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<title>
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Entry
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- *610746 - DOLICHOL KINASE; DOLK
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- OMIM
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</ul>
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</nav>
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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="mimSearchStart" name="start" value="1" />
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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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<div class="col-lg-8 col-md-8 col-sm-8 col-xs-8">
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<div class="form-group">
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<div class="input-group">
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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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<button type="submit" id="mimEntrySearchSubmit" class="btn btn-default" style="width: 5em;"><span class="glyphicon glyphicon-search"></span></button>
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<button type="button" class="btn btn-default dropdown-toggle" data-toggle="dropdown"> Options <span class="caret"></span></button>
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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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<li role="separator" class="divider"></li>
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<li>
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<a href="/history"> Search History </a>
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</ul>
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</div>
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</form>
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<p />
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<div id="mimAlertBanner">
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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">*610746</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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<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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</li>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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</li>
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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>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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</li>
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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>
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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/610746">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=ENSG00000175283;t=ENST00000372586" 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=22845" 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=610746" 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=ENSG00000175283;t=ENST00000372586" 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_014908" 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_014908" 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=610746" 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=15525&isoform_id=15525_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/DOLK" 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/7662482,20140913,23272297,37182637,119608255,194390380,929654251,957950865,957950868" 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/Q9UPQ8" 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=22845" 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=ENSG00000175283;t=ENST00000372586" 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=DOLK" 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=DOLK" 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+22845" 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/DOLK" 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:22845" 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/22845" 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=chr9&hgg_gene=ENST00000372586.4&hgg_start=128945530&hgg_end=128947603&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
|
<span class="panel-title">
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<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:23406" 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/dolk" 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=610746[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=610746[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/DOLK/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000175283" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.gwascentral.org/search?q=DOLK" 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=DOLK" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=DOLK&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/PA162384054" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
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<div style="display: table-cell;">Animal Models</div>
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</div>
|
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</a>
|
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</span>
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</span>
|
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/gene/HGNC:23406" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0034141.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:2677836" 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/DOLK#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:2677836" 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/22845/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=22845" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00044233;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-070410-59" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
|
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</div>
|
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
|
<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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<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:22845" 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=DOLK&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
|
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
|
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<a id="number" class="mim-anchor"></a>
|
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<div class="text-right">
|
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 718712005<br />
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">ICD+</a>
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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>
|
|
610746
|
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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>
|
|
<span class="mim-font">
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DOLICHOL KINASE; DOLK
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</span>
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</h3>
|
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</div>
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<div>
|
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<br />
|
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</div>
