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Entry
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- *606976 - COMPONENT OF OLIGOMERIC GOLGI COMPLEX 4; COG4
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- OMIM
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<p>
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<span class="h4">*606976</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#biochemicalFeatures">Biochemical Features</a>
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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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<a href="#molecularGenetics">Molecular Genetics</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/606976">Table View</a>
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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 role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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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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<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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<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=ENSG00000103051;t=ENST00000323786" 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=25839" 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=606976" 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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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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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=ENSG00000103051;t=ENST00000323786" 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_001195139,NM_001365426,NM_015386,NR_158212" 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_015386" 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=606976" 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=08444&isoform_id=08444_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/COG4" 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/4884130,10434521,10439300,12653997,21756080,21907904,39644744,39645057,40226121,48734815,118498354,119572191,119572192,119572193,119572194,119572195,119572196,119572197,119572198,124504238,124504644,194375656,194387168,311033464,1562203527,1562203529" 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/Q9H9E3" 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=25839" 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=ENSG00000103051;t=ENST00000323786" 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=COG4" 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=COG4" 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+25839" 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/COG4" 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:25839" 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/25839" 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=chr16&hgg_gene=ENST00000323786.10&hgg_start=70480567&hgg_end=70523554&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:18620" 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:18620" 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/cog4" 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=606976[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=606976[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/COG4/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000103051" 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=COG4" 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=COG4" 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=COG4" 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=COG4&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/PA38603" 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:18620" 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/FBgn0032258.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:2142808" 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/COG4#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:2142808" 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/25839/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=25839" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00021784;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-060312-33" 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://reactome.org/content/query?q=COG4&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> 718751000<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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606976
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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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COMPONENT OF OLIGOMERIC GOLGI COMPLEX 4; COG4
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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">
|
|
COD1, S. CEREVISIAE, HOMOLOG OF; COD1
|
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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=COG4" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">COG4</a></em></strong>
|
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</span>
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</p>
|
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
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<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/16/607?start=-3&limit=10&highlight=607">16q22.1</a>
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr16:70480567-70523554&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'})">16:70,480,567-70,523,554</a> </span>
|
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</em>
|
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
|
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</p>
|
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</div>
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<div>
|
|
<br />
|
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</div>
|
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<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=613489,618150" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
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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="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/16/607?start=-3&limit=10&highlight=607">
