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<title>
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Entry
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- *617538 - ELONGATION FACTOR-LIKE GTPase 1; EFL1
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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="row">
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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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<a href="/history"> Search History </a>
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</ul>
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</div>
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</div>
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<div class="autocomplete" id="mimEntrySearchAutocomplete"></div>
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<div class="col-lg-4 col-md-4 col-sm-4 col-xs-4">
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<span class="small">
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</form>
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<p />
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</div>
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<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
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<div id="mimAlertBanner">
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</div>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-2 hidden-sm hidden-xs">
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*617538</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>
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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="#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="#geneFunction">Gene Function</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" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</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/617538">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=ENSG00000140598;t=ENST00000268206" 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=79631" 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=617538" 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=ENSG00000140598;t=ENST00000268206" 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_001040610,NM_001322844,NM_001322845,NM_024580,NR_136410,XM_024450048" 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_024580" 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=617538" 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://www.proteinatlas.org/search/EFL1" 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/10434992,31874828,94966752,94966754,119619493,119619494,119619495,166232397,193786494,221043178,1017207212,1017207214,1370467207,2462545816" 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/Q7Z2Z2" 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=79631" 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=ENSG00000140598;t=ENST00000268206" 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=EFL1" 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=EFL1" 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+79631" 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/EFL1" 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:79631" 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/79631" 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=chr15&hgg_gene=ENST00000268206.12&hgg_start=82130233&hgg_end=82262734&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:25789" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=617538[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=617538[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000140598" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=EFL1" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=EFL1" 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=EFL1" 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=EFL1&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/PA134902221" 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:25789" 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/FBgn0053158.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:2141969" 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/EFL1#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:2141969" 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/79631/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=79631" 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=WBGene00010732;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-130103-6" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
|
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<span class="small">
|
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
|
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</div>
|
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</a>
|
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</span>
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</span>
|
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:79631" 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=EFL1&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
|
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<div class="text-right">
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</div>
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<div>
|
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<span class="h3">
|
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<span class="mim-font mim-tip-hint" title="Gene description">
|
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<span class="text-danger"><strong>*</strong></span>
|
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617538
|
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</span>
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</span>
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</div>
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</div>
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<div>
|
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<a id="preferredTitle" class="mim-anchor"></a>
|
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<h3>
|
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<span class="mim-font">
|
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|
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ELONGATION FACTOR-LIKE GTPase 1; EFL1
|
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</span>
|
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</h3>
|
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</div>
|
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<div>
|
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<br />
|
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</div>
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<div>
|
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<a id="alternativeTitles" class="mim-anchor"></a>
|
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<div>
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<p>
|
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<span class="mim-font">
|
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<em>Alternative titles; symbols</em>
|
|
</span>
|
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</p>
|
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</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
RIBOSOME ASSEMBLY 1 HOMOLOG; RIA1<br />
|
|
ELONGATION FACTOR Tu GTP-BINDING DOMAIN-CONTAINING 1; EFTUD1<br />
|
|
FAM42A
|
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</span>
|
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</h4>
|
|
</div>
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</div>
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<div>
|
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<br />
|
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</div>
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</div>
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<div>
|
|
<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=EFL1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">EFL1</a></em></strong>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/15/452?start=-3&limit=10&highlight=452">15q25.2</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr15:82130233-82262734&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'})">15:82,130,233-82,262,734</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>
|
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</p>
|
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</div>
|
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|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
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|
</th>
|
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<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
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<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/15/452?start=-3&limit=10&highlight=452">
|
|
15q25.2
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Shwachman-Diamond syndrome 2
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/617941"> 617941 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
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<p>EFL1 is a GTPase that acts in concert with SBDS (<a href="/entry/607444">607444</a>) in the cytoplasmic maturation of the 60S ribosomal subunit by catalyzing GTP-dependent removal of the assembly factor EIF6 (<a href="/entry/602912">602912</a>) from the maturing ribosome (<a href="#1" class="mim-tip-reference" title="Finch, A. J., Hilcenko, C., Basse, N., Drynan, L. F., Goyenechea, B., Menne, T. F., Gonzalez Fernandez, A., Simpson, P., D'Santos, C. S., Arends, M. J., Donadieu, J., Bellanne-Chantelot, C., Costanzo, M., Boone, C., McKenzie, A. N., Freund, S. M. V., Warren, A. J. <strong>Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes Shwachman-Diamond syndrome.</strong> Genes Dev. 25: 917-929, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21536732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21536732</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21536732[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/10.1101/gad.623011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21536732">Finch et al., 2011</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21536732" 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 searching for the human ortholog of yeast Efl1, <a href="#1" class="mim-tip-reference" title="Finch, A. J., Hilcenko, C., Basse, N., Drynan, L. F., Goyenechea, B., Menne, T. F., Gonzalez Fernandez, A., Simpson, P., D'Santos, C. S., Arends, M. J., Donadieu, J., Bellanne-Chantelot, C., Costanzo, M., Boone, C., McKenzie, A. N., Freund, S. M. V., Warren, A. J. <strong>Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes Shwachman-Diamond syndrome.</strong> Genes Dev. 25: 917-929, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21536732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21536732</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21536732[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/10.1101/gad.623011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21536732">Finch et al. (2011)</a> identified EFL1. The deduced 1,120-amino acid protein has 5 conserved GTPase motifs, including the GTP-binding G domain. By Western blot analysis of glioma tissues and cell lines, <a href="#5" class="mim-tip-reference" title="Saito, K., Iizuka, Y., Ohta, S., Takahashi, S., Nakamura, K., Saya, H., Yoshida, K., Kawakami, Y., Toda, M. <strong>Functional analysis of a novel glioma antigen, EFTUD1.</strong> Neuro-Oncol. 16: 1618-1629, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25015090/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25015090</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25015090[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/neuonc/nou132" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25015090">Saito et al. (2014)</a> found that EFTUD1 had an apparent molecular mass of 125 kD. Immunohistochemical analysis revealed predominant EFTUD1 expression in the cytoplasm, with little expression in the nucleus. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=25015090+21536732" 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="#3" class="mim-tip-reference" title="Hartz, P. A. <strong>Personal Communication.</strong> Baltimore, Md. June 6, 2017."None>Hartz (2017)</a> mapped the EFL1 gene to chromosome 15q25.2 based on an alignment of the EFL1 sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=AK023181" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">AK023181</a>) with the genomic sequence (GRCh38).</p>