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<div>
|
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<a id="alternativeTitles" class="mim-anchor"></a>
|
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<div>
|
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<p>
|
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<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
DOLICHOL KINASE 1; DK1<br />
|
|
SEC59, YEAST, HOMOLOG OF; SEC59<br />
|
|
KIAA1094<br />
|
|
TRANSMEMBRANE PROTEIN 15, FORMERLY; TMEM15, FORMERLY
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
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<div>
|
|
<br />
|
|
</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=DOLK" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">DOLK</a></em></strong>
|
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</span>
|
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</p>
|
|
</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/9/559?start=-3&limit=10&highlight=559">9q34.11</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr9:128945530-128947603&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'})">9:128,945,530-128,947,603</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
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|
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|
|
</span>
|
|
</p>
|
|
</div>
|
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
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<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">
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PheneGene Graphics <span class="caret"></span>
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<p>Dolichyl monophosphate is an essential glycosyl carrier lipid for C- and O-mannosylation and N-glycosylation of proteins and for biosynthesis of glycosyl phosphatidylinositol anchors in endoplasmic reticulum (ER). DOLK catalyzes CTP-mediated phosphorylation of dolichol, the terminal step in de novo dolichyl monophosphate biosynthesis (<a href="#1" class="mim-tip-reference" title="Fernandez, F., Shridas, P., Jiang, S., Aebi, M., Waechter, C. J. <strong>Expression and characterization of a human cDNA that complements the temperature-sensitive defect in dolichol kinase activity in the yeast sec59-1 mutant: the enzymatic phosphorylation of dolichol and diacylglycerol are catalyzed by separate CTP-mediated kinase activities in Saccharomyces cerevisiae.</strong> Glycobiology 12: 555-562, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12213788/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12213788</a>] [<a href="https://doi.org/10.1093/glycob/cwf068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12213788">Fernandez et al., 2002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12213788" 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 sequencing clones obtained from a size-fractionated adult brain cDNA library, <a href="#3" class="mim-tip-reference" title="Kikuno, R., Nagase, T., Ishikawa, K., Hirosawa, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O. <strong>Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.</strong> DNA Res. 6: 197-205, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10470851/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10470851</a>] [<a href="https://doi.org/10.1093/dnares/6.3.197" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10470851">Kikuno et al. (1999)</a> cloned DOLK, which they designated KIAA1094. The deduced protein contains 538 amino acids. RT-PCR ELISA detected low to moderate expression in all adult and fetal tissues examined, with highest expression in liver. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10470851" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Fernandez, F., Shridas, P., Jiang, S., Aebi, M., Waechter, C. J. <strong>Expression and characterization of a human cDNA that complements the temperature-sensitive defect in dolichol kinase activity in the yeast sec59-1 mutant: the enzymatic phosphorylation of dolichol and diacylglycerol are catalyzed by separate CTP-mediated kinase activities in Saccharomyces cerevisiae.</strong> Glycobiology 12: 555-562, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12213788/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12213788</a>] [<a href="https://doi.org/10.1093/glycob/cwf068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12213788">Fernandez et al. (2002)</a> determined that the 538-amino acid DK1 protein has a predicted molecular mass of 59.3 kD. It has 13 transmembrane (TM) domains and shares 30% amino acid identity with yeast Sec59. DK1 expressed in insect cells had an apparent molecular mass of 59 to 60 kD by SDS-PAGE. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12213788" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using immunofluorescence localization of tagged DK1, <a href="#6" class="mim-tip-reference" title="Shridas, P., Waechter, C. J. <strong>Human dolichol kinase, a polytopic endoplasmic reticulum membrane protein with a cytoplasmically oriented CTP-binding site.</strong> J. Biol. Chem. 281: 31696-31704, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16923818/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16923818</a>] [<a href="https://doi.org/10.1074/jbc.M604087200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16923818">Shridas and Waechter (2006)</a> showed that the N terminus of DK1 is on the luminal side of the ER and the C terminus is cytoplasmic. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16923818" 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="Lefeber, D. J., de Brouwer, A. P. M., Morava, E., Riemersma, M., Schuurs-Hoeijmakers, J. H. M., Absmanner, B., Verrijp, K., van den Akker, W. M. R., Huijben, K., Steenbergen, G., van Reeuwijk, J., Jozwiak, A., and 10 others. <strong>Autosomal recessive dilated cardiomyopathy due to DOLK mutations results from abnormal dystroglycan O-mannosylation.</strong> PLoS Genet. 7: e1002427, 2011. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22242004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22242004</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22242004[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1371/journal.pgen.1002427" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22242004">Lefeber et al. (2011)</a> observed highest expression levels of DOLK mRNA in fetal and adult brain, followed by fetal skeletal muscle and heart and adult heart tissue. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22242004" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#1" class="mim-tip-reference" title="Fernandez, F., Shridas, P., Jiang, S., Aebi, M., Waechter, C. J. <strong>Expression and characterization of a human cDNA that complements the temperature-sensitive defect in dolichol kinase activity in the yeast sec59-1 mutant: the enzymatic phosphorylation of dolichol and diacylglycerol are catalyzed by separate CTP-mediated kinase activities in Saccharomyces cerevisiae.</strong> Glycobiology 12: 555-562, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12213788/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12213788</a>] [<a href="https://doi.org/10.1093/glycob/cwf068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12213788">Fernandez et al. (2002)</a> found that overexpression of DK1 complemented the growth deficiency and hypoglycosylation phenotypes of Sec59-deficient yeast. Overexpression of DK1 in Sec59-deficient yeast increased the cellular pool of dolichol phosphate. Crude microsomes from DK1-transfected insect cells showed a 15-fold increase in DK activity compared with controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12213788" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using site-directed mutagenesis, <a href="#6" class="mim-tip-reference" title="Shridas, P., Waechter, C. J. <strong>Human dolichol kinase, a polytopic endoplasmic reticulum membrane protein with a cytoplasmically oriented CTP-binding site.