|
|
16q22.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Congenital disorder of glycosylation, type IIj
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/613489"> 613489 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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|
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</span>
|
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</td>
|
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<td>
|
|
<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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|
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|
|
|
|
</tr>
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<tr>
|
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<td>
|
|
<span class="mim-font">
|
|
Saul-Wilson syndrome
|
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|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/618150"> 618150 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
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<p>Multiprotein complexes are key determinants of Golgi apparatus structure and its capacity for intracellular transport and glycoprotein modification. Several complexes have been identified, including the Golgi transport complex (GTC), the LDLC complex, which is involved in glycosylation reactions, and the SEC34 complex, which is involved in vesicular transport. These 3 complexes are identical and have been termed the conserved oligomeric Golgi (COG) complex, which includes COG4 (<a href="#9" class="mim-tip-reference" title="Ungar, D., Oka, T., Brittle, E. E., Vasile, E., Lupashin, V. V., Chatterton, J. E., Heuser, J. E., Krieger, M., Waters, M. G. <strong>Characterization of a mammalian Golgi-localized protein complex, COG, that is required for normal Golgi morphology and function.</strong> J. Cell Biol. 157: 405-415, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11980916/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11980916</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11980916[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/10.1083/jcb.200202016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11980916">Ungar et al., 2002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11980916" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By database searching for sequences homologous to the yeast complexed with Dor1 (COG8; <a href="/entry/606979">606979</a>) (COD) proteins, <a href="#10" class="mim-tip-reference" title="Whyte, J. R. C., Munro, S. <strong>The Sec34/35 Golgi transport complex is related to the exocyst, defining a family of complexes involved in multiple steps of membrane traffic.</strong> Dev. Cell 1: 527-537, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11703943/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11703943</a>] [<a href="https://doi.org/10.1016/s1534-5807(01)00063-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11703943">Whyte and Munro (2001)</a> identified cDNAs encoding COG4, which they called COD1, and other members of the COG complex. The deduced 785-amino acid COG4 protein contains an N-terminal coiled-coil region. Coiled-coil regions are found in all members of the COG complex and may be involved in holding the complex together or in binding other proteins involved in vesicle docking and fusion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11703943" 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 SDS-PAGE analysis of bovine brain cytosol, <a href="#9" class="mim-tip-reference" title="Ungar, D., Oka, T., Brittle, E. E., Vasile, E., Lupashin, V. V., Chatterton, J. E., Heuser, J. E., Krieger, M., Waters, M. G. <strong>Characterization of a mammalian Golgi-localized protein complex, COG, that is required for normal Golgi morphology and function.</strong> J. Cell Biol. 157: 405-415, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11980916/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11980916</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11980916[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/10.1083/jcb.200202016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11980916">Ungar et al. (2002)</a> identified the 8 subunits of the COG complex. Immunofluorescence microscopy demonstrated that COG1 (LDLB; <a href="/entry/606973">606973</a>) colocalizes with COG7 (<a href="/entry/606978">606978</a>), as well as with COG3 (<a href="/entry/606975">606975</a>) and COG5 (<a href="/entry/606821">606821</a>), with a Golgi marker in a perinuclear distribution. Immunoprecipitation analysis showed that all COG subunits interact with COG2 (LDLC; <a href="/entry/606974">606974</a>). <a href="#9" class="mim-tip-reference" title="Ungar, D., Oka, T., Brittle, E. E., Vasile, E., Lupashin, V. V., Chatterton, J. E., Heuser, J. E., Krieger, M., Waters, M. G. <strong>Characterization of a mammalian Golgi-localized protein complex, COG, that is required for normal Golgi morphology and function.</strong> J. Cell Biol. 157: 405-415, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11980916/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11980916</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11980916[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/10.1083/jcb.200202016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11980916">Ungar et al. (2002)</a> concluded that the COG complex is critical for the structure and function of the Golgi apparatus and can influence intracellular membrane trafficking. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11980916" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#7" class="mim-tip-reference" title="Richardson, B. C., Smith, R. D., Ungar, D., Nakamura, A., Jeffrey, P. D., Lupashin, V. V., Hughson, F. M. <strong>Structural basis for a human glycosylation disorder caused by mutation of the COG4 gene.