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<p><a href="#1" class="mim-tip-reference" title="Finch, A. J., Hilcenko, C., Basse, N., Drynan, L. F., Goyenechea, B., Menne, T. F., Gonzalez Fernandez, A., Simpson, P., D'Santos, C. S., Arends, M. J., Donadieu, J., Bellanne-Chantelot, C., Costanzo, M., Boone, C., McKenzie, A. N., Freund, S. M. V., Warren, A. J. <strong>Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes Shwachman-Diamond syndrome.</strong> Genes Dev. 25: 917-929, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21536732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21536732</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21536732[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/10.1101/gad.623011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21536732">Finch et al. (2011)</a> showed that GTP and recombinant human SBDS and EFL1 cooperated to trigger release of human EIF6 (<a href="/entry/602912">602912</a>) from pre60S ribosomes isolated from Sbds-deficient mouse livers. EFL1 and SBDS independently and noncooperatively bound to the 60S subunit in vitro. The 60S subunit activated the GTPase activity of EFL1, but SBDS was required to stimulate EIF6 release. Two SBDS mutants with different SDS-associated missense mutations varied in their ability to enhance 60S-dependent GTPase activity of EFL1, but neither triggered EIF6 release. <a href="#1" class="mim-tip-reference" title="Finch, A. J., Hilcenko, C., Basse, N., Drynan, L. F., Goyenechea, B., Menne, T. F., Gonzalez Fernandez, A., Simpson, P., D'Santos, C. S., Arends, M. J., Donadieu, J., Bellanne-Chantelot, C., Costanzo, M., Boone, C., McKenzie, A. N., Freund, S. M. V., Warren, A. J. <strong>Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes Shwachman-Diamond syndrome.</strong> Genes Dev. 25: 917-929, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21536732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21536732</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21536732[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/10.1101/gad.623011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21536732">Finch et al. (2011)</a> concluded that SBDS and EFL1 catalyze translational activation and proposed that SDS is a ribosomopathy caused by uncoupling GTP hydrolysis from EIF6 release. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21536732" 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 quantitative PCR and Western blot analysis, <a href="#5" class="mim-tip-reference" title="Saito, K., Iizuka, Y., Ohta, S., Takahashi, S., Nakamura, K., Saya, H., Yoshida, K., Kawakami, Y., Toda, M. <strong>Functional analysis of a novel glioma antigen, EFTUD1.</strong> Neuro-Oncol. 16: 1618-1629, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25015090/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25015090</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25015090[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/neuonc/nou132" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25015090">Saito et al. (2014)</a> found that expression of EFTUD1 mRNA and protein was upregulated in glioma tissues and cell lines compared with normal brain tissue. Knockdown of EFTUD1 in glioma cell lines via short interfering RNA caused G1 cell cycle arrest, apoptosis, and autophagy, as well as reduced cell proliferation. The ribosome biogenesis factor EIF6, which normally was detected in the nucleus, redistributed to the perinuclear regions and cytoplasm in the absence of EFTUD1. <a href="#5" class="mim-tip-reference" title="Saito, K., Iizuka, Y., Ohta, S., Takahashi, S., Nakamura, K., Saya, H., Yoshida, K., Kawakami, Y., Toda, M. <strong>Functional analysis of a novel glioma antigen, EFTUD1.</strong> Neuro-Oncol. 16: 1618-1629, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25015090/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25015090</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25015090[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/neuonc/nou132" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25015090">Saito et al. (2014)</a> concluded that the cellular effects of EFTUD1 knockdown were due to impaired ribosome biogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25015090" 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="#2" class="mim-tip-reference" title="Garcia-Marquez, A., Gijsbers, A., de la Mora, E., Sanchez-Puig, N. <strong>Defective guanine nucleotide exchange in the elongation factor-like 1 (EFL1) GTPase by mutations in the Shwachman-Diamond syndrome protein.</strong> J. Biol. Chem. 290: 17669-17678, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25991726/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25991726</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25991726[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/10.1074/jbc.M114.626275" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25991726">Garcia-Marquez et al. (2015)</a> determined that binding of EFL1 to both GDP and GTP is a 2-step process with an initial binding event followed by a conformational change. The affinity of EFL1 for GTP was 10-fold lower than that calculated for GDP. Association of EFL1 with SBDS did not alter the affinity of EFL1 for GTP, but significantly reduced its dissociation constant for GDP. Thus, SBDS acted as a guanine nucleotide exchange factor (GEF) for EFL1, promoting activation of EFL1 by release of GDP. <a href="#2" class="mim-tip-reference" title="Garcia-Marquez, A., Gijsbers, A., de la Mora, E., Sanchez-Puig, N. <strong>Defective guanine nucleotide exchange in the elongation factor-like 1 (EFL1) GTPase by mutations in the Shwachman-Diamond syndrome protein.</strong> J. Biol. Chem. 290: 17669-17678, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25991726/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25991726</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25991726[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/10.1074/jbc.M114.626275" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25991726">Garcia-Marquez et al. (2015)</a> concluded that SBDS couples the energy liberated from the hydrolysis of GTP by EFL1 for release of EIF6 from the surface of the 60S ribosomal subunit. They further found that SBDS mutations found in patients with Shwachman-Diamond syndrome (SDS; <a href="/entry/260400">260400</a>) disrupted the interaction of SBDS with EFL1 and prevented SBDS regulation of the affinity of EFL1 toward guanine nucleotides. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25991726" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In 6 affected children from 3 unrelated families with Shwachman-Diamond syndrome (SDS2; <a href="/entry/617941">617941</a>), <a href="#6" class="mim-tip-reference" title="Stepensky, P., Chacon-Flores, M., Kim, K. H., Aburzaitoun, O., Bautista-Santos, A., Simanovsky, N., Siliqi, D., Altamura, D., Mendez-Godoy, A., Gijsbers, A., Eddin, A. N., Dor, T., Charrow, J., Sanchez-Puig, N., Elpeleg, O. <strong>Mutations in EFL1, an SBDS partner, are associated with infantile pancytopenia, exocrine pancreatic insufficiency and skeletal anomalies in a Shwachman-Diamond like syndrome.</strong> J. Med. Genet. 54: 558-566, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28331068/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28331068</a>] [<a href="https://doi.org/10.1136/jmedgenet-2016-104366" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28331068">Stepensky et al. (2017)</a> identified homozygosity for missense mutations in the EFL1 gene: 2 Mexican sibs were homozygous for an M882K substitution (<a href="#0001">617538.0001</a>), and 4 Palestinian Muslim children were homozygous for an R1095Q substitution (<a href="#0002">617538.0002</a>). Functional analysis demonstrated that the mutations impair eIF6 release from the 60s ribosomal subunit. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28331068" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Tan, Q. K.-G., Cope, H., Spillmann, R. C., Strong, N., Jiang, Y.-H., McDonald, M. T., Rothman, J. A., Butler, M. W., Frush, D. P., Lachman, R. S., Lee, B., Bacino, C. A., Bonner, M. J., McCall, C. M., Pendse, A. A., Walley, N., Undiagnosed Diseases Network, Shashi, V., Pena, L. D. M. <strong>Further evidence for the involvement of EFL1 in a Shwachman-Diamond-like syndrome and expansion of the phenotypic features.</strong> Cold Spring Harbor Molec. Case Stud. 4: a003046, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29970384/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29970384</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29970384[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/10.1101/mcs.a003046" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29970384">Tan et al. (2018)</a> identified a homozygous mutation in the EFL1 gene (<a href="#0003">617538.0003</a>) in a 14-year-old girl with SDS2. The mutation, which was identified by trio whole-exome sequencing, was present in heterozygous state in the parents. Functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29970384" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By whole-exome sequencing followed by Sanger sequencing, <a href="#8" class="mim-tip-reference" title="Tan, S., Kermasson, L., Hoslin, A., Jaako, P., Faille, A., Acevedo-Arozena, A., Lengline, E., Ranta, D., Poiree, M., Fenneteau, O., Ducou le Pointe, H., Fumagalli, S., and 9 others. <strong>EFL1 mutations impair eIF6 release to cause Shwachman-Diamond syndrome.