</strong> J. Biol. Chem. 281: 31696-31704, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16923818/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16923818</a>] [<a href="https://doi.org/10.1074/jbc.M604087200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16923818">Shridas and Waechter (2006)</a> showed that asp451, thr472, and the combination of lys470 and lys471, all of which are located in a conserved cytoplasmic motif between TM11 and TM12, were critical for DK1 kinase activity. Mutation of lys470, lys471, and thr472 altered the affinity of DK1 for CTP, but not dolichol. Mutation of gly443 within TM11 also abolished DK1 activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16923818" 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 radiation hybrid analysis, <a href="#3" class="mim-tip-reference" title="Kikuno, R., Nagase, T., Ishikawa, K., Hirosawa, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O. <strong>Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.</strong> DNA Res. 6: 197-205, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10470851/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10470851</a>] [<a href="https://doi.org/10.1093/dnares/6.3.197" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10470851">Kikuno et al. (1999)</a> mapped the DOLK gene to chromosome 9. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10470851" 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="Kranz, C., Jungeblut, C., Denecke, J., Erlekotte, A., Sohlbach, C., Debus, V., Kehl, H. G., Harms, E., Reith, A., Reichel, S., Grobe, H., Hammersen, G., Schwarzer, U., Marquardt, T. <strong>A defect in dolichol phosphate biosynthesis causes a new inherited disorder with death in early infancy.</strong> Am. J. Hum. Genet. 80: 433-440, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17273964/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17273964</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17273964[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/512130" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17273964">Kranz et al. (2007)</a> described 2 consanguineous families, one German and one Turkish, each with 2 infants with congenital disorder of glycosylation type Im (CDG1M; <a href="/entry/610768">610768</a>), previously designated dolichol kinase deficiency. In each patient they found homozygosity for 1 of 2 mutations in the DOLK gene (<a href="#0001">610746.0001</a>; <a href="#0002">610746.0002</a>). Affected individuals presented with a severe phenotype, including muscular hypotonia and dilated cardiomyopathy (CMD), and died in early infancy. Dolichol phosphate is involved in several glycosylation reactions, such as N-glycosylation, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, and C- and O-mannosylation. All 4 patients reported by <a href="#4" class="mim-tip-reference" title="Kranz, C., Jungeblut, C., Denecke, J., Erlekotte, A., Sohlbach, C., Debus, V., Kehl, H. G., Harms, E., Reith, A., Reichel, S., Grobe, H., Hammersen, G., Schwarzer, U., Marquardt, T. <strong>A defect in dolichol phosphate biosynthesis causes a new inherited disorder with death in early infancy.</strong> Am. J. Hum. Genet. 80: 433-440, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17273964/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17273964</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17273964[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/512130" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17273964">Kranz et al. (2007)</a> showed a remarkable loss of oligosaccharide structures on serum transferrin, as shown by isoelectric focusing (IEF) and immunoprecipitation of the protein, thus implicating a disorder affecting N-glycosylation. This finding prompted <a href="#4" class="mim-tip-reference" title="Kranz, C., Jungeblut, C., Denecke, J., Erlekotte, A., Sohlbach, C., Debus, V., Kehl, H. G., Harms, E., Reith, A., Reichel, S., Grobe, H., Hammersen, G., Schwarzer, U., Marquardt, T. <strong>A defect in dolichol phosphate biosynthesis causes a new inherited disorder with death in early infancy.</strong> Am. J. Hum. Genet. 80: 433-440, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17273964/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17273964</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17273964[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/512130" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17273964">Kranz et al. (2007)</a> to analyze the biosynthetic pathway of dolichol phosphate. <a href="#4" class="mim-tip-reference" title="Kranz, C., Jungeblut, C., Denecke, J., Erlekotte, A., Sohlbach, C., Debus, V., Kehl, H. G., Harms, E., Reith, A., Reichel, S., Grobe, H., Hammersen, G., Schwarzer, U., Marquardt, T. <strong>A defect in dolichol phosphate biosynthesis causes a new inherited disorder with death in early infancy.</strong> Am. J. Hum. Genet. 80: 433-440, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17273964/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17273964</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17273964[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/512130" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17273964">Kranz et al. (2007)</a> stated that this was the first defect in humans that affects the biosynthesis of dolichol phosphate by the disturbance of the final phosphorylation step. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17273964" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected children from 4 unrelated consanguineous families with dolichol kinase deficiency and CMD mapping to chromosome 9q33.1-q34.11, <a href="#5" class="mim-tip-reference" title="Lefeber, D. J., de Brouwer, A. P. M., Morava, E., Riemersma, M., Schuurs-Hoeijmakers, J. H. M., Absmanner, B., Verrijp, K., van den Akker, W. M. R., Huijben, K., Steenbergen, G., van Reeuwijk, J., Jozwiak, A., and 10 others. <strong>Autosomal recessive dilated cardiomyopathy due to DOLK mutations results from abnormal dystroglycan O-mannosylation.</strong> PLoS Genet. 7: e1002427, 2011. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22242004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22242004</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22242004[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1371/journal.pgen.1002427" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22242004">Lefeber et al. (2011)</a> identified homozygosity for 3 missense mutations in the DOLK gene (<a href="#0003">610746.0003</a>-<a href="#0005">610746.0005</a>). Unlike the patients described previously by <a href="#4" class="mim-tip-reference" title="Kranz, C., Jungeblut, C., Denecke, J., Erlekotte, A., Sohlbach, C., Debus, V., Kehl, H. G., Harms, E., Reith, A., Reichel, S., Grobe, H., Hammersen, G., Schwarzer, U., Marquardt, T. <strong>A defect in dolichol phosphate biosynthesis causes a new inherited disorder with death in early infancy.</strong> Am. J. Hum. Genet. 80: 433-440, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17273964/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17273964</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17273964[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/512130" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17273964">Kranz et al. (2007)</a>, who died in early infancy with a severe congenital multisystem phenotype, these children presented primarily with nonsyndromic dilated cardiomyopathy at 5 to 13 years of age, and additional clinical symptoms in some of the patients, including ichthyosiform dermatitis, failure to thrive, and neurologic involvement, were mild. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17273964+22242004" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>6 Selected Examples</a>):</strong>
