after the transmembrane domain, resulting in a mature CLN5 protein located entirely within the lumen of the intracellular compartments. The amphipathic helix near the C terminus mediates tight association of the mature glycosylated protein with intraluminal membranes. </p>
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</span>
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<div>
|
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<br />
|
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Gene Function</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
|
|
<p>By in vitro studies in COS-1 and HeLa cells, Schmiedt et al. (2010) found that the CLN5 protein is proteolytically cleaved in the endoplasmic reticulum (ER), and that the mature soluble protein is transported to lysosomes in a manner independent of the mannose-6-phosphate mechanism. The protein is highly glycosylated. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Savukoski et al. (1998) determined that the CLN5 gene contains 4 exons. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Gross (2014) mapped the CLN5 gene to chromosome 13q22.3 based on an alignment of the CLN5 sequence (GenBank BC146274) 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 patients with neuronal ceroid lipofuscinosis-5 (CLN5; 256731), Savukoski et al. (1998) identified 3 different homozygous mutations in the CLN5 gene (608102.0001-608102.0003). </p><p>Isosomppi et al. (2002) noted that the most common CLN5 mutation among patients with the Finnish variant of neuronal ceroid lipofuscinosis is a 2-bp deletion, resulting in a truncated protein (608102.0001). Immunofluorescence-based localization of the mutant protein showed defective intracellular lysosomal targeting. The authors suggested that the pathogenesis of this type of CLN5 may be associated with defective lysosomal trafficking and prevention of normal biologic function. </p><p>By in vitro studies in cultured cells, Schmiedt et al. (2010) demonstrated that disease-associated CLN5 mutations perturb intracellular trafficking to lysosomes. For example, about 90% of the D279N (608102.0003) mutant was found in the ER, but only 10% made it to lysosomes. The R112H (608102.0004) mutant mainly localized to the ER and possibly to the Golgi apparatus, but was not found in lysosomes. The level of lysosomal targeting did not correlate with disease onset, suggesting that CLN5 may also function outside of lysosomes. </p><p>In 10 of 47 non-Finnish patients with a clinical diagnosis of NCL, Xin et al. (2010) identified 14 mutations in the CLN5 gene, including 11 novel mutations (see, e.g., 608102.0006-608102.0008). Twelve of the 20 disease alleles resulted in premature termination of the protein. The findings suggested that CLN5 mutations may be more common than previously believed, can be found in non-Finnish patients, and can be found in patients with later onset. </p><p>Larkin et al. (2013) determined that CLN5 with mutations causing loss of its C-terminal amphipathic helix, such as glu352 to ter (E352X; 608102.0005), was not tightly associated with membranes and was degraded. All mutations studied by Larkin et al. (2013) induced relocalization of CLN5 to the ER. </p><p>In 2 sibs with neuronal ceroid lipofuscinosis, El Haddad et al. (2012) identified a homozygous truncating mutation in the CLN5 gene (Q232X; 608102.0010). The mutation, which was found by homozygosity mapping and candidate gene sequencing, segregated with the disorder in the family. The patients had originally been classified as having CLN9 (609055) by Schulz et al. (2004, 2006) who observed that patient fibroblasts showed decreased dihydroceramide synthase activity (see, e.g., CERS1; 606919). Schulz et al. (2006) found that patient cells showed partial correction of growth defects and apoptosis when transfected with CLN8 (607837) and several human ceramide synthase genes, all of which increase dihydroceramide synthase activity. Schulz et al. (2006) concluded that the protein implicated in CLN9 may be a regulator of dihydroceramide synthase. El Haddad et al. (2012) found that CLN5-null cells had increased growth rates and increased apoptosis compared to controls, and these defects could be corrected by transfection with wildtype CLN5. CLN5-null cells also had decreased levels of sphingolipids downstream of ceramide synthase. CLN5-null patient fibroblasts showed absence of ACTG1 (102560) from CERS1 protein complexes as well as absence of ACTG1-bound proteins, including vimentin and several histone proteins, which may have explained the cellular phenotype of growth defects. The findings suggested a possible association of CLN8 with CLN5, such as CLN8 and CLN5 acting in a concerted manner to activate ceramide synthesis. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>Animal Model</strong>
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|
</span>
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</h4>
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|
</div>
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<span class="mim-text-font">
|
|