</strong> Blood 134: 277-290, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31151987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31151987</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31151987[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1182/blood.2018893404" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31151987">Tan et al. (2019)</a> identified mutations in the EFL1 gene in 3 patients with SDS2. Compound heterozygous mutations (<a href="#0004">617538.0004</a>-<a href="#0005">617538.0005</a>) were identified in patient 1, a homozygous mutation (<a href="#0006">617538.0006</a>) was identified in patient 2, and a single heterozygous mutation (<a href="#0007">617538.0007</a>) inherited from the father was identified in patient 3. There was near absence of detectable mRNA transcripts from the maternal allele in patient 3, suggesting a noncoding mutation in the maternal allele affecting EFL1 expression. <a href="#8" class="mim-tip-reference" title="Tan, S., Kermasson, L., Hoslin, A., Jaako, P., Faille, A., Acevedo-Arozena, A., Lengline, E., Ranta, D., Poiree, M., Fenneteau, O., Ducou le Pointe, H., Fumagalli, S., and 9 others. <strong>EFL1 mutations impair eIF6 release to cause Shwachman-Diamond syndrome.</strong> Blood 134: 277-290, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31151987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31151987</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31151987[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1182/blood.2018893404" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31151987">Tan et al. (2019)</a> demonstrated that the EFL1 mutations resulted in impaired eIF6 release from the late 60S cytoplasmic subunit, causing defective ribosomal subunit joining and reduced global protein synthesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31151987" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 3 Korean patients with SDS2, <a href="#4" class="mim-tip-reference" title="Lee, S., Shin, C. H., Lee, J., Jeong, S. D., Hong, C. R., Kim, J.-D., Kim, A.-R., Pak, B., Son, S. J., Kokhan, O., Yoo, T., Ko, J. S., and 10 others. <strong>Somatic uniparental disomy mitigates the most damaging EFL1 allele combination in Shwachman-Diamond syndrome.</strong> Blood 138: 2117-2128, 2021. Note: Erratum: Blood 142: 857 only, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34115847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34115847</a>] [<a href="https://doi.org/10.1182/blood.2021010913" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34115847">Lee et al. (2021)</a> identified compound heterozygous mutations in the EIF1 gene (<a href="/entry/617535#0008">617535.0008</a>-<a href="/entry/617535#0010">617535.0010</a>); one of the mutations (T1069A; <a href="#0008">617538.0008</a>) occurred in all 3. All 3 patients also had somatic partial loss of heterozygosity (LOH) of chromosome 15, including the EIF1 gene, in bone marrow-derived cells, resulting in homozygosity for the T1069A allele in some cells. In patients I-1 and III-1, this loss of heterozygosity was not observed in non-bone marrow-derived cells. <a href="#4" class="mim-tip-reference" title="Lee, S., Shin, C. H., Lee, J., Jeong, S. D., Hong, C. R., Kim, J.-D., Kim, A.-R., Pak, B., Son, S. J., Kokhan, O., Yoo, T., Ko, J. S., and 10 others. <strong>Somatic uniparental disomy mitigates the most damaging EFL1 allele combination in Shwachman-Diamond syndrome.</strong> Blood 138: 2117-2128, 2021. Note: Erratum: Blood 142: 857 only, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34115847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34115847</a>] [<a href="https://doi.org/10.1182/blood.2021010913" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34115847">Lee et al. (2021)</a> concluded that the LOH on chromosome 15 and homozygosity for a relatively milder mutation resulted in avoidance of catastrophic consequences. EFL1 -/- HeLa cells exhibited a partial rescue of ribosome assembly when transfected with EFL1 with the T1069A mutation, suggesting that this mutation is hypomorphic. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34115847" 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="#8" class="mim-tip-reference" title="Tan, S., Kermasson, L., Hoslin, A., Jaako, P., Faille, A., Acevedo-Arozena, A., Lengline, E., Ranta, D., Poiree, M., Fenneteau, O., Ducou le Pointe, H., Fumagalli, S., and 9 others. <strong>EFL1 mutations impair eIF6 release to cause Shwachman-Diamond syndrome.</strong> Blood 134: 277-290, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31151987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31151987</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31151987[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1182/blood.2018893404" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31151987">Tan et al. (2019)</a> studied a mouse model with homozygosity for a K983R mutation in the Efl1 gene. The mice had decreased bone density, decreased weight due to a progressive loss of fat mass accumulation, and decreased bone marrow cellularity. Some of the mutant mice also had gait and memory abnormalities. Functional studies demonstrated an increased 60S:80S ribosomal subunit ratio in mouse embryonic fibroblasts from affected mice, indicating a defect in ribosomal maturation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31151987" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Lee, S., Shin, C. H., Lee, J., Jeong, S. D., Hong, C. R., Kim, J.-D., Kim, A.-R., Pak, B., Son, S. J., Kokhan, O., Yoo, T., Ko, J. S., and 10 others. <strong>Somatic uniparental disomy mitigates the most damaging EFL1 allele combination in Shwachman-Diamond syndrome.</strong> Blood 138: 2117-2128, 2021. Note: Erratum: Blood 142: 857 only, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34115847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34115847</a>] [<a href="https://doi.org/10.1182/blood.2021010913" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34115847">Lee et al. (2021)</a> generated mice that had a homozygous knockout for Efl1 and a homozygous knock-in for a T1076A mutation (orthologous to the human T1069A mutation) in the Efl1 gene. The knockout mice had embryonic lethality, whereas the knock-in T1076A mice survived to birth. After birth, knock-in mice were smaller than wildtype mice and died early. They exhibited bone marrow deficiency, including reduced hemoglobin, white blood cells, and platelets. Livers of the knock-in mice had a lower 80S ribosome peak compared to livers from wildtype mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34115847" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Lee, S., Shin, C. H., Lee, J., Jeong, S. D., Hong, C. R., Kim, J.-D., Kim, A.-R., Pak, B., Son, S. J., Kokhan, O., Yoo, T., Ko, J. S., and 10 others. <strong>Somatic uniparental disomy mitigates the most damaging EFL1 allele combination in Shwachman-Diamond syndrome.</strong> Blood 138: 2117-2128, 2021. Note: Erratum: Blood 142: 857 only, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34115847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34115847</a>] [<a href="https://doi.org/10.1182/blood.2021010913" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34115847">Lee et al. (2021)</a> studied a morpholino-targeted zebrafish model of efl1 deficiency. The morphant fish had smaller heads and eyes and impaired hematopoiesis. The phenotypes were rescued by introduction of wildtype Efl1 mRNA and partially rescued by introduction of Efl1 with the T1069A mutation (<a href="#0008">617538.0008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34115847" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a Mexican brother and sister with Shwachman-Diamond syndrome-2 (SDS2; <a href="/entry/617941">617941</a>), <a href="#6" class="mim-tip-reference" title="Stepensky, P., Chacon-Flores, M., Kim, K. H., Aburzaitoun, O., Bautista-Santos, A., Simanovsky, N., Siliqi, D., Altamura, D., Mendez-Godoy, A., Gijsbers, A., Eddin, A. N., Dor, T., Charrow, J., Sanchez-Puig, N., Elpeleg, O. <strong>Mutations in EFL1, an SBDS partner, are associated with infantile pancytopenia, exocrine pancreatic insufficiency and skeletal anomalies in a Shwachman-Diamond like syndrome.</strong> J. Med. Genet. 54: 558-566, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28331068/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28331068</a>] [<a href="https://doi.org/10.1136/jmedgenet-2016-104366" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28331068">Stepensky et al. (2017)</a> identified homozygosity for a c.2645T-A transversion (c.2645T-A, NM_024580.5) in exon 18 of the EFL1 gene, resulting in a met882-to-lys (M882K) substitution at a conserved residue. The mutation segregated with disease in the family and was not found in the ExAC database. Functional analysis in yeast cells showed that the M992K mutant cannot release eIF6 (<a href="/entry/602912">602912</a>) from the surface of the 60S ribosomal subunit. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28331068" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs376095522 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs376095522;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/rs376095522?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=rs376095522" 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=rs376095522" 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=RCV000625722 OR RCV003558479" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000625722, RCV003558479" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000625722...</a>
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<p>In 3 affected sibs and an unrelated affected girl from Palestinian Muslim families with Shwachman-Diamond syndrome-2 (SDS2; <a href="/entry/617941">617941</a>), <a href="#6" class="mim-tip-reference" title="Stepensky, P., Chacon-Flores, M., Kim, K. H., Aburzaitoun, O., Bautista-Santos, A., Simanovsky, N., Siliqi, D., Altamura, D., Mendez-Godoy, A., Gijsbers, A., Eddin, A. N., Dor, T., Charrow, J., Sanchez-Puig, N., Elpeleg, O. <strong>Mutations in EFL1, an SBDS partner, are associated with infantile pancytopenia, exocrine pancreatic insufficiency and skeletal anomalies in a Shwachman-Diamond like syndrome.</strong> J. Med. Genet. 54: 558-566, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28331068/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28331068</a>] [<a href="https://doi.org/10.1136/jmedgenet-2016-104366" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28331068">Stepensky et al. (2017)</a> identified homozygosity for a c.3284G-A transition (c.3284G-A, NM_024580.5) in the EFL1 gene, resulting in an arg1095-to-gln (R1095Q) substitution at a conserved residue. The mutation segregated with disease in the family and was not found in approximately 940 Muslim Arab in-house exomes; however, the variant was present in 2 of 60,700 exomes in the ExAC database. Functional analysis in yeast cells showed that the R1095Q mutant cannot release eIF6 (<a href="/entry/602912">602912</a>) from the surface of the 60S ribosomal subunit. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28331068" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs1441937959 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1441937959;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/rs1441937959?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=rs1441937959" 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=rs1441937959" 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=RCV000625990" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000625990" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000625990</a>