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<a href="/allelicVariants/610746" class="btn btn-default" role="button"> Table View </a>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=610746[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<strong>.0001 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Im</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">rs137853109 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853109;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=rs137853109" 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=rs137853109" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 2 affected first cousins in a consanguineous German family, <a href="#4" class="mim-tip-reference" title="Kranz, C., Jungeblut, C., Denecke, J., Erlekotte, A., Sohlbach, C., Debus, V., Kehl, H. G., Harms, E., Reith, A., Reichel, S., Grobe, H., Hammersen, G., Schwarzer, U., Marquardt, T. <strong>A defect in dolichol phosphate biosynthesis causes a new inherited disorder with death in early infancy.</strong> Am. J. Hum. Genet. 80: 433-440, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17273964/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17273964</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17273964[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/512130" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17273964">Kranz et al. (2007)</a> demonstrated that congenital disorder of glycosylation type Im (<a href="/entry/610768">610768</a>) was caused by homozygosity for a 295T-A transversion in the DOLK gene, resulting in a cys99-to-ser (C99S) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17273964" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0002 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Im</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> rs137853110 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853110;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/rs137853110?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=rs137853110" 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=rs137853110" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 2 affected sibs in a consanguineous Turkish family, <a href="#4" class="mim-tip-reference" title="Kranz, C., Jungeblut, C., Denecke, J., Erlekotte, A., Sohlbach, C., Debus, V., Kehl, H. G., Harms, E., Reith, A., Reichel, S., Grobe, H., Hammersen, G., Schwarzer, U., Marquardt, T. <strong>A defect in dolichol phosphate biosynthesis causes a new inherited disorder with death in early infancy.</strong> Am. J. Hum. Genet. 80: 433-440, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17273964/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17273964</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17273964[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/512130" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17273964">Kranz et al. (2007)</a> demonstrated that congenital disorder of glycosylation type Im (CDG1M; <a href="/entry/610768">610768</a>) was caused by homozygosity for a 1322A-C transversion in the DOLK gene, resulting in a tyr441-to-ser (Y441S) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17273964" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Im</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">rs387907030 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387907030;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=rs387907030" 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=rs387907030" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In affected children from 2 consanguineous Israeli Druze families with congenital disorder of glycosylation type Im (CDG1M; <a href="/entry/610768">610768</a>), <a href="#5" class="mim-tip-reference" title="Lefeber, D. J., de Brouwer, A. P. M., Morava, E., Riemersma, M., Schuurs-Hoeijmakers, J. H. M., Absmanner, B., Verrijp, K., van den Akker, W. M. R., Huijben, K., Steenbergen, G., van Reeuwijk, J., Jozwiak, A., and 10 others. <strong>Autosomal recessive dilated cardiomyopathy due to DOLK mutations results from abnormal dystroglycan O-mannosylation.</strong> PLoS Genet. 7: e1002427, 2011. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22242004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22242004</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22242004[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1371/journal.pgen.1002427" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22242004">Lefeber et al. (2011)</a> identified homozygosity for a 1222C-G transversion in the DOLK gene, resulting in a his408-to-asp (H408D) substitution at a highly conserved residue. The mutation was not found in more than 1,000 Caucasian controls or in the 1000 Genomes Project. Although the families resided in 2 different villages in northern Israel and were believed to be unrelated, the presence of an identical 5-Mb haplotype and mutation suggested a founder event among these Druze kindreds. Functional analysis in temperature-sensitive underglycosylated sec59 yeast cells demonstrated that the mutant protein failed to restore glycosylation to the same extent as wildtype. Cardiac tissue from a patient's explanted heart showed reduced O-mannosylation of alpha dystroglycan (<a href="/entry/128239">128239</a>) with concomitant functional loss of its laminin (see <a href="/entry/150320">150320</a>)-binding capacity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22242004" 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 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Im</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">rs1564545929 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1564545929;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=rs1564545929" 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=rs1564545929" 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=RCV000023836" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023836" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023836</a>
