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Entry
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- *608005 - SIL1 NUCLEOTIDE EXCHANGE FACTOR; SIL1
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- OMIM
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</form>
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*608005</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/608005">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=ENSG00000120725;t=ENST00000394817" 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=64374" 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=608005" 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=ENSG00000120725;t=ENST00000394817" 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_001037633,NM_022464,XM_011543570,XM_047417496,XM_047417498" 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_022464" 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=608005" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
|
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</div>
|
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</div>
|
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
|
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<span class="panel-title">
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<span class="small">
|
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
|
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</a>
|
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=12150&isoform_id=12150_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
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<div><a href="https://www.proteinatlas.org/search/SIL1" 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/11558402,11968009,15079466,22760180,22761097,26225130,37183018,45503188,68303306,74733533,77020838,77020840,83641896,119582524,119582525,767936329,957951448,957951451,2217356700,2217356702,2462603574,2462603576,2462603578" 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/Q9H173" 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=64374" 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=ENSG00000120725;t=ENST00000394817" 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=SIL1" 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=SIL1" 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+64374" 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/SIL1" 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:64374" 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/64374" 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=chr5&hgg_gene=ENST00000394817.7&hgg_start=138946724&hgg_end=139198368&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:24624" 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://search.clinicalgenome.org/kb/genes/HGNC:24624" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/sil1" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=608005[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=608005[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/ENSG00000120725" 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=SIL1" 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=SIL1" 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=SIL1" 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=SIL1&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/PA142670916" 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:24624" 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/FBgn0039296.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:1932040" 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/SIL1#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:1932040" 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/64374/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=64374" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-160113-49" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:64374" 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=SIL1&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 80734006<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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608005
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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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SIL1 NUCLEOTIDE EXCHANGE FACTOR; SIL1
|
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
SIL1, S. CEREVISIAE, HOMOLOG OF<br />
|
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BIP-ASSOCIATED PROTEIN; BAP
|
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
|
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=SIL1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">SIL1</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
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Cytogenetic location: <a href="/geneMap/5/515?start=-3&limit=10&highlight=515">5q31.2</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr5:138946724-139198368&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'})">5:138,946,724-139,198,368</a> </span>
|
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</em>
|
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</strong>
|
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
|
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<br />
|
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
|
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</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
|
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<tr class="active">
|
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<th>
|
|
Location
|
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
|
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</th>
|
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<th>
|
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Phenotype <br /> mapping key
|
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</th>
|
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</tr>
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</thead>
|
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<tbody>
|
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|
<tr>
|
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<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/5/515?start=-3&limit=10&highlight=515">
|
|
5q31.2
|
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</a>
|
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</span>
|
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</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Marinesco-Sjogren syndrome
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/248800"> 248800 </a>
|
|
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
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</td>
|
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/608005" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/608005" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
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<p>SIL1 is a resident endoplasmic reticulum (ER) glycoprotein that interacts with the ATPase domain of BIP (HSPA5; <a href="/entry/138120">138120</a>) and enhances nucleotide exchange.</p>
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<p>By searching EST databases for sequences showing similarity to yeast Sil1, <a href="#12" class="mim-tip-reference" title="Tyson, J. R., Stirling, C. J. <strong>LHS1 and SIL1 provide a lumenal function that is essential for protein translocation into the endoplasmic reticulum.</strong> EMBO J. 19: 6440-6452, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11101517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11101517</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11101517[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/emboj/19.23.6440" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11101517">Tyson and Stirling (2000)</a> identified human SIL1. The deduced protein contains 461 amino acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11101517" 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 an ATPase-defective rodent Bip mutant as bait in a yeast 2-hybrid screen of a liver cDNA library, followed by database screening, <a href="#5" class="mim-tip-reference" title="Chung, K. T., Shen, Y., Hendershot, L. M. <strong>BAP, a mammalian BiP-associated protein, is a nucleotide exchange factor that regulates the ATPase activity of BiP.</strong> J. Biol. Chem. 277: 47557-47563, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12356756/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12356756</a>] [<a href="https://doi.org/10.1074/jbc.M208377200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12356756">Chung et al. (2002)</a> cloned SIL1, which they called BAP. The deduced 461-amino acid protein contains an N-terminal ER targeting sequence, 2 putative N-glycosylation sites, and a C-terminal ER retention signal. BAP mRNA contains 2 polyadenylation sequences. BAP shares 29% homology with Hsp70-binding protein-1 (HSPBP1; <a href="/entry/612939">612939</a>), which inhibits the ATPase activity of Hsp70 (see <a href="/entry/140550">140550</a>). Northern blot analysis detected a 1.8-kb transcript in all tissues examined, with highest levels in liver, placenta, and kidney. Immunolocalization found epitope-tagged BAP colocalized with endogenous GRP94 (<a href="/entry/191175">191175</a>) in the ER of transfected COS-1 cells. Western blot analysis and endoglycosidase treatment revealed that endogenous BAP is an N-linked glycoprotein with an apparent molecular mass of about 54 kD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12356756" 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="#11" class="mim-tip-reference" title="Takahata, T., Yamada, K., Yamada, Y., Ono, S., Kinoshita, A., Matsuzaka, T., Yoshiura,K., Kitaoka, T. <strong>Novel mutations in the SIL1 gene in a Japanese pedigree with the Marinesco-Sjogren syndrome.</strong> J. Hum. Genet. 55: 142-146, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20111056/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20111056</a>] [<a href="https://doi.org/10.1038/jhg.2009.141" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20111056">Takahata et al. (2010)</a> stated that the SIL1 gene contains 10 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20111056" 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="#11" class="mim-tip-reference" title="Takahata, T., Yamada, K., Yamada, Y., Ono, S., Kinoshita, A., Matsuzaka, T., Yoshiura,K., Kitaoka, T. <strong>Novel mutations in the SIL1 gene in a Japanese pedigree with the Marinesco-Sjogren syndrome.</strong> J. Hum. Genet. 55: 142-146, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20111056/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20111056</a>] [<a href="https://doi.org/10.1038/jhg.2009.141" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20111056">Takahata et al. (2010)</a> noted that the SIL1 gene maps to chromosome 5q31. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20111056" 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="#12" class="mim-tip-reference" title="Tyson, J. R., Stirling, C. J. <strong>LHS1 and SIL1 provide a lumenal function that is essential for protein translocation into the endoplasmic reticulum.