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<p>In a 14-year-old girl with Shwachman-Diamond syndrome-2 (SDS2; <a href="/entry/617941">617941</a>), <a href="#7" class="mim-tip-reference" title="Tan, Q. K.-G., Cope, H., Spillmann, R. C., Strong, N., Jiang, Y.-H., McDonald, M. T., Rothman, J. A., Butler, M. W., Frush, D. P., Lachman, R. S., Lee, B., Bacino, C. A., Bonner, M. J., McCall, C. M., Pendse, A. A., Walley, N., Undiagnosed Diseases Network, Shashi, V., Pena, L. D. M. <strong>Further evidence for the involvement of EFL1 in a Shwachman-Diamond-like syndrome and expansion of the phenotypic features.</strong> Cold Spring Harbor Molec. Case Stud. 4: a003046, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29970384/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29970384</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29970384[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/10.1101/mcs.a003046" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29970384">Tan et al. (2018)</a> identified homozygosity for a c.379A-G transition (c.379A-G, NM_024580.5) in the EFL1 gene, resulting in a thr127-to-ala (T127A) substitution at a conserved site. The mutation was identified by trio whole-exome sequencing and was present in the carrier state in the parents. The mutation was absent from an internal database of 13,119 samples and from the EVS and ExAC databases. The mutation was present in 1 of 240,260 alleles in the gnomAD database. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29970384" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs1330065864 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1330065864;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/rs1330065864?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=rs1330065864" 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=rs1330065864" 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=RCV002248311" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV002248311" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV002248311</a>
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<p>In a patient (P1) with Shwachman-Diamond syndrome-2 (SDS2; <a href="/entry/617941">617941</a>), <a href="#8" class="mim-tip-reference" title="Tan, S., Kermasson, L., Hoslin, A., Jaako, P., Faille, A., Acevedo-Arozena, A., Lengline, E., Ranta, D., Poiree, M., Fenneteau, O., Ducou le Pointe, H., Fumagalli, S., and 9 others. <strong>EFL1 mutations impair eIF6 release to cause Shwachman-Diamond syndrome.</strong> Blood 134: 277-290, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31151987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31151987</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31151987[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1182/blood.2018893404" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31151987">Tan et al. (2019)</a> identified compound heterozygous mutations in the EFL1 gene: a c.2260C-T transition, resulting in an arg754-to-ter (R754X) substitution, and a c.1514T-C transition, resulting in a phe505-to-ser (F505S; <a href="#0005">617538.0005</a>) substitution. The mutations, which were identified by whole-exome sequencing and confirmed by Sanger sequencing, were found in the carrier state in the parents and an unaffected sib. cDNA sequencing in the patient suggested reduction in the amount of transcript with the R754X mutation, indicating that the mutation resulted in partial nonsense-mediated decay. Immunoblot analysis in patient fibroblasts showed reduction of EFL1 protein expression compared to controls. <a href="#8" class="mim-tip-reference" title="Tan, S., Kermasson, L., Hoslin, A., Jaako, P., Faille, A., Acevedo-Arozena, A., Lengline, E., Ranta, D., Poiree, M., Fenneteau, O., Ducou le Pointe, H., Fumagalli, S., and 9 others. <strong>EFL1 mutations impair eIF6 release to cause Shwachman-Diamond syndrome.</strong> Blood 134: 277-290, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31151987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31151987</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31151987[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1182/blood.2018893404" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31151987">Tan et al. (2019)</a> also demonstrated that the mutations resulted in a defect in ribosomal subunit joining and a reduction in total protein synthesis in patient fibroblasts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31151987" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs763132789 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs763132789;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/rs763132789?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=rs763132789" 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=rs763132789" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>For discussion of the c.1514T-C transition in the EFL1 gene, resulting in a phe505-to-ser (F505S) substitution, that was identified in compound heterozygous state in a patient with Shwachman-Diamond syndrome-2 (SDS2; <a href="/entry/617941">617941</a>) by <a href="#8" class="mim-tip-reference" title="Tan, S., Kermasson, L., Hoslin, A., Jaako, P., Faille, A., Acevedo-Arozena, A., Lengline, E., Ranta, D., Poiree, M., Fenneteau, O., Ducou le Pointe, H., Fumagalli, S., and 9 others. <strong>EFL1 mutations impair eIF6 release to cause Shwachman-Diamond syndrome.</strong> Blood 134: 277-290, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31151987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31151987</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31151987[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1182/blood.2018893404" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31151987">Tan et al. (2019)</a>, see <a href="#0004">617538.0004</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31151987" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs757808847 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs757808847;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/rs757808847?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=rs757808847" 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=rs757808847" 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=RCV001265750 OR RCV001880096 OR RCV002251569" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001265750, RCV001880096, RCV002251569" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001265750...</a>
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<p>In a patient (P2) from Guinea, born to consanguineous parents, with Shwachman-Diamond syndrome-2 (SDS2; <a href="/entry/617941">617941</a>), <a href="#8" class="mim-tip-reference" title="Tan, S., Kermasson, L., Hoslin, A., Jaako, P., Faille, A., Acevedo-Arozena, A., Lengline, E., Ranta, D., Poiree, M., Fenneteau, O., Ducou le Pointe, H., Fumagalli, S., and 9 others. <strong>EFL1 mutations impair eIF6 release to cause Shwachman-Diamond syndrome.</strong> Blood 134: 277-290, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31151987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31151987</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31151987[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1182/blood.2018893404" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31151987">Tan et al. (2019)</a> identified a homozygous c.2908C-T transition in the EFL1 gene, resulting in an arg970-to-his (R970H) substitution. The mutation, which was identified by whole-exome sequencing and confirmed by Sanger sequencing, was found in the carrier state in the parents and 3 unaffected sibs. <a href="#8" class="mim-tip-reference" title="Tan, S., Kermasson, L., Hoslin, A., Jaako, P., Faille, A., Acevedo-Arozena, A., Lengline, E., Ranta, D., Poiree, M., Fenneteau, O., Ducou le Pointe, H., Fumagalli, S., and 9 others. <strong>EFL1 mutations impair eIF6 release to cause Shwachman-Diamond syndrome.</strong> Blood 134: 277-290, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31151987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31151987</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31151987[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1182/blood.2018893404" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31151987">Tan et al. (2019)</a> also demonstrated that the mutations resulted in an increased 60S:80S ribosomal subunit ratio and a reduction in total protein synthesis in patient fibroblasts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31151987" 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">rs2141228362 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2141228362;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=rs2141228362" 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=rs2141228362" 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=RCV002248313" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV002248313" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV002248313</a>
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<p>In a patient (P3) with Shwachman-Diamond syndrome-2 (SDS2; <a href="/entry/617941">617941</a>), <a href="#8" class="mim-tip-reference" title="Tan, S., Kermasson, L., Hoslin, A., Jaako, P., Faille, A., Acevedo-Arozena, A., Lengline, E., Ranta, D., Poiree, M., Fenneteau, O., Ducou le Pointe, H., Fumagalli, S., and 9 others. <strong>EFL1 mutations impair eIF6 release to cause Shwachman-Diamond syndrome.</strong> Blood 134: 277-290, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31151987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31151987</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31151987[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1182/blood.2018893404" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31151987">Tan et al. (2019)</a> identified heterozygosity for a c.2647T-G transversion in the EFL1 gene, resulting in a cys883-to-gly (C883G) substitution. The mutation, which was identified by whole-exome sequencing and confirmed by Sanger sequencing, was found in the carrier state in the father and an unaffected sib. A second mutation was not identified; however, there was near absence of detectable mRNA transcripts from the maternal allele, suggesting a noncoding mutation in the maternal allele affecting EFL1 expression. Immunoblot analysis in patient lymphoblastoid cell lines demonstrated reduced EFL1 protein expression. <a href="#8" class="mim-tip-reference" title="Tan, S., Kermasson, L., Hoslin, A., Jaako, P., Faille, A., Acevedo-Arozena, A., Lengline, E., Ranta, D., Poiree, M., Fenneteau, O., Ducou le Pointe, H., Fumagalli, S., and 9 others. <strong>EFL1 mutations impair eIF6 release to cause Shwachman-Diamond syndrome.