</strong> Proc. Nat. Acad. Sci. 106: 13329-13334, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19651599/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19651599</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19651599[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/10.1073/pnas.0901966106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19651599">Richardson et al. (2009)</a> determined the crystal structure of the C-terminal 250 residues of human COG4. The Arg729 residue (see <a href="#0001">606976.0001</a>) resides at the center of a salt bridge network that stabilizes a small C-terminal domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19651599" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#6" class="mim-tip-reference" title="Reynders, E., Foulquier, F., Teles, E. L., Quelhas, D., Morelle, W., Rabouille, C., Annaert, W., Matthijs, G. <strong>Golgi function and dysfunction in the first COG4-deficient CDG type II patient.</strong> Hum. Molec. Genet. 18: 3244-3256, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19494034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19494034</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19494034[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/ddp262" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19494034">Reynders et al. (2009)</a> noted that the COG4 gene maps to chromosome 16q22.1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19494034" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using coimmunoprecipitation analysis and pull-down assays in human cells, <a href="#3" class="mim-tip-reference" title="Laufman, O., Kedan, A., Hong, W., Lev, S. <strong>Direct interaction between the COG complex and the SM protein, Sly1, is required for Golgi SNARE pairing.</strong> EMBO J. 28: 2006-20017, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19536132/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19536132</a>] [<a href="https://doi.org/10.1038/emboj.2009.168" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19536132">Laufman et al. (2009)</a> found that SLY1 (SCFD1; <a href="/entry/618207">618207</a>) interacted with the COG complex via the COG4 subunit. Mutation analysis revealed that amino acids 1 to 84 of COG4 contained a SLY1-binding site, with residues glu53 and glu71 playing a crucial role in SLY1 binding. The authors noted that this region of COG4 is highly conserved throughout evolution, with the exception of the S. cerevisiae ortholog. Further analysis showed that the COG4-SLY1 interaction was required for colocalization of SNARE complex proteins and for assembly of the complex. Disruption of the COG4-SLY1 interaction impaired pairing of SNAREs involved in intra-Golgi transport and thereby attenuated Golgi-to-ER retrograde transport. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19536132" 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 href="#6" class="mim-tip-reference" title="Reynders, E., Foulquier, F., Teles, E. L., Quelhas, D., Morelle, W., Rabouille, C., Annaert, W., Matthijs, G. <strong>Golgi function and dysfunction in the first COG4-deficient CDG type II patient.</strong> Hum. Molec. Genet. 18: 3244-3256, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19494034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19494034</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19494034[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/ddp262" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19494034">Reynders et al. (2009)</a> reported a Portuguese patient with congenital disorder of glycosylation type IIj (CDG2J; <a href="/entry/613489">613489</a>) and identified compound heterozygosity for a missense mutation in the COG4 gene (<a href="#0001">606976.0001</a>) and a large deletion encompassing most of the COG4 gene and part of the FUK gene (<a href="/entry/608675">608675</a>) (<a href="#0002">606976.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19494034" 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 an Indian child with a severe form of CDG2J, originally reported by <a href="#4" class="mim-tip-reference" title="Miura, Y., Tay, S. K. H., Aw, M. M., Eklund, E. A., Freeze, H. H. <strong>Clinical and biochemical characterization of a patient with congenital disorder of glycosylation (CDG) IIX.</strong> J. Pediat. 147: 851-853, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16356446/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16356446</a>] [<a href="https://doi.org/10.1016/j.jpeds.2005.07.038" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16356446">Miura et al. (2005)</a>, <a href="#5" class="mim-tip-reference" title="Ng, B. G., Sharma, V., Sun, L., Loh, E., Hong, W., Tay, S. K. H., Freeze, H. H. <strong>Identification of the first COG-CDG patient of Indian origin.</strong> Molec. Genet. Metab. 102: 364-367, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21185756/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21185756</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21185756[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ymgme.2010.11.161" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21185756">Ng et al. (2011)</a> identified compound heterozygosity for 2 mutations in the COG4 gene (<a href="#0003">606976.0003</a>-<a href="#0004">606976.0004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16356446+21185756" 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><strong><em>Saul-Wilson Syndrome</em></strong></p><p>
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In 14 patients with Saul-Wilson syndrome (SWILS; <a href="/entry/618150">618150</a>), including patient 2 in the report of <a href="#8" class="mim-tip-reference" title="Saul, R. A., Wilson, W. G. <strong>A 'new' skeletal dysplasia in two unrelated boys.</strong> Am. J. Med. Genet. 35: 388-393, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2309787/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2309787</a>] [<a href="https://doi.org/10.1002/ajmg.1320350315" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2309787">Saul and Wilson (1990)</a> and patient 1 in the report of <a href="#2" class="mim-tip-reference" title="Hersh, J. H., Joyce, M. R., Spranger, J., Goatley, E. C., Lachman, R. S., Bhatt, S., Rimoin, D. L. <strong>Microcephalic osteodysplastic dysplasia.</strong> Am. J. Med. Genet. 51: 194-199, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8074143/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8074143</a>] [<a href="https://doi.org/10.1002/ajmg.1320510304" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8074143">Hersh et al. (1994)</a>, <a href="#1" class="mim-tip-reference" title="Ferreira, C. R., Xia, Z.