</strong> EMBO J. 19: 6440-6452, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11101517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11101517</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11101517[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/emboj/19.23.6440" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11101517">Tyson and Stirling (2000)</a> determined that yeast Sil1 interacts directly with the ATPase domain of Bip. They found that upregulation of Sil1 was associated with the constitutively induced unfolded protein response resulting from deletion of Lhs1, an ER resident heat shock protein homologous to ORP150 (HYOU1; <a href="/entry/601746">601746</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11101517" 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 Northern blot analysis, <a href="#5" class="mim-tip-reference" title="Chung, K. T., Shen, Y., Hendershot, L. M. <strong>BAP, a mammalian BiP-associated protein, is a nucleotide exchange factor that regulates the ATPase activity of BiP.</strong> J. Biol. Chem. 277: 47557-47563, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12356756/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12356756</a>] [<a href="https://doi.org/10.1074/jbc.M208377200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12356756">Chung et al. (2002)</a> detected expression of BAP in the same tissues that express BIP. In vitro binding assays between BAP, wildtype rodent Bip, and ATPase domain mutants of rodent Bip showed that BAP bound more stably to the mutants than to wildtype Bip. BAP stimulated the ATPase activity of BIP 2-fold, and addition of both BAP and the ER protein ERDJ4 (DNAJB9; <a href="/entry/602634">602634</a>) stimulated the ATPase activity of BIP 4-fold. <a href="#5" class="mim-tip-reference" title="Chung, K. T., Shen, Y., Hendershot, L. M. <strong>BAP, a mammalian BiP-associated protein, is a nucleotide exchange factor that regulates the ATPase activity of BiP.</strong> J. Biol. Chem. 277: 47557-47563, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12356756/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12356756</a>] [<a href="https://doi.org/10.1074/jbc.M208377200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12356756">Chung et al. (2002)</a> concluded that BAP is a nucleotide exchange factor for BIP. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12356756" 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>Marinesco-Sjogren syndrome (MSS; <a href="/entry/248800">248800</a>) is an autosomal recessive disorder characterized by cerebellar ataxia, progressive myopathy, and cataracts. <a href="#3" class="mim-tip-reference" title="Anttonen, A.-K., Mahjneh, I., Hamalainen, R. H., Lagier-Tourenne, C., Kopra, O., Waris, L., Anttonen, M., Joensuu, T., Kalimo, H., Paetau, A., Tranebjaerg, L., Chaigne, D., Koenig, M., Eeg-Olofsson, O., Udd, B., Somer, M., Somer, H., Lehesjoki, A.-E. <strong>The gene disrupted in Marinesco-Sjogren syndrome encodes SIL1, an HSPA5 cochaperone.</strong> Nature Genet. 37: 1309-1311, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16282978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16282978</a>] [<a href="https://doi.org/10.1038/ng1677" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16282978">Anttonen et al. (2005)</a> identified mutations in the SIL1 gene in 8 families with MSS. The finding of mutations in the SIL1 gene in affected individuals and the similar spatial and temporal patterns of tissue expression of SIL1 and HSPA5, the heat-shock protein-70 (HSP70) chaperone for which SIL1 is a nucleotide exchange factor, suggested that disturbed SIL1-HSPA5 interaction and protein folding is the primary pathology in Marinesco-Sjogren syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16282978" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Senderek, J., Krieger, M., Stendel, C., Bergmann, C., Moser, M., Breitbach-Faller, N., Rudnik-Schoneborn, S., Blaschek, A., Wolf, N. I., Harting, I., North, K., Smith, J., and 13 others. <strong>Mutations in SIL1 cause Marinesco-Sjogren syndrome, a cerebellar ataxia with cataract and myopathy.</strong> Nature Genet. 37: 1312-1314, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16282977/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16282977</a>] [<a href="https://doi.org/10.1038/ng1678" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16282977">Senderek et al. (2005)</a> identified the gene encoding the ER resident protein SIL1 in the 2.8-Mb critical region for the MSS phenotype. They noted that SIL1 is ubiquitously expressed, and they confirmed its expression in tissues targeted by MSS. They proceeded to identify homozygous SIL1 coding sequence variants in 3 affected individuals. They also discovered sequence variants on both alleles in 2 additional consanguineous families, in 2 affected sib pairs from 2 nonconsanguineous families, and in an apparently isolated case. <a href="#10" class="mim-tip-reference" title="Senderek, J., Krieger, M., Stendel, C., Bergmann, C., Moser, M., Breitbach-Faller, N., Rudnik-Schoneborn, S., Blaschek, A., Wolf, N. I., Harting, I., North, K., Smith, J., and 13 others. <strong>Mutations in SIL1 cause Marinesco-Sjogren syndrome, a cerebellar ataxia with cataract and myopathy.</strong> Nature Genet. 37: 1312-1314, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16282977/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16282977</a>] [<a href="https://doi.org/10.1038/ng1678" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16282977">Senderek et al. (2005)</a> suggested that there are several reasons why loss of functional SIL1 could lead to a multisystem disorder like MSS. In mammalian cells, most secretory pathway proteins enter the ER cotranslationally through multiprotein complexes called 'translocons.' Chaperone GRP78, also called HSPA5 and BIP, regulates translocon gating at the ER membrane in an ATP-dependent manner. As SIL1 promotes BiP ATP-ADP exchange, reduction of SIL1 levels could affect translocon gating, resulting in decreased ER protein synthesis. Thus, MSS may be a disorder of protein biosynthesis or processing in the ER. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16282977" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of 5 families with Marinesco-Sjogren syndrome, <a href="#4" class="mim-tip-reference" title="Anttonen, A.-K., Siintola, E., Tranebjaerg, L., Iwata, N. K., Bijlsma, E. K., Meguro, H., Ichikawa, Y., Goto, J., Kopra, O., Lehesjoki, A.-E. <strong>Novel SIL1 mutations and exclusion of functional candidate genes in Marinesco-Sjogren syndrome.</strong> Europ. J. Hum. Genet. 16: 961-969, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18285827/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18285827</a>] [<a href="https://doi.org/10.1038/ejhg.2008.22" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18285827">Anttonen et al. (2008)</a> identified 4 novel homozygous mutations in the SIL1 gene (see, e.g., <a href="#0007">608005.0007</a> and <a href="#0008">608005.0008</a>). All had the classic features of cerebellar atrophy and ataxia, cataracts, mental retardation, and some form of myopathy though severity varied somewhat. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18285827" 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 Japanese sibs with Marinesco-Sjogren syndrome, <a href="#11" class="mim-tip-reference" title="Takahata, T., Yamada, K., Yamada, Y., Ono, S., Kinoshita, A., Matsuzaka, T., Yoshiura,K., Kitaoka, T. <strong>Novel mutations in the SIL1 gene in a Japanese pedigree with the Marinesco-Sjogren syndrome.</strong> J. Hum. Genet. 55: 142-146, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20111056/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20111056</a>] [<a href="https://doi.org/10.1038/jhg.2009.141" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20111056">Takahata et al. (2010)</a> identified compound heterozygosity for 2 deletions in the SIL1 gene: a 5-bp deletion (598delGAAGA; <a href="#0009">608005.0009</a>) and a 58-kb deletion (<a href="#0010">608005.0010</a>) both in exon 6. Each unaffected parent was heterozygous for 1 of the deletions. The 58-kb deletion was not detected by the standard PCR sequencing protocol, and was only found after array comparative genomic hybridization and quantitative PCR analysis. <a href="#11" class="mim-tip-reference" title="Takahata, T., Yamada, K., Yamada, Y., Ono, S., Kinoshita, A., Matsuzaka, T., Yoshiura,K., Kitaoka, T. <strong>Novel mutations in the SIL1 gene in a Japanese pedigree with the Marinesco-Sjogren syndrome.</strong> J. Hum. Genet. 55: 142-146, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20111056/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20111056</a>] [<a href="https://doi.org/10.1038/jhg.2009.141" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20111056">Takahata et al. (2010)</a> suggested that some MSS patients in whom mutations are not found should be screened for larger deletions in the SIL1 gene. All 3 patients had cataracts, ataxia, hypotonia, myopathy, spasticity, mental retardation, and skeletal deformities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20111056" 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 proteomics studies in fibroblasts from 2 patients with Marinesco-Sjogren syndrome, <a href="#7" class="mim-tip-reference" title="Hathazi, D., Cox, D., D'Amico, A., Tasca, G., Charlton, R., Carlier, R. Y., Baumann, J., Kollipara, L., Zahedi, R. P., Feldmann, I., Deleuze, J. F., Torella, A., and 16 others. <strong>INPP5K and SIL1 associated pathologies with overlapping clinical phenotypes converge through dysregulation of PHGDH.</strong> Brain 144: 2427-2442, 2021. Note: Erratum: Brain 147: e62, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33792664/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33792664</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33792664[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/brain/awab133" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33792664">Hathazi et al. (2021)</a> demonstrated decreased expression of PHGDH (<a href="/entry/606879">606879</a>) compared to controls. Fibroblasts from the 2 patients showed a 20% increase in cell viability when grown with serine supplementation compared to non-supplemented cells. <a href="#7" class="mim-tip-reference" title="Hathazi, D., Cox, D., D'Amico, A., Tasca, G., Charlton, R., Carlier, R. Y., Baumann, J., Kollipara, L., Zahedi, R. P., Feldmann, I., Deleuze, J. F., Torella, A., and 16 others. <strong>INPP5K and SIL1 associated pathologies with overlapping clinical phenotypes converge through dysregulation of PHGDH.</strong> Brain 144: 2427-2442, 2021. Note: Erratum: Brain 147: e62, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33792664/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33792664</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33792664[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/brain/awab133" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33792664">Hathazi et al. (2021)</a> hypothesized that decreased PHGDH expression is associated with dysregulation in serine metabolism and may contribute to the neurologic phenotype of MSS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33792664" 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>Endoplasmic reticulum chaperones and ER stress have been implicated in the pathogenesis of neurodegenerative disorders, such as Alzheimer (<a href="/entry/104300">104300</a>) and Parkinson (<a href="/entry/168600">168600</a>) diseases. <a href="#13" class="mim-tip-reference" title="Zhao, L., Longo-Guess, C., Harris, B. S., Lee, J.-W., Ackerman, S. L. <strong>Protein accumulation and neurodegeneration in the woozy mutant mouse is caused by disruption of SIL1, a cochaperone of BiP.