</strong> Blood 134: 277-290, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31151987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31151987</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31151987[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1182/blood.2018893404" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31151987">Tan et al. (2019)</a> also demonstrated that the mutation resulted in a defect in ribosomal subunit joining and a reduction in total protein synthesis in patient fibroblasts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31151987" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs756494164 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs756494164;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/rs756494164?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=rs756494164" 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=rs756494164" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a Korean patient (patient I-1) with Shwachman-Diamond syndrome-2 (SDS2; <a href="/entry/617941">617941</a>), <a href="#4" class="mim-tip-reference" title="Lee, S., Shin, C. H., Lee, J., Jeong, S. D., Hong, C. R., Kim, J.-D., Kim, A.-R., Pak, B., Son, S. J., Kokhan, O., Yoo, T., Ko, J. S., and 10 others. <strong>Somatic uniparental disomy mitigates the most damaging EFL1 allele combination in Shwachman-Diamond syndrome.</strong> Blood 138: 2117-2128, 2021. Note: Erratum: Blood 142: 857 only, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34115847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34115847</a>] [<a href="https://doi.org/10.1182/blood.2021010913" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34115847">Lee et al. (2021)</a> identified compound heterozygous mutations in the EFL1 gene: a c.3205A-G transition (c.3205A-G, NM_024580.5), resulting in a thr1069-to-ala (T1069A) substitution, and a 1-bp duplication (c.2478dupT; <a href="#0009">617538.0009</a>), resulting in a frameshift and premature termination (Gly827TrpfsTer13). The mutations were identified by whole-exome sequencing and the parents were shown to be mutation carriers. The T1069A mutation was present in the gnomAD database at a frequency of 3/17972 and the c.2478dupT mutation was not present in the gnomAD database. In the patient, the c.2478dupT mutation was present at an allele frequency of 8.3% based on the whole-exome sequencing in blood and a frequency of 15% based on amplicon sequencing in blood and bone marrow but a frequency of 50% in most other tissues. <a href="#4" class="mim-tip-reference" title="Lee, S., Shin, C. H., Lee, J., Jeong, S. D., Hong, C. R., Kim, J.-D., Kim, A.-R., Pak, B., Son, S. J., Kokhan, O., Yoo, T., Ko, J. S., and 10 others. <strong>Somatic uniparental disomy mitigates the most damaging EFL1 allele combination in Shwachman-Diamond syndrome.</strong> Blood 138: 2117-2128, 2021. Note: Erratum: Blood 142: 857 only, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34115847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34115847</a>] [<a href="https://doi.org/10.1182/blood.2021010913" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34115847">Lee et al. (2021)</a> determined that there was a copy neutral, somatic partial loss of heterozygosity including the EFL1 locus, resulting in homozygosity for the maternally inherited T1069A mutation, that was restricted to the bone marrow. EFL1-/- HeLa cells exhibited a partial rescue of ribosome assembly when transfected with EFL1 with the T1069A mutation, suggesting that this mutation is hypomorphic. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34115847" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 unrelated Korean patients (patients II-1 and III-1) with SDS2, <a href="#4" class="mim-tip-reference" title="Lee, S., Shin, C. H., Lee, J., Jeong, S. D., Hong, C. R., Kim, J.-D., Kim, A.-R., Pak, B., Son, S. J., Kokhan, O., Yoo, T., Ko, J. S., and 10 others. <strong>Somatic uniparental disomy mitigates the most damaging EFL1 allele combination in Shwachman-Diamond syndrome.</strong> Blood 138: 2117-2128, 2021. Note: Erratum: Blood 142: 857 only, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34115847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34115847</a>] [<a href="https://doi.org/10.1182/blood.2021010913" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34115847">Lee et al. (2021)</a> identified compound heterozygous mutations in the EFL1 gene: T1069A and a c.89A-G transition, resulting in a his30-to-arg (H30R; <a href="#0010">617538.0010</a>) substitution. The mutations were identified by whole-exome sequencing. The H30R mutation was present in the gnomAD database at a frequency of 5.1 x 10(-5). In patients II-1 and III-1, the H30R mutation was present at an allele frequency of 14.8% and 36.8%, respectively, based on the whole-exome sequencing in blood. Both patients had a copy neutral, somatic partial loss of heterozygosity including the EFL1 locus, resulting in partial homozygosity for the T1069A mutation. Amplicon sequencing in buccal cells from patient III-1 demonstrated an allele frequency of 52.5% for the T1069A mutation and 47.3% for the H30R mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34115847" 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">rs1380341628 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1380341628;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=rs1380341628" 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=rs1380341628" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>For discussion of the 1-bp duplication (c.2478dupT, NM_024580.5) in the EFL1 gene, resulting in a frameshift and premature termination (Gly827fsTer13), that was identified in compound heterozygous state in a patient with Shwachman-Diamond syndrome-2 (SDS2; <a href="/entry/617941">617941</a>) by <a href="#4" class="mim-tip-reference" title="Lee, S., Shin, C. H., Lee, J., Jeong, S. D., Hong, C. R., Kim, J.-D., Kim, A.-R., Pak, B., Son, S. J., Kokhan, O., Yoo, T., Ko, J. S., and 10 others. <strong>Somatic uniparental disomy mitigates the most damaging EFL1 allele combination in Shwachman-Diamond syndrome.</strong> Blood 138: 2117-2128, 2021. Note: Erratum: Blood 142: 857 only, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34115847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34115847</a>] [<a href="https://doi.org/10.1182/blood.2021010913" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34115847">Lee et al. (2021)</a>, see <a href="#0008">617538.0008</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34115847" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs370108445 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs370108445;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/rs370108445?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=rs370108445" 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=rs370108445" 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=RCV002248316" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV002248316" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV002248316</a>
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<p>For discussion of the c.89A-G transition (c.89A-G, NM_024580.5) in the EFL1 gene, resulting in a his30-to-arg (H30R) substitution, that was identified in compound heterozygous state in 2 patients with Shwachman-Diamond syndrome-2 (SDS2; <a href="/entry/617941">617941</a>) by <a href="#4" class="mim-tip-reference" title="Lee, S., Shin, C. H., Lee, J., Jeong, S. D., Hong, C. R., Kim, J.-D., Kim, A.-R., Pak, B., Son, S. J., Kokhan, O., Yoo, T., Ko, J. S., and 10 others. <strong>Somatic uniparental disomy mitigates the most damaging EFL1 allele combination in Shwachman-Diamond syndrome.</strong> Blood 138: 2117-2128, 2021. Note: Erratum: Blood 142: 857 only, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34115847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34115847</a>] [<a href="https://doi.org/10.1182/blood.2021010913" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34115847">Lee et al. (2021)</a>, see <a href="#0008">617538.0008</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34115847" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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<a id="Finch2011" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Finch, A. J., Hilcenko, C., Basse, N., Drynan, L. F., Goyenechea, B., Menne, T. F., Gonzalez Fernandez, A., Simpson, P., D'Santos, C. S., Arends, M. J., Donadieu, J., Bellanne-Chantelot, C., Costanzo, M., Boone, C., McKenzie, A. N., Freund, S. M. V., Warren, A. J.
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<strong>Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes Shwachman-Diamond syndrome.</strong>
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Genes Dev. 25: 917-929, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21536732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21536732</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21536732[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=21536732" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1101/gad.623011" target="_blank">Full Text</a>]
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<a id="Garcia-Marquez2015" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Garcia-Marquez, A., Gijsbers, A., de la Mora, E., Sanchez-Puig, N.
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<strong>Defective guanine nucleotide exchange in the elongation factor-like 1 (EFL1) GTPase by mutations in the Shwachman-Diamond syndrome protein.</strong>
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J. Biol. Chem. 290: 17669-17678, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25991726/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25991726</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25991726[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=25991726" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.M114.626275" target="_blank">Full Text</a>]
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<a id="Hartz2017" class="mim-anchor"></a>
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<p class="mim-text-font">
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Hartz, P. A.
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<strong>Personal Communication.</strong>
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Baltimore, Md. June 6, 2017.
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<a id="Lee2021" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Lee, S., Shin, C. H., Lee, J., Jeong, S. D., Hong, C. R., Kim, J.-D., Kim, A.-R., Pak, B., Son, S. J., Kokhan, O., Yoo, T., Ko, J. S., and 10 others.
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<strong>Somatic uniparental disomy mitigates the most damaging EFL1 allele combination in Shwachman-Diamond syndrome.</strong>
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Blood 138: 2117-2128, 2021. Note: Erratum: Blood 142: 857 only, 2023.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34115847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34115847</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34115847" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1182/blood.2021010913" target="_blank">Full Text</a>]
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<a id="5" class="mim-anchor"></a>
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<a id="Saito2014" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Saito, K., Iizuka, Y., Ohta, S., Takahashi, S., Nakamura, K., Saya, H., Yoshida, K., Kawakami, Y., Toda, M.