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<p>In 3 affected sibs from a consanguineous Bedouin family of northern Israel with congenital disorder of glycosylation type Im (CDG1M; <a href="/entry/610768">610768</a>), <a href="#5" class="mim-tip-reference" title="Lefeber, D. J., de Brouwer, A. P. M., Morava, E., Riemersma, M., Schuurs-Hoeijmakers, J. H. M., Absmanner, B., Verrijp, K., van den Akker, W. M. R., Huijben, K., Steenbergen, G., van Reeuwijk, J., Jozwiak, A., and 10 others. <strong>Autosomal recessive dilated cardiomyopathy due to DOLK mutations results from abnormal dystroglycan O-mannosylation.</strong> PLoS Genet. 7: e1002427, 2011. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22242004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22242004</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22242004[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1371/journal.pgen.1002427" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22242004">Lefeber et al. (2011)</a> identified homozygosity for a 912G-T transversion in the DOLK gene, resulting in a trp304-to-cys (W304C) substitution at a highly conserved residue. The mutation was not found in more than 1,000 Caucasian controls or in the 1000 Genomes Project. Functional analysis in temperature-sensitive underglycosylated sec59 yeast cells demonstrated that the mutant protein failed to restore glycosylation to the same extent as wildtype. The 13-year-old girl had asymptomatic dilated cardiomyopathy and her 2 asymptomatic younger brothers showed minimal evidence of CMD on echocardiography; all 3 sibs had ichthyosiform dermatitis. Their older brother had died at 9 years of age from end-stage CMD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22242004" 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">rs1564546510 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1564546510;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=rs1564546510" 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=rs1564546510" 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=RCV000023837" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023837" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023837</a>
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<p>In an 11-year-old Indian girl with congenital disorder of glycosylation type Im (CDG1M; <a href="/entry/610768">610768</a>), who died while awaiting cardiac transplant for dilated cardiomyopathy, <a href="#5" class="mim-tip-reference" title="Lefeber, D. J., de Brouwer, A. P. M., Morava, E., Riemersma, M., Schuurs-Hoeijmakers, J. H. M., Absmanner, B., Verrijp, K., van den Akker, W. M. R., Huijben, K., Steenbergen, G., van Reeuwijk, J., Jozwiak, A., and 10 others. <strong>Autosomal recessive dilated cardiomyopathy due to DOLK mutations results from abnormal dystroglycan O-mannosylation.</strong> PLoS Genet. 7: e1002427, 2011. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22242004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22242004</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22242004[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1371/journal.pgen.1002427" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22242004">Lefeber et al. (2011)</a> identified homozygosity for a 3G-A transition in the DOLK gene, resulting in a met1-to-ile (M1I) substitution at the highly conserved initiator residue. Her affected younger brother, who had mild developmental delay and CMD but normal cardiac function, was also homozygous for the mutation, which was not found in more than 1,000 Caucasian controls or in the 1000 Genomes Project. Functional analysis in temperature-sensitive underglycosylated sec59 yeast cells demonstrated that the mutant protein failed to restore glycosylation to the same extent as wildtype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22242004" 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">rs587777137 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777137;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=rs587777137" 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=rs587777137" 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=RCV000087064 OR RCV001818254 OR RCV002433594" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000087064, RCV001818254, RCV002433594" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000087064...</a>
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<p>In 2 sibs, born of consanguineous Syrian Turkish parents, with congenital disorder of glycosylation type Im (CDG1M; <a href="/entry/610768">610768</a>), <a href="#2" class="mim-tip-reference" title="Helander, A., Stodberg, T., Jaeken, J., Matthijs, G., Eriksson, M., Eggertsen, G. <strong>Dolichol kinase deficiency (DOLK-CDG) with a purely neurological presentation caused by a novel mutation.</strong> Molec. Genet. Metab. 110: 342-344, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23890587/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23890587</a>] [<a href="https://doi.org/10.1016/j.ymgme.2013.07.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23890587">Helander et al. (2013)</a> identified a homozygous c.2T-C transition in the DOLK gene, resulting in a change in the initiation methionine triplet. The authors referred to the mutation as M1?. The patients presented at age 4 months with severe intractable seizures and hypsarrhythmia, consistent with a clinical diagnosis of West syndrome (see <a href="/entry/308350">308350</a>). Both had normal early development before the onset of seizures, but thereafter showed delayed psychomotor development with lack of speech. The seizures eventually remitted later in childhood in both patients after intense therapy. Neither patient had cardiac involvement. Serum transferrin analysis showed a CDG type 1 pattern, and lipid-linked oligosaccharides were normal, suggesting an early defect in glycan assembly. <a href="#2" class="mim-tip-reference" title="Helander, A., Stodberg, T., Jaeken, J., Matthijs, G., Eriksson, M., Eggertsen, G. <strong>Dolichol kinase deficiency (DOLK-CDG) with a purely neurological presentation caused by a novel mutation.</strong> Molec. Genet. Metab. 110: 342-344, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23890587/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23890587</a>] [<a href="https://doi.org/10.1016/j.ymgme.2013.07.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23890587">Helander et al. (2013)</a> emphasized the purely neurologic presentation in these patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23890587" 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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Fernandez, F., Shridas, P., Jiang, S., Aebi, M., Waechter, C. J.
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<strong>Expression and characterization of a human cDNA that complements the temperature-sensitive defect in dolichol kinase activity in the yeast sec59-1 mutant: the enzymatic phosphorylation of dolichol and diacylglycerol are catalyzed by separate CTP-mediated kinase activities in Saccharomyces cerevisiae.</strong>
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Glycobiology 12: 555-562, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12213788/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12213788</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12213788" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Helander, A., Stodberg, T., Jaeken, J., Matthijs, G., Eriksson, M., Eggertsen, G.
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<strong>Dolichol kinase deficiency (DOLK-CDG) with a purely neurological presentation caused by a novel mutation.</strong>
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Molec. Genet. Metab. 110: 342-344, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23890587/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23890587</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23890587" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Kikuno, R., Nagase, T., Ishikawa, K., Hirosawa, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O.
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<strong>Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.</strong>
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DNA Res. 6: 197-205, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10470851/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10470851</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10470851" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Kranz, C., Jungeblut, C., Denecke, J., Erlekotte, A., Sohlbach, C., Debus, V., Kehl, H. G., Harms, E., Reith, A., Reichel, S., Grobe, H., Hammersen, G., Schwarzer, U., Marquardt, T.