</strong> Nature Genet. 37: 974-979, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16116427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16116427</a>] [<a href="https://doi.org/10.1038/ng1620" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16116427">Zhao et al. (2005)</a> established a direct in vivo link between ER dysfunction and neurodegeneration. They showed that mice homozygous with respect to the 'woozy' (wz) mutation develop adult-onset ataxia with cerebellar Purkinje cell loss. Affected cells have intracellular protein accumulations reminiscent of protein inclusions in both the ER and the nucleus. In addition, upregulation of the unfolded protein response, suggestive of ER stress, occurs in mutant Purkinje cells. <a href="#13" class="mim-tip-reference" title="Zhao, L., Longo-Guess, C., Harris, B. S., Lee, J.-W., Ackerman, S. L. <strong>Protein accumulation and neurodegeneration in the woozy mutant mouse is caused by disruption of SIL1, a cochaperone of BiP.</strong> Nature Genet. 37: 974-979, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16116427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16116427</a>] [<a href="https://doi.org/10.1038/ng1620" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16116427">Zhao et al. (2005)</a> reported that the wz mutation disrupts the gene Sil1, which encodes an adenine nucleotide exchange factor of BiP (HSPA5; <a href="/entry/138120">138120</a>), a crucial ER chaperone. The finding provided evidence that perturbation of ER chaperone function in terminally differentiated neurons leads to protein accumulation, ER stress, and subsequent neurodegeneration. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16116427" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Zhao, L., Rosales, C., Seburn, K., Ron, D., Ackerman, S. L. <strong>Alteration of the unfolded protein response modifies neurodegeneration in a mouse model of Marinesco-Sjogren syndrome.</strong> Hum. Molec. Genet. 19: 25-35, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19801575/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19801575</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19801575[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddp464" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19801575">Zhao et al. (2010)</a> reported that overexpression of Hyou1 (<a href="/entry/601746">601746</a>), an exchange factor that works in parallel to Sil1, prevented ER stress and rescued neurodegeneration in Sil1 -/- mice, whereas decreasing expression of Hyou1 exacerbated these phenotypes. In addition, loss of Dnajc3 (<a href="/entry/601184">601184</a>), a cochaperone that promotes ATP hydrolysis by BiP, ameliorated ER stress and neurodegeneration in Sil1 -/- mice. <a href="#14" class="mim-tip-reference" title="Zhao, L., Rosales, C., Seburn, K., Ron, D., Ackerman, S. L. <strong>Alteration of the unfolded protein response modifies neurodegeneration in a mouse model of Marinesco-Sjogren syndrome.</strong> Hum. Molec. Genet. 19: 25-35, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19801575/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19801575</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19801575[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddp464" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19801575">Zhao et al. (2010)</a> suggested that alterations in the nucleotide exchange cycle of BiP may cause ER stress and neurodegeneration in Sil1 -/- mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19801575" 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 all Finnish individuals with Marinesco-Sjogren syndrome (MSS; <a href="/entry/248800">248800</a>), <a href="#3" class="mim-tip-reference" title="Anttonen, A.-K., Mahjneh, I., Hamalainen, R. H., Lagier-Tourenne, C., Kopra, O., Waris, L., Anttonen, M., Joensuu, T., Kalimo, H., Paetau, A., Tranebjaerg, L., Chaigne, D., Koenig, M., Eeg-Olofsson, O., Udd, B., Somer, M., Somer, H., Lehesjoki, A.-E. <strong>The gene disrupted in Marinesco-Sjogren syndrome encodes SIL1, an HSPA5 cochaperone.</strong> Nature Genet. 37: 1309-1311, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16282978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16282978</a>] [<a href="https://doi.org/10.1038/ng1677" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16282978">Anttonen et al. (2005)</a> found a 4-nucleotide duplication, 506_509dupAAGA, in exon 6 of the SIL1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16282978" 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 5-year-old Turkish male, the offspring of consanguineous parents, with Marinesco-Sjogren syndrome (MSS; <a href="/entry/248800">248800</a>), <a href="#10" class="mim-tip-reference" title="Senderek, J., Krieger, M., Stendel, C., Bergmann, C., Moser, M., Breitbach-Faller, N., Rudnik-Schoneborn, S., Blaschek, A., Wolf, N. I., Harting, I., North, K., Smith, J., and 13 others. <strong>Mutations in SIL1 cause Marinesco-Sjogren syndrome, a cerebellar ataxia with cataract and myopathy.</strong> Nature Genet. 37: 1312-1314, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16282977/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16282977</a>] [<a href="https://doi.org/10.1038/ng1678" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16282977">Senderek et al. (2005)</a> found homozygosity for a splice site mutation in intron 6 of the SIL1 gene, 645+1G-A, which resulted in skipping of exon 6. Cataracts had been diagnosed at the age of 4.5 years. Ataxia, hypotonia, short stature, cerebellar atrophy, myopathic EMG, and myopathic biopsy showing membranous structure associated with myonuclei were features. <a href="#10" class="mim-tip-reference" title="Senderek, J., Krieger, M., Stendel, C., Bergmann, C., Moser, M., Breitbach-Faller, N., Rudnik-Schoneborn, S., Blaschek, A., Wolf, N. I., Harting, I., North, K., Smith, J., and 13 others. <strong>Mutations in SIL1 cause Marinesco-Sjogren syndrome, a cerebellar ataxia with cataract and myopathy.</strong> Nature Genet. 37: 1312-1314, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16282977/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16282977</a>] [<a href="https://doi.org/10.1038/ng1678" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16282977">Senderek et al. (2005)</a> generated a putative model of the SIL1-BIP (<a href="/entry/138120">138120</a>) interaction, which suggested that SIL1 exons 6 and 9 have a key role in associating with BIP. Thus the mutants that lack exons 6 or 9, or both, would be expected to be defective in binding to BIP. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16282977" 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 2 Swedish individuals with a Finnish paternal ancestor who were affected with Marinesco-Sjogren syndrome (MSS; <a href="/entry/248800">248800</a>), <a href="#3" class="mim-tip-reference" title="Anttonen, A.-K., Mahjneh, I., Hamalainen, R. H., Lagier-Tourenne, C., Kopra, O., Waris, L., Anttonen, M., Joensuu, T., Kalimo, H., Paetau, A., Tranebjaerg, L., Chaigne, D., Koenig, M., Eeg-Olofsson, O., Udd, B., Somer, M., Somer, H., Lehesjoki, A.-E. <strong>The gene disrupted in Marinesco-Sjogren syndrome encodes SIL1, an HSPA5 cochaperone.</strong> Nature Genet. 37: 1309-1311, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16282978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16282978</a>] [<a href="https://doi.org/10.1038/ng1677" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16282978">Anttonen et al. (2005)</a> found compound heterozygosity for 2 mutations in the SIL1 gene: the universal Finnish mutation (<a href="#0001">608005.0001</a>) and a donor splice site mutation in intron 6, 645+2T-C. RT-PCR analysis of SIL1 from lymphocyte RNA showed that the duplication mutant transcript was of the expected length, whereas 2 shorter variants were expressed from the splice site mutated allele. In the shorter of these, which was expressed at higher levels, exon 6 was skipped, predicting an in-frame deletion of 64 amino acids. In the longer variant, a cryptic splice site in exon 6 was used, predicting an in-frame deletion of 30 amino acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16282978" 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> rs119456965 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119456965;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/rs119456965?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=rs119456965" 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=rs119456965" 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 14-year-old Iranian female, the offspring of consanguineous parents, with Marinesco-Sjogren syndrome (MSS; <a href="/entry/248800">248800</a>), <a href="#10" class="mim-tip-reference" title="Senderek, J., Krieger, M., Stendel, C., Bergmann, C., Moser, M., Breitbach-Faller, N., Rudnik-Schoneborn, S., Blaschek, A., Wolf, N. I., Harting, I., North, K., Smith, J., and 13 others. <strong>Mutations in SIL1 cause Marinesco-Sjogren syndrome, a cerebellar ataxia with cataract and myopathy.</strong> Nature Genet. 37: 1312-1314, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16282977/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16282977</a>] [<a href="https://doi.org/10.1038/ng1678" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16282977">Senderek et al. (2005)</a> found a homozygous nonsense mutation in the SIL gene, arg111 to stop (R111X), due to a change at nucleotide 331 in exon 4 from C to T. The girl had congenital cataracts, ataxia, hypotonia, psychomotor delay, short stature, skeletal deformities, hypogonadism, elevated serum creatine kinase, cerebellar atrophy, myopathic biopsy and EMG, and membranous structure associated with myonuclei. The R111X mutation was also found in homozygous form in Turkish sisters, aged 38 and 16 years. Cataracts had been diagnosed at the age of 4 years in each of them. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16282977" 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>The R111X mutation was described in a Turkish family with MSS by <a href="#3" class="mim-tip-reference" title="Anttonen, A.-K., Mahjneh, I., Hamalainen, R. H., Lagier-Tourenne, C., Kopra, O., Waris, L., Anttonen, M., Joensuu, T., Kalimo, H., Paetau, A., Tranebjaerg, L., Chaigne, D., Koenig, M., Eeg-Olofsson, O., Udd, B., Somer, M., Somer, H., Lehesjoki, A.-E. <strong>The gene disrupted in Marinesco-Sjogren syndrome encodes SIL1, an HSPA5 cochaperone.</strong> Nature Genet. 37: 1309-1311, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16282978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16282978</a>] [<a href="https://doi.org/10.1038/ng1677" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16282978">Anttonen et al. (2005)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16282978" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Aguglia, U., Annesi, G., Pasquinelli, G., Spadafora, P., Gambardella, A., Annesi, F., Pasqua, A. A., Cavalcanti, F., Crescibene, L., Bagala, A., Bono, F., Oliveri, R. L., Valentino, P., Zappia, M., Quattrone, A. <strong>Vitamin E deficiency due to chylomicron retention disease in Marinesco-Sjogren syndrome.</strong> Ann. Neurol. 