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<strong>Functional analysis of a novel glioma antigen, EFTUD1.</strong>
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Neuro-Oncol. 16: 1618-1629, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25015090/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25015090</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25015090[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=25015090" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/neuonc/nou132" target="_blank">Full Text</a>]
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<a id="Stepensky2017" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Stepensky, P., Chacon-Flores, M., Kim, K. H., Aburzaitoun, O., Bautista-Santos, A., Simanovsky, N., Siliqi, D., Altamura, D., Mendez-Godoy, A., Gijsbers, A., Eddin, A. N., Dor, T., Charrow, J., Sanchez-Puig, N., Elpeleg, O.
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<strong>Mutations in EFL1, an SBDS partner, are associated with infantile pancytopenia, exocrine pancreatic insufficiency and skeletal anomalies in a Shwachman-Diamond like syndrome.</strong>
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J. Med. Genet. 54: 558-566, 2017.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28331068/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28331068</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28331068" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1136/jmedgenet-2016-104366" target="_blank">Full Text</a>]
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<a id="7" class="mim-anchor"></a>
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<a id="Tan2018" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tan, Q. K.-G., Cope, H., Spillmann, R. C., Strong, N., Jiang, Y.-H., McDonald, M. T., Rothman, J. A., Butler, M. W., Frush, D. P., Lachman, R. S., Lee, B., Bacino, C. A., Bonner, M. J., McCall, C. M., Pendse, A. A., Walley, N., Undiagnosed Diseases Network, Shashi, V., Pena, L. D. M.
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<strong>Further evidence for the involvement of EFL1 in a Shwachman-Diamond-like syndrome and expansion of the phenotypic features.</strong>
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Cold Spring Harbor Molec. Case Stud. 4: a003046, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29970384/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29970384</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29970384[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=29970384" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1101/mcs.a003046" target="_blank">Full Text</a>]
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<a id="Tan2019" class="mim-anchor"></a>
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Tan, S., Kermasson, L., Hoslin, A., Jaako, P., Faille, A., Acevedo-Arozena, A., Lengline, E., Ranta, D., Poiree, M., Fenneteau, O., Ducou le Pointe, H., Fumagalli, S., and 9 others.
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<strong>EFL1 mutations impair eIF6 release to cause Shwachman-Diamond syndrome.</strong>
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Blood 134: 277-290, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31151987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31151987</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31151987[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=31151987" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1182/blood.2018893404" target="_blank">Full Text</a>]
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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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Hilary J. Vernon - updated : 04/15/2022
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<div class="row collapse" id="mimCollapseContributors">
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 04/19/2018
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<span class="mim-text-font">
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Patricia A. Hartz : 06/19/2017
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<span class="mim-text-font">
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alopez : 01/29/2024
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<span class="mim-text-font">
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carol : 04/18/2022<br>carol : 04/15/2022<br>carol : 04/19/2018<br>carol : 06/19/2017
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<strong>*</strong> 617538
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<span class="mim-font">
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ELONGATION FACTOR-LIKE GTPase 1; EFL1
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<em>Alternative titles; symbols</em>
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<span class="mim-font">
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RIBOSOME ASSEMBLY 1 HOMOLOG; RIA1<br />
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ELONGATION FACTOR Tu GTP-BINDING DOMAIN-CONTAINING 1; EFTUD1<br />
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FAM42A
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: EFL1</em></strong>
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<strong>
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<em>
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Cytogenetic location: 15q25.2
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Genomic coordinates <span class="small">(GRCh38)</span> : 15:82,130,233-82,262,734 </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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<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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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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Location
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</th>
|
|
<th>
|
|
Phenotype
|
|
</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">
|
|
15q25.2
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Shwachman-Diamond syndrome 2
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
617941
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>EFL1 is a GTPase that acts in concert with SBDS (607444) in the cytoplasmic maturation of the 60S ribosomal subunit by catalyzing GTP-dependent removal of the assembly factor EIF6 (602912) from the maturing ribosome (Finch et al., 2011). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By searching for the human ortholog of yeast Efl1, Finch et al. (2011) identified EFL1. The deduced 1,120-amino acid protein has 5 conserved GTPase motifs, including the GTP-binding G domain. By Western blot analysis of glioma tissues and cell lines, Saito et al. (2014) found that EFTUD1 had an apparent molecular mass of 125 kD. Immunohistochemical analysis revealed predominant EFTUD1 expression in the cytoplasm, with little expression in the nucleus. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Hartz (2017) mapped the EFL1 gene to chromosome 15q25.2 based on an alignment of the EFL1 sequence (GenBank AK023181) with the genomic sequence (GRCh38).</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Finch et al. (2011) showed that GTP and recombinant human SBDS and EFL1 cooperated to trigger release of human EIF6 (602912) from pre60S ribosomes isolated from Sbds-deficient mouse livers. EFL1 and SBDS independently and noncooperatively bound to the 60S subunit in vitro. The 60S subunit activated the GTPase activity of EFL1, but SBDS was required to stimulate EIF6 release. Two SBDS mutants with different SDS-associated missense mutations varied in their ability to enhance 60S-dependent GTPase activity of EFL1, but neither triggered EIF6 release. Finch et al. (2011) concluded that SBDS and EFL1 catalyze translational activation and proposed that SDS is a ribosomopathy caused by uncoupling GTP hydrolysis from EIF6 release. </p><p>Using quantitative PCR and Western blot analysis, Saito et al. (2014) found that expression of EFTUD1 mRNA and protein was upregulated in glioma tissues and cell lines compared with normal brain tissue. Knockdown of EFTUD1 in glioma cell lines via short interfering RNA caused G1 cell cycle arrest, apoptosis, and autophagy, as well as reduced cell proliferation. The ribosome biogenesis factor EIF6, which normally was detected in the nucleus, redistributed to the perinuclear regions and cytoplasm in the absence of EFTUD1. Saito et al. (2014) concluded that the cellular effects of EFTUD1 knockdown were due to impaired ribosome biogenesis. </p><p>Garcia-Marquez et al. (2015) determined that binding of EFL1 to both GDP and GTP is a 2-step process with an initial binding event followed by a conformational change. The affinity of EFL1 for GTP was 10-fold lower than that calculated for GDP. Association of EFL1 with SBDS did not alter the affinity of EFL1 for GTP, but significantly reduced its dissociation constant for GDP. Thus, SBDS acted as a guanine nucleotide exchange factor (GEF) for EFL1, promoting activation of EFL1 by release of GDP. Garcia-Marquez et al. (2015) concluded that SBDS couples the energy liberated from the hydrolysis of GTP by EFL1 for release of EIF6 from the surface of the 60S ribosomal subunit. They further found that SBDS mutations found in patients with Shwachman-Diamond syndrome (SDS; 260400) disrupted the interaction of SBDS with EFL1 and prevented SBDS regulation of the affinity of EFL1 toward guanine nucleotides. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In 6 affected children from 3 unrelated families with Shwachman-Diamond syndrome (SDS2; 617941), Stepensky et al. (2017) identified homozygosity for missense mutations in the EFL1 gene: 2 Mexican sibs were homozygous for an M882K substitution (617538.0001), and 4 Palestinian Muslim children were homozygous for an R1095Q substitution (617538.0002). Functional analysis demonstrated that the mutations impair eIF6 release from the 60s ribosomal subunit. </p><p>Tan et al. (2018) identified a homozygous mutation in the EFL1 gene (617538.0003) in a 14-year-old girl with SDS2. The mutation, which was identified by trio whole-exome sequencing, was present in heterozygous state in the parents. Functional studies were not performed. </p><p>By whole-exome sequencing followed by Sanger sequencing, Tan et al. (2019) identified mutations in the EFL1 gene in 3 patients with SDS2. Compound heterozygous mutations (617538.0004-617538.0005) were identified in patient 1, a homozygous mutation (617538.0006) was identified in patient 2, and a single heterozygous mutation (617538.0007) inherited from the father was identified in patient 3. There was near absence of detectable mRNA transcripts from the maternal allele in patient 3, suggesting a noncoding mutation in the maternal allele affecting EFL1 expression. Tan et al. (2019) demonstrated that the EFL1 mutations resulted in impaired eIF6 release from the late 60S cytoplasmic subunit, causing defective ribosomal subunit joining and reduced global protein synthesis. </p><p>In 3 Korean patients with SDS2, Lee et al. (2021) identified compound heterozygous mutations in the EIF1 gene (617535.0008-617535.0010); one of the mutations (T1069A; 617538.0008) occurred in all 3. All 3 patients also had somatic partial loss of heterozygosity (LOH) of chromosome 15, including the EIF1 gene, in bone marrow-derived cells, resulting in homozygosity for the T1069A allele in some cells. In patients I-1 and III-1, this loss of heterozygosity was not observed in non-bone marrow-derived cells. Lee et al. (2021) concluded that the LOH on chromosome 15 and homozygosity for a relatively milder mutation resulted in avoidance of catastrophic consequences. EFL1 -/- HeLa cells exhibited a partial rescue of ribosome assembly when transfected with EFL1 with the T1069A mutation, suggesting that this mutation is hypomorphic. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Tan et al. (2019) studied a mouse model with homozygosity for a K983R mutation in the Efl1 gene. The mice had decreased bone density, decreased weight due to a progressive loss of fat mass accumulation, and decreased bone marrow cellularity. Some of the mutant mice also had gait and memory abnormalities. Functional studies demonstrated an increased 60S:80S ribosomal subunit ratio in mouse embryonic fibroblasts from affected mice, indicating a defect in ribosomal maturation. </p><p>Lee et al. (2021) generated mice that had a homozygous knockout for Efl1 and a homozygous knock-in for a T1076A mutation (orthologous to the human T1069A mutation) in the Efl1 gene. The knockout mice had embryonic lethality, whereas the knock-in T1076A mice survived to birth. After birth, knock-in mice were smaller than wildtype mice and died early. They exhibited bone marrow deficiency, including reduced hemoglobin, white blood cells, and platelets. Livers of the knock-in mice had a lower 80S ribosome peak compared to livers from wildtype mice. </p><p>Lee et al. (2021) studied a morpholino-targeted zebrafish model of efl1 deficiency. The morphant fish had smaller heads and eyes and impaired hematopoiesis. The phenotypes were rescued by introduction of wildtype Efl1 mRNA and partially rescued by introduction of Efl1 with the T1069A mutation (617538.0008). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>10 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 SHWACHMAN-DIAMOND SYNDROME 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
EFL1, MET882LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1316615934,
|
|
|
|
|
|
gnomAD: rs1316615934,
|
|
|
|
|
|
ClinVar: RCV000625721
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Mexican brother and sister with Shwachman-Diamond syndrome-2 (SDS2; 617941), Stepensky et al. (2017) identified homozygosity for a c.2645T-A transversion (c.2645T-A, NM_024580.5) in exon 18 of the EFL1 gene, resulting in a met882-to-lys (M882K) substitution at a conserved residue. The mutation segregated with disease in the family and was not found in the ExAC database. Functional analysis in yeast cells showed that the M992K mutant cannot release eIF6 (602912) from the surface of the 60S ribosomal subunit. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 SHWACHMAN-DIAMOND SYNDROME 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
EFL1, ARG1095GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs376095522,
|
|
|
|
|
|
gnomAD: rs376095522,
|
|
|
|
|
|
ClinVar: RCV000625722, RCV003558479
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 affected sibs and an unrelated affected girl from Palestinian Muslim families with Shwachman-Diamond syndrome-2 (SDS2; 617941), Stepensky et al. (2017) identified homozygosity for a c.3284G-A transition (c.3284G-A, NM_024580.5) in the EFL1 gene, resulting in an arg1095-to-gln (R1095Q) substitution at a conserved residue. The mutation segregated with disease in the family and was not found in approximately 940 Muslim Arab in-house exomes; however, the variant was present in 2 of 60,700 exomes in the ExAC database. Functional analysis in yeast cells showed that the R1095Q mutant cannot release eIF6 (602912) from the surface of the 60S ribosomal subunit. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 SHWACHMAN-DIAMOND SYNDROME 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
EFL1, THR127ALA
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1441937959,
|
|
|
|
|
|
gnomAD: rs1441937959,
|
|
|
|
|
|
ClinVar: RCV000625990
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 14-year-old girl with Shwachman-Diamond syndrome-2 (SDS2; 617941), Tan et al. (2018) identified homozygosity for a c.379A-G transition (c.379A-G, NM_024580.5) in the EFL1 gene, resulting in a thr127-to-ala (T127A) substitution at a conserved site. The mutation was identified by trio whole-exome sequencing and was present in the carrier state in the parents. The mutation was absent from an internal database of 13,119 samples and from the EVS and ExAC databases. The mutation was present in 1 of 240,260 alleles in the gnomAD database. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 SHWACHMAN-DIAMOND SYNDROME 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
EFL1, ARG754TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1330065864,
|
|
|
|
|
|
gnomAD: rs1330065864,
|
|
|
|
|
|
ClinVar: RCV002248311
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient (P1) with Shwachman-Diamond syndrome-2 (SDS2; 617941), Tan et al. (2019) identified compound heterozygous mutations in the EFL1 gene: a c.2260C-T transition, resulting in an arg754-to-ter (R754X) substitution, and a c.1514T-C transition, resulting in a phe505-to-ser (F505S; 617538.0005) substitution. The mutations, which were identified by whole-exome sequencing and confirmed by Sanger sequencing, were found in the carrier state in the parents and an unaffected sib. cDNA sequencing in the patient suggested reduction in the amount of transcript with the R754X mutation, indicating that the mutation resulted in partial nonsense-mediated decay. Immunoblot analysis in patient fibroblasts showed reduction of EFL1 protein expression compared to controls. Tan et al. (2019) also demonstrated that the mutations resulted in a defect in ribosomal subunit joining and a reduction in total protein synthesis in patient fibroblasts. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 SHWACHMAN-DIAMOND SYNDROME 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
EFL1, PHE505SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs763132789,
|
|
|
|
|
|
gnomAD: rs763132789,
|
|
|
|
|
|
ClinVar: RCV002248312
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the c.1514T-C transition in the EFL1 gene, resulting in a phe505-to-ser (F505S) substitution, that was identified in compound heterozygous state in a patient with Shwachman-Diamond syndrome-2 (SDS2; 617941) by Tan et al. (2019), see 617538.0004. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 SHWACHMAN-DIAMOND SYNDROME 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
EFL1, ARG970HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs757808847,
|
|
|
|
|
|
gnomAD: rs757808847,
|
|
|
|
|
|
ClinVar: RCV001265750, RCV001880096, RCV002251569
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient (P2) from Guinea, born to consanguineous parents, with Shwachman-Diamond syndrome-2 (SDS2; 617941), Tan et al. (2019) identified a homozygous c.2908C-T transition in the EFL1 gene, resulting in an arg970-to-his (R970H) substitution. The mutation, which was identified by whole-exome sequencing and confirmed by Sanger sequencing, was found in the carrier state in the parents and 3 unaffected sibs. Tan et al. (2019) also demonstrated that the mutations resulted in an increased 60S:80S ribosomal subunit ratio and a reduction in total protein synthesis in patient fibroblasts. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 SHWACHMAN-DIAMOND SYNDROME 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
EFL1, CYS883GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2141228362,
|
|
|
|
|
|
|
|
ClinVar: RCV002248313
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
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<p>In a patient (P3) with Shwachman-Diamond syndrome-2 (SDS2; 617941), Tan et al. (2019) identified heterozygosity for a c.2647T-G transversion in the EFL1 gene, resulting in a cys883-to-gly (C883G) substitution. The mutation, which was identified by whole-exome sequencing and confirmed by Sanger sequencing, was found in the carrier state in the father and an unaffected sib. A second mutation was not identified; however, there was near absence of detectable mRNA transcripts from the maternal allele, suggesting a noncoding mutation in the maternal allele affecting EFL1 expression. Immunoblot analysis in patient lymphoblastoid cell lines demonstrated reduced EFL1 protein expression. Tan et al. (2019) also demonstrated that the mutation resulted in a defect in ribosomal subunit joining and a reduction in total protein synthesis in patient fibroblasts. </p>
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<span class="mim-font">
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<strong>.0008 SHWACHMAN-DIAMOND SYNDROME 2</strong>
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</h4>
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EFL1, THR1069ALA
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<br />
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SNP: rs756494164,
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gnomAD: rs756494164,
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ClinVar: RCV002248314