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<strong>A defect in dolichol phosphate biosynthesis causes a new inherited disorder with death in early infancy.</strong>
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Am. J. Hum. Genet. 80: 433-440, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17273964/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17273964</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17273964[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17273964" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Lefeber, D. J., de Brouwer, A. P. M., Morava, E., Riemersma, M., Schuurs-Hoeijmakers, J. H. M., Absmanner, B., Verrijp, K., van den Akker, W. M. R., Huijben, K., Steenbergen, G., van Reeuwijk, J., Jozwiak, A., and 10 others.
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<strong>Autosomal recessive dilated cardiomyopathy due to DOLK mutations results from abnormal dystroglycan O-mannosylation.</strong>
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PLoS Genet. 7: e1002427, 2011. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22242004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22242004</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22242004[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22242004" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Shridas, P., Waechter, C. J.
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<strong>Human dolichol kinase, a polytopic endoplasmic reticulum membrane protein with a cytoplasmically oriented CTP-binding site.</strong>
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J. Biol. Chem. 281: 31696-31704, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16923818/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16923818</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16923818" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 2/12/2014
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</span>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 2/16/2012<br>Victor A. McKusick - updated : 2/20/2007
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</span>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Patricia A. Hartz : 2/6/2007
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 03/27/2017
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</span>
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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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alopez : 02/21/2014<br>mcolton : 2/18/2014<br>ckniffin : 2/12/2014<br>carol : 2/24/2012<br>terry : 2/16/2012<br>mgross : 1/17/2012<br>terry : 1/14/2011<br>alopez : 2/22/2007<br>carol : 2/20/2007<br>mgross : 2/6/2007
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<h3>
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<span class="mim-font">
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<strong>*</strong> 610746
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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DOLICHOL KINASE; DOLK
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</span>
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</h3>
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</div>
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<div>
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<br />
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<div >
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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DOLICHOL KINASE 1; DK1<br />
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SEC59, YEAST, HOMOLOG OF; SEC59<br />
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KIAA1094<br />
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TRANSMEMBRANE PROTEIN 15, FORMERLY; TMEM15, FORMERLY
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</span>
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</h4>
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</div>
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<br />
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: DOLK</em></strong>
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 718712005;
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</span>
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</p>
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<br />
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 9q34.11
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Genomic coordinates <span class="small">(GRCh38)</span> : 9:128,945,530-128,947,603 </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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9q34.11
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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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Congenital disorder of glycosylation, type Im
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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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610768
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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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</table>
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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>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Dolichyl monophosphate is an essential glycosyl carrier lipid for C- and O-mannosylation and N-glycosylation of proteins and for biosynthesis of glycosyl phosphatidylinositol anchors in endoplasmic reticulum (ER). DOLK catalyzes CTP-mediated phosphorylation of dolichol, the terminal step in de novo dolichyl monophosphate biosynthesis (Fernandez et al., 2002). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By sequencing clones obtained from a size-fractionated adult brain cDNA library, Kikuno et al. (1999) cloned DOLK, which they designated KIAA1094. The deduced protein contains 538 amino acids. RT-PCR ELISA detected low to moderate expression in all adult and fetal tissues examined, with highest expression in liver. </p><p>Fernandez et al. (2002) determined that the 538-amino acid DK1 protein has a predicted molecular mass of 59.3 kD. It has 13 transmembrane (TM) domains and shares 30% amino acid identity with yeast Sec59. DK1 expressed in insect cells had an apparent molecular mass of 59 to 60 kD by SDS-PAGE. </p><p>Using immunofluorescence localization of tagged DK1, Shridas and Waechter (2006) showed that the N terminus of DK1 is on the luminal side of the ER and the C terminus is cytoplasmic. </p><p>Lefeber et al. (2011) observed highest expression levels of DOLK mRNA in fetal and adult brain, followed by fetal skeletal muscle and heart and adult heart tissue. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Fernandez et al. (2002) found that overexpression of DK1 complemented the growth deficiency and hypoglycosylation phenotypes of Sec59-deficient yeast. Overexpression of DK1 in Sec59-deficient yeast increased the cellular pool of dolichol phosphate. Crude microsomes from DK1-transfected insect cells showed a 15-fold increase in DK activity compared with controls. </p><p>Using site-directed mutagenesis, Shridas and Waechter (2006) showed that asp451, thr472, and the combination of lys470 and lys471, all of which are located in a conserved cytoplasmic motif between TM11 and TM12, were critical for DK1 kinase activity. Mutation of lys470, lys471, and thr472 altered the affinity of DK1 for CTP, but not dolichol. Mutation of gly443 within TM11 also abolished DK1 activity. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By radiation hybrid analysis, Kikuno et al. (1999) mapped the DOLK gene to chromosome 9. </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>Kranz et al. (2007) described 2 consanguineous families, one German and one Turkish, each with 2 infants with congenital disorder of glycosylation type Im (CDG1M; 610768), previously designated dolichol kinase deficiency. In each patient they found homozygosity for 1 of 2 mutations in the DOLK gene (610746.0001; 610746.0002). Affected individuals presented with a severe phenotype, including muscular hypotonia and dilated cardiomyopathy (CMD), and died in early infancy. Dolichol phosphate is involved in several glycosylation reactions, such as N-glycosylation, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, and C- and O-mannosylation. All 4 patients reported by Kranz et al. (2007) showed a remarkable loss of oligosaccharide structures on serum transferrin, as shown by isoelectric focusing (IEF) and immunoprecipitation of the protein, thus implicating a disorder affecting N-glycosylation. This finding prompted Kranz et al. (2007) to analyze the biosynthetic pathway of dolichol phosphate. Kranz et al. (2007) stated that this was the first defect in humans that affects the biosynthesis of dolichol phosphate by the disturbance of the final phosphorylation step. </p><p>In affected children from 4 unrelated consanguineous families with dolichol kinase deficiency and CMD mapping to chromosome 9q33.1-q34.11, Lefeber et al. (2011) identified homozygosity for 3 missense mutations in the DOLK gene (610746.0003-610746.0005). Unlike the patients described previously by Kranz et al. (2007), who died in early infancy with a severe congenital multisystem phenotype, these children presented primarily with nonsyndromic dilated cardiomyopathy at 5 to 13 years of age, and additional clinical symptoms in some of the patients, including ichthyosiform dermatitis, failure to thrive, and neurologic involvement, were mild. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>ALLELIC VARIANTS</strong>
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</span>
|
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<strong>6 Selected Examples):</strong>
|
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</span>
|
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</h4>
|
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<div>
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<p />
|
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0001 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Im</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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DOLK, CYS99SER
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<br />
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|
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SNP: rs137853109,
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ClinVar: RCV000001190
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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 2 affected first cousins in a consanguineous German family, Kranz et al. (2007) demonstrated that congenital disorder of glycosylation type Im (610768) was caused by homozygosity for a 295T-A transversion in the DOLK gene, resulting in a cys99-to-ser (C99S) substitution. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Im</strong>
|
|
</span>
|
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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DOLK, TYR441SER
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<br />
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SNP: rs137853110,
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gnomAD: rs137853110,
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ClinVar: RCV000001191
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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|
<p>In 2 affected sibs in a consanguineous Turkish family, Kranz et al. (2007) demonstrated that congenital disorder of glycosylation type Im (CDG1M; 610768) was caused by homozygosity for a 1322A-C transversion in the DOLK gene, resulting in a tyr441-to-ser (Y441S) substitution. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Im</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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DOLK, HIS408ASP
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<br />
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SNP: rs387907030,
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ClinVar: RCV000023835
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In affected children from 2 consanguineous Israeli Druze families with congenital disorder of glycosylation type Im (CDG1M; 610768), Lefeber et al. (2011) identified homozygosity for a 1222C-G transversion in the DOLK gene, resulting in a his408-to-asp (H408D) substitution at a highly conserved residue. The mutation was not found in more than 1,000 Caucasian controls or in the 1000 Genomes Project. Although the families resided in 2 different villages in northern Israel and were believed to be unrelated, the presence of an identical 5-Mb haplotype and mutation suggested a founder event among these Druze kindreds. Functional analysis in temperature-sensitive underglycosylated sec59 yeast cells demonstrated that the mutant protein failed to restore glycosylation to the same extent as wildtype. Cardiac tissue from a patient's explanted heart showed reduced O-mannosylation of alpha dystroglycan (128239) with concomitant functional loss of its laminin (see 150320)-binding capacity. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Im</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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DOLK, TRP304CYS
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<br />
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SNP: rs1564545929,
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ClinVar: RCV000023836
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 3 affected sibs from a consanguineous Bedouin family of northern Israel with congenital disorder of glycosylation type Im (CDG1M; 610768), Lefeber et al. (2011) identified homozygosity for a 912G-T transversion in the DOLK gene, resulting in a trp304-to-cys (W304C) substitution at a highly conserved residue. The mutation was not found in more than 1,000 Caucasian controls or in the 1000 Genomes Project. Functional analysis in temperature-sensitive underglycosylated sec59 yeast cells demonstrated that the mutant protein failed to restore glycosylation to the same extent as wildtype. The 13-year-old girl had asymptomatic dilated cardiomyopathy and her 2 asymptomatic younger brothers showed minimal evidence of CMD on echocardiography; all 3 sibs had ichthyosiform dermatitis. Their older brother had died at 9 years of age from end-stage CMD. </p>
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</span>
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</div>
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<h4>
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<span class="mim-font">
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<strong>.0005 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Im</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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DOLK, MET1ILE
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<br />
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SNP: rs1564546510,
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ClinVar: RCV000023837
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</span>
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<span class="mim-text-font">
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<p>In an 11-year-old Indian girl with congenital disorder of glycosylation type Im (CDG1M; 610768), who died while awaiting cardiac transplant for dilated cardiomyopathy, Lefeber et al. (2011) identified homozygosity for a 3G-A transition in the DOLK gene, resulting in a met1-to-ile (M1I) substitution at the highly conserved initiator residue. Her affected younger brother, who had mild developmental delay and CMD but normal cardiac function, was also homozygous for the mutation, which was not found in more than 1,000 Caucasian controls or in the 1000 Genomes Project. Functional analysis in temperature-sensitive underglycosylated sec59 yeast cells demonstrated that the mutant protein failed to restore glycosylation to the same extent as wildtype. </p>
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<h4>
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<span class="mim-font">
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<strong>.0006 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Im</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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DOLK, MET1?