47: 260-264, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10665502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10665502</a>]" pmid="10665502">Aguglia et al. (2000)</a> reported 2 Italian brothers who had MSS and chylomicron retention disease (CMRD; <a href="/entry/246700">246700</a>). In these patients, <a href="#8" class="mim-tip-reference" title="Jones, B., Jones, E. L., Bonney, S. A., Patel, H. N., Mensenkamp, A. R., Eichenbaum-Voline, S., Rudling, M., Myrdal, U., Annesi, G., Naik, S., Meadows, N., Quattrone, A., and 9 others. <strong>Mutations in a Sar1 GTPase of COPII vesicles are associated with lipid absorption disorders.</strong> Nature Genet. 34: 29-31, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12692552/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12692552</a>] [<a href="https://doi.org/10.1038/ng1145" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12692552">Jones et al. (2003)</a> identified a mutation in the SAR1B gene (<a href="/entry/607690#0006">607690.0006</a>), responsible for CMRD, and <a href="#2" class="mim-tip-reference" title="Annesi, G., Aguglia, U., Tarantino, P., Annesi, F., De Marco, E. V., Civitelli, D., Torroni, A., Quattrone, A. <strong>SIL1 and SARA2 mutations in Marinesco-Sjogren and chylomicron retention disease. (Letter)</strong> Clin. Genet. 71: 288-289, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17309654/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17309654</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00759.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17309654">Annesi et al. (2007)</a> identified an R111X mutation in the SIL1 gene, responsible for MSS. The findings indicated that the patients had 2 distinct diseases due to mutations in 2 different genes, rather than defects in a single gene leading to both disorders. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10665502+12692552+17309654" 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 an 11-year-old Bosnian male, born of consanguineous parents, with Marinesco-Sjogren syndrome (MSS; <a href="/entry/248800">248800</a>), <a href="#10" class="mim-tip-reference" title="Senderek, J., Krieger, M., Stendel, C., Bergmann, C., Moser, M., Breitbach-Faller, N., Rudnik-Schoneborn, S., Blaschek, A., Wolf, N. I., Harting, I., North, K., Smith, J., and 13 others. <strong>Mutations in SIL1 cause Marinesco-Sjogren syndrome, a cerebellar ataxia with cataract and myopathy.</strong> Nature Genet. 37: 1312-1314, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16282977/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16282977</a>] [<a href="https://doi.org/10.1038/ng1678" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16282977">Senderek et al. (2005)</a> found homozygosity for a donor splice site mutation of intron 9 of the SIL1 gene, 1029+1G-A, that resulted in skipping of exon 9. Congenital cataracts, ataxia, hypotonia, psychomotor delay, short stature, cerebellar atrophy, and myopathic EMG and biopsy were described. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16282977" 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">rs119456966 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119456966;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=rs119456966" 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=rs119456966" 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=RCV000002745 OR RCV000082150" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002745, RCV000082150" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002745...</a>
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<p>In 4 affected members of 2 separate sibships in a consanguineous Egyptian family with Marinesco-Sjogren syndrome (MSS; <a href="/entry/248800">248800</a>), <a href="#9" class="mim-tip-reference" title="Karim, M. A., Parsian, A. J., Cleves, M. A., Bracey, J., Elsayed, M. S., Elsobky, E., Parsian, A. <strong>A novel mutation in BAP/SIL1 gene causes Marinesco-Sjogren syndrome in an extended pedigree. (Letter)</strong> Clin. Genet. 70: 420-423, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17026626/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17026626</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2006.00695.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17026626">Karim et al. (2006)</a> found a homozygous C-to-T transition at nucleotide 1312 in exon 10 of the SIL1 gene, resulting in a glutamine to stop codon change at position 438 (Q438X). A curious feature in this family was the lack of cerebellar ataxia in a 25-year-old male and 19-year-old female who were sibs of the mother of 7- and 9-year-old females with full expression of Marinesco-Sjogren syndrome. The older patients had delayed physical and mental development, mental retardation, progressive muscle weakness, hypotonia of legs, and cataract. The male showed hypogonadism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17026626" 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> rs119456967 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119456967;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/rs119456967?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=rs119456967" 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=rs119456967" 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=RCV000002746" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002746" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002746</a>
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<p>In 2 Japanese sibs, born of consanguineous parents, with Marinesco-Sjogren syndrome (MSS; <a href="/entry/248800">248800</a>), <a href="#4" class="mim-tip-reference" title="Anttonen, A.-K., Siintola, E., Tranebjaerg, L., Iwata, N. K., Bijlsma, E. K., Meguro, H., Ichikawa, Y., Goto, J., Kopra, O., Lehesjoki, A.-E. <strong>Novel SIL1 mutations and exclusion of functional candidate genes in Marinesco-Sjogren syndrome.</strong> Europ. J. Hum. Genet. 16: 961-969, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18285827/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18285827</a>] [<a href="https://doi.org/10.1038/ejhg.2008.22" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18285827">Anttonen et al. (2008)</a> identified a homozygous 1370T-C transition in exon 10 of the SIL1 gene, resulting in a leu457-to-pro (L457P) substitution. One of the affected sibs had a twin brother who died soon after birth. Both brothers showed psychomotor delay and distinct cerebellar symptoms, including limb and truncal ataxia, hypotonia, and dysarthria. They also had congenital cataracts. In transfected COS-1 cells, the L457P mutant protein showed altered subcellular localization compared to the wildtype protein. The mutant protein was observed to form aggregates within the endoplasmic reticulum. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18285827" 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>.0008 MARINESCO-SJOGREN SYNDROME</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000002747" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002747" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002747</a>
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<p>In 2 Japanese sisters with Marinesco-Sjogren syndrome (MSS; <a href="/entry/248800">248800</a>), <a href="#4" class="mim-tip-reference" title="Anttonen, A.-K., Siintola, E., Tranebjaerg, L., Iwata, N. K., Bijlsma, E. K., Meguro, H., Ichikawa, Y., Goto, J., Kopra, O., Lehesjoki, A.-E. <strong>Novel SIL1 mutations and exclusion of functional candidate genes in Marinesco-Sjogren syndrome.</strong> Europ. J. Hum. Genet. 16: 961-969, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18285827/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18285827</a>] [<a href="https://doi.org/10.1038/ejhg.2008.22" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18285827">Anttonen et al. (2008)</a> identified a homozygous 1-bp duplication (936_937dupG) in exon 9 of the SIL1 gene, resulting in a frameshift and premature termination (Leu313AlafsTer39). The parents were second cousins once removed. Both sisters had bilateral cataracts, learned to walk but with unstable gait, and lost ambulation around 20 years of age. Other features included short stature, psychomotor delay, hypotonia, and cerebellar atrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18285827" 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="#6" class="mim-tip-reference" title="Hasegawa, S., Imai, K., Yoshida, K., Okuno, Y., Muramatsu, H., Shiraishi, Y., Chiba, K., Tanaka, H., Miyano, S., Kojima, S., Ogawa, S., Morio, T., Mizutani, S., Takagi, M. <strong>Whole-exome sequence analysis of ataxia telangiectasia-like phenotype.</strong> J. Neurol. Sci. 340: 86-90, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24631270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24631270</a>] [<a href="https://doi.org/10.1016/j.jns.2014.02.033" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24631270">Hasegawa et al. (2014)</a> identified a homozygous c.936_397insG mutation in a 14-month-old Japanese boy with MSS. The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. The patient had mild global developmental delay, nystagmus, cerebellar atrophy, and low serum IgG and IgA in the absence of opportunistic or recurrent infections. Studies of patient-derived lymphoblastoid cells showed markedly decreased SIL1 expression as well as increased phosphorylation of EIF2A (<a href="/entry/609234">609234</a>), indicating increased ER stress, which <a href="#6" class="mim-tip-reference" title="Hasegawa, S., Imai, K., Yoshida, K., Okuno, Y., Muramatsu, H., Shiraishi, Y., Chiba, K., Tanaka, H., Miyano, S., Kojima, S., Ogawa, S., Morio, T., Mizutani, S., Takagi, M. <strong>Whole-exome sequence analysis of ataxia telangiectasia-like phenotype.</strong> J. Neurol. Sci. 340: 86-90, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24631270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24631270</a>] [<a href="https://doi.org/10.1016/j.jns.2014.02.033" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24631270">Hasegawa et al. (2014)</a> postulated may have hampered proper assembly of immunoglobulins in the ER. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24631270" 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>.0009 MARINESCO-SJOGREN SYNDROME</strong>
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SIL1, 5-BP DEL, 598GAAGA
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000002748" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002748" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002748</a>
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<p>In 3 Japanese sibs with Marinesco-Sjogren syndrome (MSS; <a href="/entry/248800">248800</a>), <a href="#11" class="mim-tip-reference" title="Takahata, T., Yamada, K., Yamada, Y., Ono, S., Kinoshita, A., Matsuzaka, T., Yoshiura,K., Kitaoka, T. <strong>Novel mutations in the SIL1 gene in a Japanese pedigree with the Marinesco-Sjogren syndrome.</strong> J. Hum. Genet. 55: 142-146, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20111056/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20111056</a>] [<a href="https://doi.org/10.1038/jhg.2009.141" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20111056">Takahata et al. (2010)</a> identified compound heterozygosity for 2 deletions in the SIL1 gene: a 5-bp deletion (598delGAAGA) in exon 6, and a 58-kb deletion in exon 6 (<a href="#0010">608005.0010</a>). Each unaffected parent was heterozygous for 1 of the deletions. The 5-bp deletion was not detected in 80 healthy Japanese individuals. The 58-kb deletion was not detected by the PCR sequencing protocol, and was only found after array comparative genomic hybridization and quantitative PCR analysis. The breakpoints of the 58-kb deletion were in a LINE/L1 repetitive sequence in intron 5 and in a unique sequence in intron 7. <a href="#11" class="mim-tip-reference" title="Takahata, T., Yamada, K., Yamada, Y., Ono, S., Kinoshita, A., Matsuzaka, T., Yoshiura,K., Kitaoka, T. <strong>Novel mutations in the SIL1 gene in a Japanese pedigree with the Marinesco-Sjogren syndrome.</strong> J. Hum. Genet. 55: 142-146, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20111056/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20111056</a>] [<a href="https://doi.org/10.1038/jhg.2009.141" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20111056">Takahata et al. (2010)</a> suggested that some MSS patients in whom mutations are not found should be screened for larger deletions in the SIL1 gene. All 3 patients had cataracts, ataxia, hypotonia, myopathy, spasticity, mental retardation, and skeletal deformities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20111056" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0010" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0010 MARINESCO-SJOGREN SYNDROME</strong>