-J., Clement, A., Parry, D. A., Davids, M., Taylan, F., Sharma, P., Turgeon, C. T., Blanco-Sanchez, B., Ng, B. G., Logan, C. V., Wolfe, L. A., and 44 others. <strong>A recurrent de novo heterozygous COG4 substitution leads to Saul-Wilson syndrome, disrupted vesicular trafficking, and altered proteoglycan glycosylation.</strong> Am. J. Hum. Genet. 103: 553-567, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30290151/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30290151</a>] [<a href="https://doi.org/10.1016/j.ajhg.2018.09.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30290151">Ferreira et al. (2018)</a> identified 2 different de novo heterozygous mutations in the COG4 gene, c.1546G-A (<a href="#0005">606976.0005</a>) and c.1546G-C (<a href="#0006">606976.0006</a>), both of which give rise to an identical missense mutation (G516R). The mutations, which were found by whole-exome or whole-genome sequencing, were confirmed by Sanger sequencing. <a href="#1" class="mim-tip-reference" title="Ferreira, C. R., Xia, Z.-J., Clement, A., Parry, D. A., Davids, M., Taylan, F., Sharma, P., Turgeon, C. T., Blanco-Sanchez, B., Ng, B. G., Logan, C. V., Wolfe, L. A., and 44 others. <strong>A recurrent de novo heterozygous COG4 substitution leads to Saul-Wilson syndrome, disrupted vesicular trafficking, and altered proteoglycan glycosylation.</strong> Am. J. Hum. Genet. 103: 553-567, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30290151/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30290151</a>] [<a href="https://doi.org/10.1016/j.ajhg.2018.09.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30290151">Ferreira et al. (2018)</a> found that the subcellular localization of COG subunits was not altered in the patients. Patient fibroblasts exhibited delayed anterograde vesicular trafficking from the endoplamic reticulum (ER) to the Golgi and accelerated retrograde vesicular recycling from the Golgi to the ER. This altered steady-state equilibrium led to a decrease in Golgi volume, as well as morphologic abnormalities with collapse of the Golgi stacks. Despite these abnormalities of the Golgi apparatus, protein glycosylation in patient sera and fibroblasts was not notably altered, but decorin (<a href="/entry/125255">125255</a>), a proteoglycan secreted into the extracellular matrix, showed altered Golgi-dependent glycosylation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=30290151+8074143+2309787" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=606976[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<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> rs267606740 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606740;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/rs267606740?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=rs267606740" 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=rs267606740" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p><a href="#6" class="mim-tip-reference" title="Reynders, E., Foulquier, F., Teles, E. L., Quelhas, D., Morelle, W., Rabouille, C., Annaert, W., Matthijs, G. <strong>Golgi function and dysfunction in the first COG4-deficient CDG type II patient.</strong> Hum. Molec. Genet. 18: 3244-3256, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19494034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19494034</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19494034[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/ddp262" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19494034">Reynders et al. (2009)</a> reported a Portuguese boy with congenital disorder of glycosylation type IIj (CDG2J; <a href="/entry/613489">613489</a>) and identified compound heterozygosity for a 2185C-T transition in exon 18 of the COG4 gene, resulting in an arg729-to-trp (R729W) substitution at a conserved residue, and a large deletion (<a href="#0002">606976.0002</a>) of approximately 400 kb with the distal breakpoint between intron 2 and exon 5 of the COG4 gene and the proximal breakpoint upstream of the FUK gene (<a href="/entry/608675">608675</a>). The FUK gene encodes L-fucose kinase, which is necessary for the reutilization of fucose after the degradation of oligosaccharides. Because no decreased fucosylation was observed in the N-glycans of the patient, the authors concluded that the 'partial monosomy' of this gene was not pathogenic. The R729W mutation was not identified in over 100 European control alleles. Western blot analysis of patient fibroblasts showed reduced COG4 protein levels compared to control, and downregulation of COG4 expression additionally affected expression or stability of other lobe A subunits. Despite this, full complex formation was maintained albeit to a lower extent. Subunits were present in a cytosolic pool and full complex formation assisted tethering preceding membrane fusion. The unrelated father and mother were heterozygous for the R729W mutation or the deletion, respectively, and Western blot analysis of parental fibroblasts showed normal COG4 protein levels. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19494034" 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 determining the crystal structure of a COG4 C-terminal fragment, <a href="#7" class="mim-tip-reference" title="Richardson, B. C., Smith, R. D., Ungar, D., Nakamura, A., Jeffrey, P. D., Lupashin, V. V., Hughson, F. M. <strong>Structural basis for a human glycosylation disorder caused by mutation of the COG4 gene.</strong> Proc. Nat. Acad. Sci. 106: 13329-13334, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19651599/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19651599</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19651599[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/10.1073/pnas.0901966106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19651599">Richardson et al. (2009)</a> determined that the R729 residue occupies a key position at the center of a salt bridge network, thereby stabilizing the small C-terminal domain. Knockdown of COG4 in HeLa cells by use of a COG4-specific shRNA plasmid resulted in disruption of glycosylation of cell surface proteins. A full-length COG4 containing the R729W mutation failed to rescue the glycosylation defect in these knockdown cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19651599" 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>For discussion of the large deletion with the distal breakpoint between intron 2 and exon 5 of the COG4 gene and the proximal breakpoint upstream of the FUK gene (<a href="/entry/608675">608675</a>) that was found in compound heterozygous state in a patient with congenital disorder of glycosylation type IIj (CDG2J; <a href="/entry/613489">613489</a>) by <a href="#6" class="mim-tip-reference" title="Reynders, E., Foulquier, F., Teles, E. L., Quelhas, D., Morelle, W., Rabouille, C., Annaert, W., Matthijs, G. <strong>Golgi function and dysfunction in the first COG4-deficient CDG type II patient.