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<br />
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SNP: rs587777137,
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ClinVar: RCV000087064, RCV001818254, RCV002433594
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<span class="mim-text-font">
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<p>In 2 sibs, born of consanguineous Syrian Turkish parents, with congenital disorder of glycosylation type Im (CDG1M; 610768), Helander et al. (2013) identified a homozygous c.2T-C transition in the DOLK gene, resulting in a change in the initiation methionine triplet. The authors referred to the mutation as M1?. The patients presented at age 4 months with severe intractable seizures and hypsarrhythmia, consistent with a clinical diagnosis of West syndrome (see 308350). Both had normal early development before the onset of seizures, but thereafter showed delayed psychomotor development with lack of speech. The seizures eventually remitted later in childhood in both patients after intense therapy. Neither patient had cardiac involvement. Serum transferrin analysis showed a CDG type 1 pattern, and lipid-linked oligosaccharides were normal, suggesting an early defect in glycan assembly. Helander et al. (2013) emphasized the purely neurologic presentation in these patients. </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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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Fernandez, F., Shridas, P., Jiang, S., Aebi, M., Waechter, C. J.
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<strong>Expression and characterization of a human cDNA that complements the temperature-sensitive defect in dolichol kinase activity in the yeast sec59-1 mutant: the enzymatic phosphorylation of dolichol and diacylglycerol are catalyzed by separate CTP-mediated kinase activities in Saccharomyces cerevisiae.</strong>
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Glycobiology 12: 555-562, 2002.
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[PubMed: 12213788]
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[Full Text: https://doi.org/10.1093/glycob/cwf068]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Helander, A., Stodberg, T., Jaeken, J., Matthijs, G., Eriksson, M., Eggertsen, G.
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<strong>Dolichol kinase deficiency (DOLK-CDG) with a purely neurological presentation caused by a novel mutation.</strong>
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Molec. Genet. Metab. 110: 342-344, 2013.
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[PubMed: 23890587]
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[Full Text: https://doi.org/10.1016/j.ymgme.2013.07.002]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Kikuno, R., Nagase, T., Ishikawa, K., Hirosawa, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O.
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<strong>Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.</strong>
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DNA Res. 6: 197-205, 1999.
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[PubMed: 10470851]
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[Full Text: https://doi.org/10.1093/dnares/6.3.197]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Kranz, C., Jungeblut, C., Denecke, J., Erlekotte, A., Sohlbach, C., Debus, V., Kehl, H. G., Harms, E., Reith, A., Reichel, S., Grobe, H., Hammersen, G., Schwarzer, U., Marquardt, T.
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<strong>A defect in dolichol phosphate biosynthesis causes a new inherited disorder with death in early infancy.</strong>
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Am. J. Hum. Genet. 80: 433-440, 2007.
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[PubMed: 17273964]
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[Full Text: https://doi.org/10.1086/512130]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Lefeber, D. J., de Brouwer, A. P. M., Morava, E., Riemersma, M., Schuurs-Hoeijmakers, J. H. M., Absmanner, B., Verrijp, K., van den Akker, W. M. R., Huijben, K., Steenbergen, G., van Reeuwijk, J., Jozwiak, A., and 10 others.
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<strong>Autosomal recessive dilated cardiomyopathy due to DOLK mutations results from abnormal dystroglycan O-mannosylation.</strong>
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PLoS Genet. 7: e1002427, 2011. Note: Electronic Article.
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[PubMed: 22242004]
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[Full Text: https://doi.org/10.1371/journal.pgen.1002427]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Shridas, P., Waechter, C. J.
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<strong>Human dolichol kinase, a polytopic endoplasmic reticulum membrane protein with a cytoplasmically oriented CTP-binding site.</strong>
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J. Biol. Chem. 281: 31696-31704, 2006.
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[PubMed: 16923818]
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[Full Text: https://doi.org/10.1074/jbc.M604087200]
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</p>
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</li>
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</ol>
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<div>
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<br />
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</div>
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<span class="text-nowrap mim-text-font">
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Contributors:
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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 : 2/12/2014<br>Marla J. F. O'Neill - updated : 2/16/2012<br>Victor A. McKusick - updated : 2/20/2007
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</span>
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<span class="mim-text-font">
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Patricia A. Hartz : 2/6/2007
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carol : 03/27/2017<br>alopez : 02/21/2014<br>mcolton : 2/18/2014<br>ckniffin : 2/12/2014<br>carol : 2/24/2012<br>terry : 2/16/2012<br>mgross : 1/17/2012<br>terry : 1/14/2011<br>alopez : 2/22/2007<br>carol : 2/20/2007<br>mgross : 2/6/2007
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