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SIL1, 58-KB DEL
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000002749" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002749" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002749</a>
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<p>For discussion of the 58-kb deletion in the SIL1 gene that was found in compound heterozygous state in sibs with Marinesco-Sjogren syndrome (MSS; <a href="/entry/248800">248800</a>) by <a href="#11" class="mim-tip-reference" title="Takahata, T., Yamada, K., Yamada, Y., Ono, S., Kinoshita, A., Matsuzaka, T., Yoshiura,K., Kitaoka, T. <strong>Novel mutations in the SIL1 gene in a Japanese pedigree with the Marinesco-Sjogren syndrome.</strong> J. Hum. Genet. 55: 142-146, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20111056/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20111056</a>] [<a href="https://doi.org/10.1038/jhg.2009.141" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20111056">Takahata et al. (2010)</a>, see <a href="#0009">608005.0009</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20111056" 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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<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>REFERENCES</strong>
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<a id="Aguglia2000" class="mim-anchor"></a>
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Aguglia, U., Annesi, G., Pasquinelli, G., Spadafora, P., Gambardella, A., Annesi, F., Pasqua, A. A., Cavalcanti, F., Crescibene, L., Bagala, A., Bono, F., Oliveri, R. L., Valentino, P., Zappia, M., Quattrone, A.
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<strong>Vitamin E deficiency due to chylomicron retention disease in Marinesco-Sjogren syndrome.</strong>
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Ann. Neurol. 47: 260-264, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10665502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10665502</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10665502" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="Annesi2007" class="mim-anchor"></a>
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Annesi, G., Aguglia, U., Tarantino, P., Annesi, F., De Marco, E. V., Civitelli, D., Torroni, A., Quattrone, A.
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<strong>SIL1 and SARA2 mutations in Marinesco-Sjogren and chylomicron retention disease. (Letter)</strong>
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Clin. Genet. 71: 288-289, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17309654/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17309654</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17309654" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.2007.00759.x" target="_blank">Full Text</a>]
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<a id="Anttonen2005" class="mim-anchor"></a>
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Anttonen, A.-K., Mahjneh, I., Hamalainen, R. H., Lagier-Tourenne, C., Kopra, O., Waris, L., Anttonen, M., Joensuu, T., Kalimo, H., Paetau, A., Tranebjaerg, L., Chaigne, D., Koenig, M., Eeg-Olofsson, O., Udd, B., Somer, M., Somer, H., Lehesjoki, A.-E.
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<strong>The gene disrupted in Marinesco-Sjogren syndrome encodes SIL1, an HSPA5 cochaperone.</strong>
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Nature Genet. 37: 1309-1311, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16282978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16282978</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16282978" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng1677" target="_blank">Full Text</a>]
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<a id="Anttonen2008" class="mim-anchor"></a>
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Anttonen, A.-K., Siintola, E., Tranebjaerg, L., Iwata, N. K., Bijlsma, E. K., Meguro, H., Ichikawa, Y., Goto, J., Kopra, O., Lehesjoki, A.-E.
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<strong>Novel SIL1 mutations and exclusion of functional candidate genes in Marinesco-Sjogren syndrome.</strong>
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Europ. J. Hum. Genet. 16: 961-969, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18285827/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18285827</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18285827" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ejhg.2008.22" target="_blank">Full Text</a>]
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Chung, K. T., Shen, Y., Hendershot, L. M.
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<strong>BAP, a mammalian BiP-associated protein, is a nucleotide exchange factor that regulates the ATPase activity of BiP.</strong>
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J. Biol. Chem. 277: 47557-47563, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12356756/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12356756</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12356756" 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.M208377200" target="_blank">Full Text</a>]
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<a id="Hasegawa2014" class="mim-anchor"></a>
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Hasegawa, S., Imai, K., Yoshida, K., Okuno, Y., Muramatsu, H., Shiraishi, Y., Chiba, K., Tanaka, H., Miyano, S., Kojima, S., Ogawa, S., Morio, T., Mizutani, S., Takagi, M.
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<strong>Whole-exome sequence analysis of ataxia telangiectasia-like phenotype.</strong>
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J. Neurol. Sci. 340: 86-90, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24631270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24631270</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24631270" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.jns.2014.02.033" target="_blank">Full Text</a>]
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<a id="Hathazi2021" class="mim-anchor"></a>
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Hathazi, D., Cox, D., D'Amico, A., Tasca, G., Charlton, R., Carlier, R. Y., Baumann, J., Kollipara, L., Zahedi, R. P., Feldmann, I., Deleuze, J. F., Torella, A., and 16 others.
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<strong>INPP5K and SIL1 associated pathologies with overlapping clinical phenotypes converge through dysregulation of PHGDH.</strong>
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Brain 144: 2427-2442, 2021. Note: Erratum: Brain 147: e62, 2024.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33792664/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33792664</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33792664[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=33792664" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/brain/awab133" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="8" class="mim-anchor"></a>
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<a id="Jones2003" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
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|
Jones, B., Jones, E. L., Bonney, S. A., Patel, H. N., Mensenkamp, A. R., Eichenbaum-Voline, S., Rudling, M., Myrdal, U., Annesi, G., Naik, S., Meadows, N., Quattrone, A., and 9 others.
|
|
<strong>Mutations in a Sar1 GTPase of COPII vesicles are associated with lipid absorption disorders.</strong>
|
|
Nature Genet. 34: 29-31, 2003.
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|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12692552/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12692552</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12692552" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng1145" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="9" class="mim-anchor"></a>
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<a id="Karim2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Karim, M. A., Parsian, A. J., Cleves, M. A., Bracey, J., Elsayed, M. S., Elsobky, E., Parsian, A.
|
|
<strong>A novel mutation in BAP/SIL1 gene causes Marinesco-Sjogren syndrome in an extended pedigree. (Letter)</strong>
|
|
Clin. Genet. 70: 420-423, 2006.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17026626/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17026626</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17026626" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.2006.00695.x" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="10" class="mim-anchor"></a>
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<a id="Senderek2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Senderek, J., Krieger, M., Stendel, C., Bergmann, C., Moser, M., Breitbach-Faller, N., Rudnik-Schoneborn, S., Blaschek, A., Wolf, N. I., Harting, I., North, K., Smith, J., and 13 others.
|
|
<strong>Mutations in SIL1 cause Marinesco-Sjogren syndrome, a cerebellar ataxia with cataract and myopathy.</strong>
|
|
Nature Genet. 37: 1312-1314, 2005.
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|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16282977/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16282977</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16282977" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng1678" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="11" class="mim-anchor"></a>
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<a id="Takahata2010" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Takahata, T., Yamada, K., Yamada, Y., Ono, S., Kinoshita, A., Matsuzaka, T., Yoshiura,K., Kitaoka, T.
|
|
<strong>Novel mutations in the SIL1 gene in a Japanese pedigree with the Marinesco-Sjogren syndrome.</strong>
|
|
J. Hum. Genet. 55: 142-146, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20111056/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20111056</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20111056" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/jhg.2009.141" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="12" class="mim-anchor"></a>
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<a id="Tyson2000" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tyson, J. R., Stirling, C. J.