<p>Kopra et al. (2004) developed a mouse model of neuronal ceroid lipofuscinosis-5 by targeted deletion of exon 3 of the mouse Cln5 gene. The Cln5 -/- mice showed loss of vision and accumulation of autofluorescent storage material in CNS and peripheral tissues, without prominent brain atrophy. Electron microscopy of the storage material revealed a mixture of lamellar profiles including fingerprint profiles and curvilinear and rectilinear bodies. Prominent loss of a subset of GABAergic interneurons in several brain areas was also seen. Brain transcript profiling revealed altered expression of several genes involved in neurodegeneration, as well as in defense and immune response, typical of age-associated changes in the CNS. Downregulation of structural components of myelin was detected, consistent with the hypomyelination seen in the human CLN5 patients. Since the Cln5 -/- mice did not exhibit significant brain atrophy, Kopra et al. (2004) suggested that these mice could serve as a model for studying the molecular processes associated with advanced aging. </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>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
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</span>
|
|
<strong>10 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
|
|
</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0001 CEROID LIPOFUSCINOSIS, NEURONAL, 5</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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CLN5, 2-BP DEL, 2467AT
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<br />
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SNP: rs386833969,
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|
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ClinVar: RCV000002673, RCV000484812, RCV000684967
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In 17 families with the Finnish variant of late infantile neuronal ceroid lipofuscinosis (CLN5; 256731), Savukoski et al. (1998) identified a homozygous 2-bp deletion in exon 4 of the CLN5 gene, resulting in a tyr392-to-ter (Y392X) substitution. The predicted protein had 391 amino acids instead of the 407 predicted in controls. The mutation was identified in 34 of 36 disease chromosomes, making it the most common CLN5 mutation in Finland. In a high-risk area on the west coast of Finland, a carrier frequency of 1 in 24 was found in 1 community and approximately 1 in 100 in the rest of the area. No carriers were observed among 100 control individuals from elsewhere in Finland. </p>
|
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</span>
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</div>
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<div>
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|
<br />
|
|
</div>
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|
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 CEROID LIPOFUSCINOSIS, NEURONAL, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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|
|
CLN5, TRP75TER
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|
<br />
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|
|
SNP: rs104894385,
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|
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gnomAD: rs104894385,
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|
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|
|
ClinVar: RCV000002674, RCV000689128
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|
|
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|
|
</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a single Finnish family with the Finnish variant late infantile type of neuronal ceroid lipofuscinosis (CLN5; 256731), Savukoski et al. (1998) found homozygosity for a 1517G-A transition in exon 1 of the CLN5 gene, causing a trp75-to-ter (W75X) nonsense change and a predicted protein of only 74 amino acids. </p>
|
|
</span>
|
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</div>
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<div>
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<br />
|
|
</div>
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</div>
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<div>
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|
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 CEROID LIPOFUSCINOSIS, NEURONAL, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
CLN5, ASP279ASN
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|
|
|
<br />
|
|
|
|
SNP: rs28940280,
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|
|
|
|
|
gnomAD: rs28940280,
|
|
|
|
|
|
ClinVar: RCV000002675, RCV000989152, RCV004689404
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Dutch patient with the Finnish variant late infantile type of neuronal ceroid lipofuscinosis-5 (CLN5; 256731), Savukoski et al. (1998) found the only non-Finnish mutation in the CLN5 gene: homozygosity for a 2127G-A transition, causing an asp279-to-asn (D279N) amino acid substitution. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
|
</div>
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|
|
|
</div>
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|
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 CEROID LIPOFUSCINOSIS, NEURONAL, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CLN5, ARG112HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894386,
|
|
|
|
|
|
gnomAD: rs104894386,
|
|
|
|
|
|
ClinVar: RCV000002676, RCV000698933, RCV003128567
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a large consanguineous Colombian family with juvenile-onset neuronal ceroid lipofuscinosis-5 (CLN5; 256731), Pineda-Trujillo et al. (2005) identified a homozygous 1627G-A transition in the CLN5 gene, resulting in an arg112-to-his (R112H) substitution. The mutation occurs in a residue conserved among rodent, amphibian, and bird species, and was not identified in 58 control chromosomes. Onset of the disorder was at age 9 years, consistent with juvenile onset. The findings showed that the disorder occurs outside of northern Europe. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 CEROID LIPOFUSCINOSIS, NEURONAL, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CLN5, GLU352TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908292,