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<p>In a Korean patient (patient I-1) with Shwachman-Diamond syndrome-2 (SDS2; 617941), Lee et al. (2021) identified compound heterozygous mutations in the EFL1 gene: a c.3205A-G transition (c.3205A-G, NM_024580.5), resulting in a thr1069-to-ala (T1069A) substitution, and a 1-bp duplication (c.2478dupT; 617538.0009), resulting in a frameshift and premature termination (Gly827TrpfsTer13). The mutations were identified by whole-exome sequencing and the parents were shown to be mutation carriers. The T1069A mutation was present in the gnomAD database at a frequency of 3/17972 and the c.2478dupT mutation was not present in the gnomAD database. In the patient, the c.2478dupT mutation was present at an allele frequency of 8.3% based on the whole-exome sequencing in blood and a frequency of 15% based on amplicon sequencing in blood and bone marrow but a frequency of 50% in most other tissues. Lee et al. (2021) determined that there was a copy neutral, somatic partial loss of heterozygosity including the EFL1 locus, resulting in homozygosity for the maternally inherited T1069A mutation, that was restricted to the bone marrow. EFL1-/- HeLa cells exhibited a partial rescue of ribosome assembly when transfected with EFL1 with the T1069A mutation, suggesting that this mutation is hypomorphic. </p><p>In 2 unrelated Korean patients (patients II-1 and III-1) with SDS2, Lee et al. (2021) identified compound heterozygous mutations in the EFL1 gene: T1069A and a c.89A-G transition, resulting in a his30-to-arg (H30R; 617538.0010) substitution. The mutations were identified by whole-exome sequencing. The H30R mutation was present in the gnomAD database at a frequency of 5.1 x 10(-5). In patients II-1 and III-1, the H30R mutation was present at an allele frequency of 14.8% and 36.8%, respectively, based on the whole-exome sequencing in blood. Both patients had a copy neutral, somatic partial loss of heterozygosity including the EFL1 locus, resulting in partial homozygosity for the T1069A mutation. Amplicon sequencing in buccal cells from patient III-1 demonstrated an allele frequency of 52.5% for the T1069A mutation and 47.3% for the H30R mutation. </p>
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<h4>
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<span class="mim-font">
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<strong>.0009 SHWACHMAN-DIAMOND SYNDROME 2</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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EFL1, 1-BP DUP, 2478T
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SNP: rs1380341628,
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ClinVar: RCV002248315
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<span class="mim-text-font">
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<p>For discussion of the 1-bp duplication (c.2478dupT, NM_024580.5) in the EFL1 gene, resulting in a frameshift and premature termination (Gly827fsTer13), that was identified in compound heterozygous state in a patient with Shwachman-Diamond syndrome-2 (SDS2; 617941) by Lee et al. (2021), see 617538.0008. </p>
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</span>
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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>.0010 SHWACHMAN-DIAMOND SYNDROME 2</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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EFL1, HIS30ARG
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<br />
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SNP: rs370108445,
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gnomAD: rs370108445,
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ClinVar: RCV002248316
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</span>
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<span class="mim-text-font">
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<p>For discussion of the c.89A-G transition (c.89A-G, NM_024580.5) in the EFL1 gene, resulting in a his30-to-arg (H30R) substitution, that was identified in compound heterozygous state in 2 patients with Shwachman-Diamond syndrome-2 (SDS2; 617941) by Lee et al. (2021), see 617538.0008. </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>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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<ol>
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<li>
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Finch, A. J., Hilcenko, C., Basse, N., Drynan, L. F., Goyenechea, B., Menne, T. F., Gonzalez Fernandez, A., Simpson, P., D'Santos, C. S., Arends, M. J., Donadieu, J., Bellanne-Chantelot, C., Costanzo, M., Boone, C., McKenzie, A. N., Freund, S. M. V., Warren, A. J.
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<strong>Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes Shwachman-Diamond syndrome.</strong>
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Genes Dev. 25: 917-929, 2011.
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[PubMed: 21536732]
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[Full Text: https://doi.org/10.1101/gad.623011]
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</li>
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<li>
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<p class="mim-text-font">
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Garcia-Marquez, A., Gijsbers, A., de la Mora, E., Sanchez-Puig, N.
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<strong>Defective guanine nucleotide exchange in the elongation factor-like 1 (EFL1) GTPase by mutations in the Shwachman-Diamond syndrome protein.</strong>
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J. Biol. Chem. 290: 17669-17678, 2015.
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[PubMed: 25991726]
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[Full Text: https://doi.org/10.1074/jbc.M114.626275]
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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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Hartz, P. A.
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<strong>Personal Communication.</strong>
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Baltimore, Md. June 6, 2017.
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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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Lee, S., Shin, C. H., Lee, J., Jeong, S. D., Hong, C. R., Kim, J.-D., Kim, A.-R., Pak, B., Son, S. J., Kokhan, O., Yoo, T., Ko, J. S., and 10 others.
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<strong>Somatic uniparental disomy mitigates the most damaging EFL1 allele combination in Shwachman-Diamond syndrome.</strong>
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Blood 138: 2117-2128, 2021. Note: Erratum: Blood 142: 857 only, 2023.
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[PubMed: 34115847]
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[Full Text: https://doi.org/10.1182/blood.2021010913]
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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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Saito, K., Iizuka, Y., Ohta, S., Takahashi, S., Nakamura, K., Saya, H., Yoshida, K., Kawakami, Y., Toda, M.
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<strong>Functional analysis of a novel glioma antigen, EFTUD1.</strong>
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Neuro-Oncol. 16: 1618-1629, 2014.
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[PubMed: 25015090]
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[Full Text: https://doi.org/10.1093/neuonc/nou132]
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<li>
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Stepensky, P., Chacon-Flores, M., Kim, K. H., Aburzaitoun, O., Bautista-Santos, A., Simanovsky, N., Siliqi, D., Altamura, D., Mendez-Godoy, A., Gijsbers, A., Eddin, A. N., Dor, T., Charrow, J., Sanchez-Puig, N., Elpeleg, O.
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<strong>Mutations in EFL1, an SBDS partner, are associated with infantile pancytopenia, exocrine pancreatic insufficiency and skeletal anomalies in a Shwachman-Diamond like syndrome.</strong>
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J. Med. Genet. 54: 558-566, 2017.
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[PubMed: 28331068]
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[Full Text: https://doi.org/10.1136/jmedgenet-2016-104366]
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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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Tan, Q. K.-G., Cope, H., Spillmann, R. C., Strong, N., Jiang, Y.-H., McDonald, M. T., Rothman, J. A., Butler, M. W., Frush, D. P., Lachman, R. S., Lee, B., Bacino, C. A., Bonner, M. J., McCall, C. M., Pendse, A. A., Walley, N., Undiagnosed Diseases Network, Shashi, V., Pena, L. D. M.
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<strong>Further evidence for the involvement of EFL1 in a Shwachman-Diamond-like syndrome and expansion of the phenotypic features.</strong>
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Cold Spring Harbor Molec. Case Stud. 4: a003046, 2018.
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[PubMed: 29970384]
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[Full Text: https://doi.org/10.1101/mcs.a003046]
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<li>
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<p class="mim-text-font">
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Tan, S., Kermasson, L., Hoslin, A., Jaako, P., Faille, A., Acevedo-Arozena, A., Lengline, E., Ranta, D., Poiree, M., Fenneteau, O., Ducou le Pointe, H., Fumagalli, S., and 9 others.
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<strong>EFL1 mutations impair eIF6 release to cause Shwachman-Diamond syndrome.</strong>
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Blood 134: 277-290, 2019.
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[PubMed: 31151987]
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[Full Text: https://doi.org/10.1182/blood.2018893404]
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Hilary J. Vernon - updated : 04/15/2022<br>Marla J. F. O'Neill - updated : 04/19/2018
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