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<strong>LHS1 and SIL1 provide a lumenal function that is essential for protein translocation into the endoplasmic reticulum.</strong>
|
|
EMBO J. 19: 6440-6452, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11101517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11101517</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11101517[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=11101517" 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/emboj/19.23.6440" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="13" class="mim-anchor"></a>
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<a id="Zhao2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zhao, L., Longo-Guess, C., Harris, B. S., Lee, J.-W., Ackerman, S. L.
|
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<strong>Protein accumulation and neurodegeneration in the woozy mutant mouse is caused by disruption of SIL1, a cochaperone of BiP.</strong>
|
|
Nature Genet. 37: 974-979, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16116427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16116427</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16116427" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng1620" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="14" class="mim-anchor"></a>
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<a id="Zhao2010" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zhao, L., Rosales, C., Seburn, K., Ron, D., Ackerman, S. L.
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<strong>Alteration of the unfolded protein response modifies neurodegeneration in a mouse model of Marinesco-Sjogren syndrome.</strong>
|
|
Hum. Molec. Genet. 19: 25-35, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19801575/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19801575</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19801575[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=19801575" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddp464" target="_blank">Full Text</a>]
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</p>
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</div>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Hilary J. Vernon - updated : 10/13/2022
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 9/22/2014<br>George E. Tiller - updated : 11/12/2010<br>Cassandra L. Kniffin - updated : 4/21/2010<br>Cassandra L. Kniffin - updated : 8/19/2008<br>Victor A. McKusick - updated : 9/11/2007<br>Cassandra L. Kniffin - updated : 8/29/2007<br>Victor A. McKusick - updated : 12/1/2005<br>Victor A. McKusick - updated : 9/27/2005
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Patricia A. Hartz : 7/31/2003
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 01/15/2025
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 10/13/2022<br>carol : 08/12/2020<br>carol : 09/13/2019<br>carol : 07/01/2015<br>mcolton : 6/16/2015<br>carol : 9/22/2014<br>ckniffin : 9/22/2014<br>carol : 9/19/2013<br>wwang : 11/18/2010<br>terry : 11/12/2010<br>wwang : 4/29/2010<br>ckniffin : 4/21/2010<br>mgross : 7/28/2009<br>wwang : 8/28/2008<br>ckniffin : 8/19/2008<br>alopez : 9/11/2007<br>wwang : 9/11/2007<br>ckniffin : 8/29/2007<br>wwang : 5/17/2006<br>alopez : 12/1/2005<br>terry : 12/1/2005<br>alopez : 9/28/2005<br>terry : 9/27/2005<br>terry : 7/20/2004<br>mgross : 7/31/2003
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
|
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<strong>*</strong> 608005
|
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</span>
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</h3>
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</div>
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<div>
|
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<h3>
|
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<span class="mim-font">
|
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|
|
SIL1 NUCLEOTIDE EXCHANGE FACTOR; SIL1
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
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</span>
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</p>
|
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</div>
|
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
SIL1, S. CEREVISIAE, HOMOLOG OF<br />
|
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BIP-ASSOCIATED PROTEIN; BAP
|
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</span>
|
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</h4>
|
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
|
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<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: SIL1</em></strong>
|
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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|
|
<strong>SNOMEDCT:</strong> 80734006;
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: 5q31.2
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 5:138,946,724-139,198,368 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
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</p>
|
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</div>
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<div>
|
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<br />
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
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</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
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</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
5q31.2
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Marinesco-Sjogren syndrome
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
248800
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
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</tr>
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</tbody>
|
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</table>
|
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</div>
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</div>
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<div>
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<br />
|
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</div>
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<div>
|
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|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
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|
<span class="mim-text-font">
|
|
<p>SIL1 is a resident endoplasmic reticulum (ER) glycoprotein that interacts with the ATPase domain of BIP (HSPA5; 138120) and enhances nucleotide exchange.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By searching EST databases for sequences showing similarity to yeast Sil1, Tyson and Stirling (2000) identified human SIL1. The deduced protein contains 461 amino acids. </p><p>Using an ATPase-defective rodent Bip mutant as bait in a yeast 2-hybrid screen of a liver cDNA library, followed by database screening, Chung et al. (2002) cloned SIL1, which they called BAP. The deduced 461-amino acid protein contains an N-terminal ER targeting sequence, 2 putative N-glycosylation sites, and a C-terminal ER retention signal. BAP mRNA contains 2 polyadenylation sequences. BAP shares 29% homology with Hsp70-binding protein-1 (HSPBP1; 612939), which inhibits the ATPase activity of Hsp70 (see 140550). Northern blot analysis detected a 1.8-kb transcript in all tissues examined, with highest levels in liver, placenta, and kidney. Immunolocalization found epitope-tagged BAP colocalized with endogenous GRP94 (191175) in the ER of transfected COS-1 cells. Western blot analysis and endoglycosidase treatment revealed that endogenous BAP is an N-linked glycoprotein with an apparent molecular mass of about 54 kD. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Takahata et al. (2010) stated that the SIL1 gene contains 10 exons. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Takahata et al. (2010) noted that the SIL1 gene maps to chromosome 5q31. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Tyson and Stirling (2000) determined that yeast Sil1 interacts directly with the ATPase domain of Bip. They found that upregulation of Sil1 was associated with the constitutively induced unfolded protein response resulting from deletion of Lhs1, an ER resident heat shock protein homologous to ORP150 (HYOU1; 601746). </p><p>By Northern blot analysis, Chung et al. (2002) detected expression of BAP in the same tissues that express BIP. In vitro binding assays between BAP, wildtype rodent Bip, and ATPase domain mutants of rodent Bip showed that BAP bound more stably to the mutants than to wildtype Bip. BAP stimulated the ATPase activity of BIP 2-fold, and addition of both BAP and the ER protein ERDJ4 (DNAJB9; 602634) stimulated the ATPase activity of BIP 4-fold. Chung et al. (2002) concluded that BAP is a nucleotide exchange factor for BIP. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Marinesco-Sjogren syndrome (MSS; 248800) is an autosomal recessive disorder characterized by cerebellar ataxia, progressive myopathy, and cataracts. Anttonen et al. (2005) identified mutations in the SIL1 gene in 8 families with MSS. The finding of mutations in the SIL1 gene in affected individuals and the similar spatial and temporal patterns of tissue expression of SIL1 and HSPA5, the heat-shock protein-70 (HSP70) chaperone for which SIL1 is a nucleotide exchange factor, suggested that disturbed SIL1-HSPA5 interaction and protein folding is the primary pathology in Marinesco-Sjogren syndrome. </p><p>Senderek et al. (2005) identified the gene encoding the ER resident protein SIL1 in the 2.8-Mb critical region for the MSS phenotype. They noted that SIL1 is ubiquitously expressed, and they confirmed its expression in tissues targeted by MSS. They proceeded to identify homozygous SIL1 coding sequence variants in 3 affected individuals. They also discovered sequence variants on both alleles in 2 additional consanguineous families, in 2 affected sib pairs from 2 nonconsanguineous families, and in an apparently isolated case. Senderek et al. (2005) suggested that there are several reasons why loss of functional SIL1 could lead to a multisystem disorder like MSS. In mammalian cells, most secretory pathway proteins enter the ER cotranslationally through multiprotein complexes called 'translocons.' Chaperone GRP78, also called HSPA5 and BIP, regulates translocon gating at the ER membrane in an ATP-dependent manner. As SIL1 promotes BiP ATP-ADP exchange, reduction of SIL1 levels could affect translocon gating, resulting in decreased ER protein synthesis. Thus, MSS may be a disorder of protein biosynthesis or processing in the ER. </p><p>In affected members of 5 families with Marinesco-Sjogren syndrome, Anttonen et al. (2008) identified 4 novel homozygous mutations in the SIL1 gene (see, e.g., 608005.0007 and 608005.0008). All had the classic features of cerebellar atrophy and ataxia, cataracts, mental retardation, and some form of myopathy though severity varied somewhat. </p><p>In 3 Japanese sibs with Marinesco-Sjogren syndrome, Takahata et al. (2010) identified compound heterozygosity for 2 deletions in the SIL1 gene: a 5-bp deletion (598delGAAGA; 608005.0009) and a 58-kb deletion (608005.0010) both in exon 6. Each unaffected parent was heterozygous for 1 of the deletions. The 58-kb deletion was not detected by the standard PCR sequencing protocol, and was only found after array comparative genomic hybridization and quantitative PCR analysis. Takahata et al. (2010) suggested that some MSS patients in whom mutations are not found should be screened for larger deletions in the SIL1 gene. All 3 patients had cataracts, ataxia, hypotonia, myopathy, spasticity, mental retardation, and skeletal deformities. </p><p>In proteomics studies in fibroblasts from 2 patients with Marinesco-Sjogren syndrome, Hathazi et al. (2021) demonstrated decreased expression of PHGDH (606879) compared to controls. Fibroblasts from the 2 patients showed a 20% increase in cell viability when grown with serine supplementation compared to non-supplemented cells. Hathazi et al. (2021) hypothesized that decreased PHGDH expression is associated with dysregulation in serine metabolism and may contribute to the neurologic phenotype of MSS. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Endoplasmic reticulum chaperones and ER stress have been implicated in the pathogenesis of neurodegenerative disorders, such as Alzheimer (104300) and Parkinson (168600) diseases. Zhao et al. (2005) established a direct in vivo link between ER dysfunction and neurodegeneration. They showed that mice homozygous with respect to the 'woozy' (wz) mutation develop adult-onset ataxia with cerebellar Purkinje cell loss. Affected cells have intracellular protein accumulations reminiscent of protein inclusions in both the ER and the nucleus. In addition, upregulation of the unfolded protein response, suggestive of ER stress, occurs in mutant Purkinje cells. Zhao et al. (2005) reported that the wz mutation disrupts the gene Sil1, which encodes an adenine nucleotide exchange factor of BiP (HSPA5; 138120), a crucial ER chaperone. The finding provided evidence that perturbation of ER chaperone function in terminally differentiated neurons leads to protein accumulation, ER stress, and subsequent neurodegeneration. </p><p>Zhao et al. (2010) reported that overexpression of Hyou1 (601746), an exchange factor that works in parallel to Sil1, prevented ER stress and rescued neurodegeneration in Sil1 -/- mice, whereas decreasing expression of Hyou1 exacerbated these phenotypes. In addition, loss of Dnajc3 (601184), a cochaperone that promotes ATP hydrolysis by BiP, ameliorated ER stress and neurodegeneration in Sil1 -/- mice. Zhao et al. (2010) suggested that alterations in the nucleotide exchange cycle of BiP may cause ER stress and neurodegeneration in Sil1 -/- mice. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>10 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0001 MARINESCO-SJOGREN SYNDROME</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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SIL1, 4-BP DUP, 506AAGA