|
|
|
|
|
|
|
|
ClinVar: RCV000002677, RCV002512684
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 affected members of a family from Newfoundland with neuronal ceroid lipofuscinosis-5 (CLN5; 256731), Moore et al. (2008) identified a homozygous 1054G-T transversion in the CLN5 gene, resulting in a glu352-to-ter (E352X) substitution. The family had originated from the southwest of England. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 CEROID LIPOFUSCINOSIS, NEURONAL, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CLN5, CYS126TYR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs267606738,
|
|
|
|
|
|
|
|
ClinVar: RCV000002678, RCV001039257
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a non-Finnish Caucasian patient with late-onset of neuronal ceroid lipofuscinosis-5 (CLN5; 256731), Xin et al. (2010) identified compound heterozygosity for 2 missense mutations in the CLN5 gene: a 377G-A transition in exon 2, resulting in a cys126-to-tyr (C126Y) substitution in a highly conserved residue, and the Y374C mutation (608102.0007). The patient presented at age 17 years with cognitive regression and visual loss, which progressed to seizures and motor difficulties in the following few years. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 CEROID LIPOFUSCINOSIS, NEURONAL, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CLN5, TYR374CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs148862100,
|
|
|
|
|
|
gnomAD: rs148862100,
|
|
|
|
|
|
ClinVar: RCV000002679, RCV000493479, RCV001318349
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 unrelated non-Finnish Caucasian patients with late-onset neuronal ceroid lipofuscinosis-5 (CLN5; 256731), Xin et al. (2010) identified a 1121A-G transition in exon 4 of the CLN5 gene, resulting in a tyr374-to-cys (Y374C) substitution in a highly conserved residue. One patient was compound heterozygous for the Y374C and C126Y (608102.0006) mutations, and the other was compound heterozygous for the Y374C mutation and an intragenic deletion of exon 4 (608102.0008), encompassing at least nucleotides 907 to 1094. Both patients had onset of symptoms at age 17 years, with ultimate visual loss, motor difficulties, seizures, and cognitive regression. Xin et al. (2010) postulated that the Y374C mutant protein retains some residual function, which may explain the later onset in these patients. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 CEROID LIPOFUSCINOSIS, NEURONAL, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CLN5, EX4DEL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1555274312,
|
|
|
|
|
|
|
|
ClinVar: RCV000002680
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the exon 4 deletion encompassing at least nucleotides 907 to 1094 in the CLN5 gene that was found in compound heterozygous state in a patient with late-onset neuronal ceroid lipofuscinosis-5 (CLN5; 256731) by Xin et al. (2010), see 608102.0007. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 CEROID LIPOFUSCINOSIS, NEURONAL, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CLN5, SER312ASN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs730882146,
|
|
|
|
|
|
gnomAD: rs730882146,
|
|
|
|
|
|
ClinVar: RCV000161918, RCV002515118
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sibs, born of consanguineous Italian parents, with onset of neuronal ceroid lipofuscinosis-5 (CLN5; 256731) in their mid-fifties, Mancini et al. (2015) identified a homozygous c.935G-A transition in the CLN5 gene, resulting in a ser312-to-asn (S312N) substitution at a highly conserved residue. The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing; an unaffected brother was heterozygous for the variant. In vitro functional expression studies in HEK293 cells showed that the mutant protein was abnormally retained in the endoplasmic reticulum and did not reach the lysosome. The mutant protein was also unstable compared to wildtype. The patients had an unusually late onset of symptoms, and presented with cerebellar ataxia and progressive cognitive decline. Mancini et al. (2015) postulated that the S312N variant was a hypomorphic allele. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
|
</div>
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|
|
</div>
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 CEROID LIPOFUSCINOSIS, NEURONAL, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
CLN5, GLN232TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs869312751,
|
|
|
|
|
|
|
|
ClinVar: RCV000210062, RCV002282043
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
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<p>In 2 sibs with neuronal ceroid lipofuscinosis-5 (CLN5; 256731), El Haddad et al. (2012) identified a homozygous c.694C-T transition in the CLN5 gene, resulting in a gln232-to-ter (Q232X) substitution. The mutation, which was found by homozygosity mapping and candidate gene sequencing, segregated with the disorder in the family. Western blot analysis of patient fibroblasts confirmed the presence of a truncated CLN5 protein. The patients had previously been reported by Schulz et al. (2004) as having neuronal ceroid lipofuscinosis-9 (CLN9; 609055). </p>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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Gross, M. B.