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<br />
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ClinVar: RCV000002740
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In all Finnish individuals with Marinesco-Sjogren syndrome (MSS; 248800), Anttonen et al. (2005) found a 4-nucleotide duplication, 506_509dupAAGA, in exon 6 of the SIL1 gene. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0002 MARINESCO-SJOGREN SYNDROME</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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SIL1, IVS6DS, G-A, +1
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<br />
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ClinVar: RCV000002741
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a 5-year-old Turkish male, the offspring of consanguineous parents, with Marinesco-Sjogren syndrome (MSS; 248800), Senderek et al. (2005) found homozygosity for a splice site mutation in intron 6 of the SIL1 gene, 645+1G-A, which resulted in skipping of exon 6. Cataracts had been diagnosed at the age of 4.5 years. Ataxia, hypotonia, short stature, cerebellar atrophy, myopathic EMG, and myopathic biopsy showing membranous structure associated with myonuclei were features. Senderek et al. (2005) generated a putative model of the SIL1-BIP (138120) interaction, which suggested that SIL1 exons 6 and 9 have a key role in associating with BIP. Thus the mutants that lack exons 6 or 9, or both, would be expected to be defective in binding to BIP. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 MARINESCO-SJOGREN SYNDROME</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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SIL1, IVS6DS, T-C, +2
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<br />
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ClinVar: RCV000002742
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</span>
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</div>
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<div>
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|
<span class="mim-text-font">
|
|
<p>In 2 Swedish individuals with a Finnish paternal ancestor who were affected with Marinesco-Sjogren syndrome (MSS; 248800), Anttonen et al. (2005) found compound heterozygosity for 2 mutations in the SIL1 gene: the universal Finnish mutation (608005.0001) and a donor splice site mutation in intron 6, 645+2T-C. RT-PCR analysis of SIL1 from lymphocyte RNA showed that the duplication mutant transcript was of the expected length, whereas 2 shorter variants were expressed from the splice site mutated allele. In the shorter of these, which was expressed at higher levels, exon 6 was skipped, predicting an in-frame deletion of 64 amino acids. In the longer variant, a cryptic splice site in exon 6 was used, predicting an in-frame deletion of 30 amino acids. </p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 MARINESCO-SJOGREN SYNDROME</strong>
|
|
</span>
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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SIL1, ARG111TER
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<br />
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|
|
SNP: rs119456965,
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gnomAD: rs119456965,
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|
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ClinVar: RCV000002743
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|
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|
|
</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 14-year-old Iranian female, the offspring of consanguineous parents, with Marinesco-Sjogren syndrome (MSS; 248800), Senderek et al. (2005) found a homozygous nonsense mutation in the SIL gene, arg111 to stop (R111X), due to a change at nucleotide 331 in exon 4 from C to T. The girl had congenital cataracts, ataxia, hypotonia, psychomotor delay, short stature, skeletal deformities, hypogonadism, elevated serum creatine kinase, cerebellar atrophy, myopathic biopsy and EMG, and membranous structure associated with myonuclei. The R111X mutation was also found in homozygous form in Turkish sisters, aged 38 and 16 years. Cataracts had been diagnosed at the age of 4 years in each of them. </p><p>The R111X mutation was described in a Turkish family with MSS by Anttonen et al. (2005). </p><p>Aguglia et al. (2000) reported 2 Italian brothers who had MSS and chylomicron retention disease (CMRD; 246700). In these patients, Jones et al. (2003) identified a mutation in the SAR1B gene (607690.0006), responsible for CMRD, and Annesi et al. (2007) identified an R111X mutation in the SIL1 gene, responsible for MSS. The findings indicated that the patients had 2 distinct diseases due to mutations in 2 different genes, rather than defects in a single gene leading to both disorders. </p>
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|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 MARINESCO-SJOGREN SYNDROME</strong>
|
|
</span>
|
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</h4>
|
|
</div>
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|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
SIL1, IVS9DS, G-A, +1
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000002744
|
|
|
|
|
|
</span>
|
|
</div>
|
|
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|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an 11-year-old Bosnian male, born of consanguineous parents, with Marinesco-Sjogren syndrome (MSS; 248800), Senderek et al. (2005) found homozygosity for a donor splice site mutation of intron 9 of the SIL1 gene, 1029+1G-A, that resulted in skipping of exon 9. Congenital cataracts, ataxia, hypotonia, psychomotor delay, short stature, cerebellar atrophy, and myopathic EMG and biopsy were described. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
|
</div>
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|
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</div>
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|
|
<div>
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|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 MARINESCO-SJOGREN SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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|
<span class="mim-text-font">
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|
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|
SIL1, GLN438TER
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|
|
<br />
|
|
|
|
SNP: rs119456966,
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|
|
|
|
|
ClinVar: RCV000002745, RCV000082150
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|
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</span>
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|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In 4 affected members of 2 separate sibships in a consanguineous Egyptian family with Marinesco-Sjogren syndrome (MSS; 248800), Karim et al. (2006) found a homozygous C-to-T transition at nucleotide 1312 in exon 10 of the SIL1 gene, resulting in a glutamine to stop codon change at position 438 (Q438X). A curious feature in this family was the lack of cerebellar ataxia in a 25-year-old male and 19-year-old female who were sibs of the mother of 7- and 9-year-old females with full expression of Marinesco-Sjogren syndrome. The older patients had delayed physical and mental development, mental retardation, progressive muscle weakness, hypotonia of legs, and cataract. The male showed hypogonadism. </p>
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|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 MARINESCO-SJOGREN SYNDROME</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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SIL1, LEU457PRO
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<br />
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|
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SNP: rs119456967,
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gnomAD: rs119456967,
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ClinVar: RCV000002746
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 Japanese sibs, born of consanguineous parents, with Marinesco-Sjogren syndrome (MSS; 248800), Anttonen et al. (2008) identified a homozygous 1370T-C transition in exon 10 of the SIL1 gene, resulting in a leu457-to-pro (L457P) substitution. One of the affected sibs had a twin brother who died soon after birth. Both brothers showed psychomotor delay and distinct cerebellar symptoms, including limb and truncal ataxia, hypotonia, and dysarthria. They also had congenital cataracts. In transfected COS-1 cells, the L457P mutant protein showed altered subcellular localization compared to the wildtype protein. The mutant protein was observed to form aggregates within the endoplasmic reticulum. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0008 MARINESCO-SJOGREN SYNDROME</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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SIL1, 1-BP DUP, 936G
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<br />
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|
|
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ClinVar: RCV000002747
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</span>
|
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In 2 Japanese sisters with Marinesco-Sjogren syndrome (MSS; 248800), Anttonen et al. (2008) identified a homozygous 1-bp duplication (936_937dupG) in exon 9 of the SIL1 gene, resulting in a frameshift and premature termination (Leu313AlafsTer39). The parents were second cousins once removed. Both sisters had bilateral cataracts, learned to walk but with unstable gait, and lost ambulation around 20 years of age. Other features included short stature, psychomotor delay, hypotonia, and cerebellar atrophy. </p><p>Hasegawa et al. (2014) identified a homozygous c.936_397insG mutation in a 14-month-old Japanese boy with MSS. The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. The patient had mild global developmental delay, nystagmus, cerebellar atrophy, and low serum IgG and IgA in the absence of opportunistic or recurrent infections. Studies of patient-derived lymphoblastoid cells showed markedly decreased SIL1 expression as well as increased phosphorylation of EIF2A (609234), indicating increased ER stress, which Hasegawa et al. (2014) postulated may have hampered proper assembly of immunoglobulins in the ER. </p>
|
|
</span>
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</div>
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<strong>.0009 MARINESCO-SJOGREN SYNDROME</strong>
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SIL1, 5-BP DEL, 598GAAGA
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ClinVar: RCV000002748
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<p>In 3 Japanese sibs with Marinesco-Sjogren syndrome (MSS; 248800), Takahata et al. (2010) identified compound heterozygosity for 2 deletions in the SIL1 gene: a 5-bp deletion (598delGAAGA) in exon 6, and a 58-kb deletion in exon 6 (608005.0010). Each unaffected parent was heterozygous for 1 of the deletions. The 5-bp deletion was not detected in 80 healthy Japanese individuals. The 58-kb deletion was not detected by the PCR sequencing protocol, and was only found after array comparative genomic hybridization and quantitative PCR analysis. The breakpoints of the 58-kb deletion were in a LINE/L1 repetitive sequence in intron 5 and in a unique sequence in intron 7. Takahata et al. (2010) suggested that some MSS patients in whom mutations are not found should be screened for larger deletions in the SIL1 gene. All 3 patients had cataracts, ataxia, hypotonia, myopathy, spasticity, mental retardation, and skeletal deformities. </p>
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<span class="mim-font">
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<strong>.0010 MARINESCO-SJOGREN SYNDROME</strong>
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SIL1, 58-KB DEL
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ClinVar: RCV000002749
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<p>For discussion of the 58-kb deletion in the SIL1 gene that was found in compound heterozygous state in sibs with Marinesco-Sjogren syndrome (MSS; 248800) by Takahata et al. (2010), see 608005.0009. </p>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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Aguglia, U., Annesi, G., Pasquinelli, G., Spadafora, P., Gambardella, A., Annesi, F., Pasqua, A. A., Cavalcanti, F., Crescibene, L., Bagala, A., Bono, F., Oliveri, R. L., Valentino, P., Zappia, M., Quattrone, A.
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<strong>Vitamin E deficiency due to chylomicron retention disease in Marinesco-Sjogren syndrome.</strong>
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Ann. Neurol. 47: 260-264, 2000.
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[PubMed: 10665502]
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</p>
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</li>
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<p class="mim-text-font">
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Annesi, G., Aguglia, U., Tarantino, P., Annesi, F., De Marco, E. V., Civitelli, D., Torroni, A., Quattrone, A.
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<strong>SIL1 and SARA2 mutations in Marinesco-Sjogren and chylomicron retention disease. (Letter)</strong>
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Clin. Genet. 71: 288-289, 2007.
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[PubMed: 17309654]
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[Full Text: https://doi.org/10.1111/j.1399-0004.2007.00759.x]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Anttonen, A.-K., Mahjneh, I., Hamalainen, R. H., Lagier-Tourenne, C., Kopra, O., Waris, L., Anttonen, M., Joensuu, T., Kalimo, H., Paetau, A., Tranebjaerg, L., Chaigne, D., Koenig, M., Eeg-Olofsson, O., Udd, B., Somer, M., Somer, H., Lehesjoki, A.-E.
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<strong>The gene disrupted in Marinesco-Sjogren syndrome encodes SIL1, an HSPA5 cochaperone.</strong>
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Nature Genet. 37: 1309-1311, 2005.
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[PubMed: 16282978]
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[Full Text: https://doi.org/10.1038/ng1677]
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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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Anttonen, A.-K., Siintola, E., Tranebjaerg, L., Iwata, N. K., Bijlsma, E. K., Meguro, H., Ichikawa, Y., Goto, J., Kopra, O., Lehesjoki, A.-E.
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<strong>Novel SIL1 mutations and exclusion of functional candidate genes in Marinesco-Sjogren syndrome.</strong>
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Europ. J. Hum. Genet. 16: 961-969, 2008.
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[PubMed: 18285827]
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[Full Text: https://doi.org/10.1038/ejhg.2008.22]
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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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Chung, K. T., Shen, Y., Hendershot, L. M.
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<strong>BAP, a mammalian BiP-associated protein, is a nucleotide exchange factor that regulates the ATPase activity of BiP.</strong>
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J. Biol. Chem. 277: 47557-47563, 2002.
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[PubMed: 12356756]
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[Full Text: https://doi.org/10.1074/jbc.M208377200]
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</p>
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</li>
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<p class="mim-text-font">
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Hasegawa, S., Imai, K., Yoshida, K., Okuno, Y., Muramatsu, H., Shiraishi, Y., Chiba, K., Tanaka, H., Miyano, S., Kojima, S., Ogawa, S., Morio, T., Mizutani, S., Takagi, M.
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<strong>Whole-exome sequence analysis of ataxia telangiectasia-like phenotype.</strong>
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J. Neurol. Sci. 340: 86-90, 2014.
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[PubMed: 24631270]
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[Full Text: https://doi.org/10.1016/j.jns.2014.02.033]
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Hathazi, D., Cox, D., D'Amico, A., Tasca, G., Charlton, R., Carlier, R. Y., Baumann, J., Kollipara, L., Zahedi, R. P., Feldmann, I., Deleuze, J. F., Torella, A., and 16 others.
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<strong>INPP5K and SIL1 associated pathologies with overlapping clinical phenotypes converge through dysregulation of PHGDH.</strong>
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Brain 144: 2427-2442, 2021. Note: Erratum: Brain 147: e62, 2024.
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[PubMed: 33792664]
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[Full Text: https://doi.org/10.1093/brain/awab133]
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Jones, B., Jones, E. L., Bonney, S. A., Patel, H. N., Mensenkamp, A. R., Eichenbaum-Voline, S., Rudling, M., Myrdal, U., Annesi, G., Naik, S., Meadows, N., Quattrone, A., and 9 others.
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<strong>Mutations in a Sar1 GTPase of COPII vesicles are associated with lipid absorption disorders.</strong>
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Nature Genet. 34: 29-31, 2003.
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[PubMed: 12692552]
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[Full Text: https://doi.org/10.1038/ng1145]
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Karim, M. A., Parsian, A. J., Cleves, M. A., Bracey, J., Elsayed, M. S., Elsobky, E., Parsian, A.
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<strong>A novel mutation in BAP/SIL1 gene causes Marinesco-Sjogren syndrome in an extended pedigree. (Letter)</strong>
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Clin. Genet. 70: 420-423, 2006.
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[PubMed: 17026626]
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[Full Text: https://doi.org/10.1111/j.1399-0004.2006.00695.x]
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<p class="mim-text-font">
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Senderek, J., Krieger, M., Stendel, C., Bergmann, C., Moser, M., Breitbach-Faller, N., Rudnik-Schoneborn, S., Blaschek, A., Wolf, N. I., Harting, I., North, K., Smith, J., and 13 others.
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<strong>Mutations in SIL1 cause Marinesco-Sjogren syndrome, a cerebellar ataxia with cataract and myopathy.</strong>
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Nature Genet. 37: 1312-1314, 2005.
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[PubMed: 16282977]
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[Full Text: https://doi.org/10.1038/ng1678]
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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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Takahata, T., Yamada, K., Yamada, Y., Ono, S., Kinoshita, A., Matsuzaka, T., Yoshiura,K., Kitaoka, T.
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<strong>Novel mutations in the SIL1 gene in a Japanese pedigree with the Marinesco-Sjogren syndrome.</strong>
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J. Hum. Genet. 55: 142-146, 2010.
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[PubMed: 20111056]
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[Full Text: https://doi.org/10.1038/jhg.2009.141]
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<li>
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<p class="mim-text-font">
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Tyson, J. R., Stirling, C. J.
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<strong>LHS1 and SIL1 provide a lumenal function that is essential for protein translocation into the endoplasmic reticulum.</strong>
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EMBO J. 19: 6440-6452, 2000.
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[PubMed: 11101517]
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[Full Text: https://doi.org/10.1093/emboj/19.23.6440]
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<p class="mim-text-font">
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Zhao, L., Longo-Guess, C., Harris, B. S., Lee, J.-W., Ackerman, S. L.
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<strong>Protein accumulation and neurodegeneration in the woozy mutant mouse is caused by disruption of SIL1, a cochaperone of BiP.</strong>
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Nature Genet. 37: 974-979, 2005.
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[PubMed: 16116427]
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[Full Text: https://doi.org/10.1038/ng1620]
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<li>
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<p class="mim-text-font">
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Zhao, L., Rosales, C., Seburn, K., Ron, D., Ackerman, S. L.
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<strong>Alteration of the unfolded protein response modifies neurodegeneration in a mouse model of Marinesco-Sjogren syndrome.</strong>
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Hum. Molec. Genet. 19: 25-35, 2010.
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[PubMed: 19801575]
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[Full Text: https://doi.org/10.1093/hmg/ddp464]
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<p>
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Thank you in advance for your generous support, <br />
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Ada Hamosh, MD, MPH <br />
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Scientific Director, OMIM <br />
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