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<strong>Personal Communication.</strong>
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Kopra, O., Vesa, J., von Schantz, C., Manninen, T., Minye, H., Fabritius, A.-L., Rapola, J., van Diggelen, O. P., Saarela, J., Jalanko, A., Peltonen, L.
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Larkin, H., Ribeiro, M. G., Lavoie, C.
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<strong>Topology and membrane anchoring of the lysosomal storage disease-related protein CLN5.</strong>
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Hum. Mutat. 34: 1688-1697, 2013.
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Mancini, C., Nassani, S., Guo, Y., Chen, Y., Giorgio, E., Brussino, A., Di Gregorio, E., Cavalieri, S., Lo Buono, N., Funaro, A., Pizio, N. R., Nmezi, B., Kyttala, A., Santorelli, F. M., Padiath, Q. S., Hakonarson, H., Zhang, H., Brusco, A.
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<strong>Adult-onset autosomal recessive ataxia associated with neuronal ceroid lipofuscinosis type 5 gene (CLN5) mutations.</strong>
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Moore, S. J., Buckley, D. J., MacMillan, A., Marshall, H. D., Steele, L., Ray, P. N., Nawaz, Z., Baskin, B., Frecker, M., Carr, S. M., Ives, E., Parfrey, P. S.
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<strong>The clinical and genetic epidemiology of neuronal ceroid lipofuscinosis in Newfoundland.</strong>
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Pineda-Trujillo, N., Cornejo, W., Carrizosa, J., Wheeler, R. B., Munera, S., Valencia, A., Agudelo-Arango, J., Cogollo, A., Anderson, G., Bedoya, G., Mole, S. E., Ruiz-Linares, A.
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<strong>A CLN5 mutation causing an atypical neuronal ceroid lipofuscinosis of juvenile onset.</strong>
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Neurology 64: 740-742, 2005.
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<p class="mim-text-font">
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Savukoski, M., Klockars, T., Holmberg, V., Santavuori, P., Lander, E. S., Peltonen, L.
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<strong>CLN5, a novel gene encoding a putative transmembrane protein mutated in Finnish variant late infantile neuronal ceroid lipofuscinosis.</strong>
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Nature Genet. 19: 286-288, 1998.
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[PubMed: 9662406]
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[Full Text: https://doi.org/10.1038/975]
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<li>
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<p class="mim-text-font">
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Schmiedt, M.-L., Bessa, C., Heine, C., Ribeiro, M. G., Jalanko, A., Kyttala, A.
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<strong>The neuronal ceroid lipofuscinosis protein CLN5: new insights into cellular maturation, transport, and consequences of mutations.</strong>
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Hum. Mutat. 31: 356-365, 2010.
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[PubMed: 20052765]
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<li>
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Schulz, A., Dhar, S., Rylova, S., Dbaibo, G., Alroy, J., Hagel, C., Artacho, I., Kohlschutter, A., Lin, S., Boustany, R.-M.
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<strong>Impaired cell adhesion and apoptosis in a novel CLN9 Batten disease variant.</strong>
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Ann. Neurol. 56: 342-350, 2004.
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[PubMed: 15349861]
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[Full Text: https://doi.org/10.1002/ana.20187]
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<li>
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<p class="mim-text-font">
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Schulz, A., Mousallem, T., Venkataramani, M., Persaud-Sawin, D.-A., Zucker, A., Luberto, C., Bielawska, A., Bielawski, J., Holthuis, J. C. M., Jazwinski, S. M., Kozhaya, L., Dbaibo, G. S., Boustany, R.-M. N.
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<strong>The CLN9 protein, a regulator of dihydroceramide synthase.</strong>
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J. Biol. Chem. 281: 2784-2794, 2006.
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[PubMed: 16303764]
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[Full Text: https://doi.org/10.1074/jbc.M509483200]
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</p>
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Xin, W., Mullen, T. E., Kiely, R., Min, J., Feng, X., Cao, Y., O'Malley, L., Shen, Y., Chu-Shore, C., Mole, S. E., Goebel, H. H., Sims, K.
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<strong>CLN5 mutations are frequent in juvenile and late-onset non-Finnish patients with NCL.</strong>
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Neurology 74: 565-571, 2010.
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[PubMed: 20157158]
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[Full Text: https://doi.org/10.1212/WNL.0b013e3181cff70d]
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