</strong> Hum. Molec. Genet. 18: 3244-3256, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19494034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19494034</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19494034[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/ddp262" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19494034">Reynders et al. (2009)</a>, see <a href="#0001">606976.0001</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19494034" 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">rs387907202 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387907202;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=rs387907202" 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=rs387907202" 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=RCV000024608" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000024608" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000024608</a>
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<p>In an Indian child with congenital disorder of glycosylation type IIj (CDG2J; <a href="/entry/613489">613489</a>), <a href="#5" class="mim-tip-reference" title="Ng, B. G., Sharma, V., Sun, L., Loh, E., Hong, W., Tay, S. K. H., Freeze, H. H. <strong>Identification of the first COG-CDG patient of Indian origin.</strong> Molec. Genet. Metab. 102: 364-367, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21185756/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21185756</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21185756[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ymgme.2010.11.161" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21185756">Ng et al. (2011)</a> identified compound heterozygosity for 2 mutations in the COG4 gene: a 697G-T transversion in exon 5 resulting in a glu233-to-ter (E233X) substitution, and a 2318T-G transversion in exon 19 resulting in a leu773-to-arg (L773R; <a href="#0004">606976.0004</a>) substitution. The L773R mutation was inherited from the unaffected mother, but the E233X mutation was not found in either parent, consistent with a de novo occurrence. Most of the E233X unstable transcript was subject to nonsense-mediated mRNA decay. The patient had profound developmental delay, hypotonia, failure to thrive, seizures, coagulopathy, liver cirrhosis, and recurrent infections that were ultimately fatal around age 2 years. The patient had 2 unaffected sibs. Patient serum N-glycans showed deficiencies in both sialylation and galactosylation, and patient fibroblasts showed impaired O-glycosylation, indicating a combined deficiency. Patient fibroblasts also showed a defect in Brefeldin A (BFA)-induced retrograde transport of Golgi proteins back to the endoplasmic reticulum. There was an isolated reduction in COG4 protein expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21185756" 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> rs387907203 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387907203;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/rs387907203?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=rs387907203" 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=rs387907203" 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=RCV000024609" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000024609" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000024609</a>
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<p>For discussion of the leu773-to-arg (L773R) mutation in the COG4 gene that was found in compound heterozygous state in a patient with congenital disorder of glycosylation type IIj (CDG2J; <a href="/entry/613489">613489</a>) by <a href="#5" class="mim-tip-reference" title="Ng, B. G., Sharma, V., Sun, L., Loh, E., Hong, W., Tay, S. K. H., Freeze, H. H. <strong>Identification of the first COG-CDG patient of Indian origin.</strong> Molec. Genet. Metab. 102: 364-367, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21185756/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21185756</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21185756[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ymgme.2010.11.161" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21185756">Ng et al. (2011)</a>, see <a href="#0003">606976.0003</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21185756" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 SAUL-WILSON SYNDROME</strong>
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COG4, GLY516ARG, 1546G-A
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1555575860 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1555575860;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=rs1555575860" 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=rs1555575860" 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=RCV000522988 OR RCV000625979 OR RCV000710020 OR RCV001266583" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000522988, RCV000625979, RCV000710020, RCV001266583" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000522988...</a>
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<p>In 11 patients with Saul-Wilson syndrome (SWILS; <a href="/entry/618150">618150</a>), including patient 1 in the report of <a href="#2" class="mim-tip-reference" title="Hersh, J. H., Joyce, M. R., Spranger, J., Goatley, E. C., Lachman, R. S., Bhatt, S., Rimoin, D. L. <strong>Microcephalic osteodysplastic dysplasia.</strong> Am. J. Med. Genet. 51: 194-199, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8074143/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8074143</a>] [<a href="https://doi.org/10.1002/ajmg.1320510304" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8074143">Hersh et al. (1994)</a>, <a href="#1" class="mim-tip-reference" title="Ferreira, C. R., Xia, Z.-J., Clement, A., Parry, D. A., Davids, M., Taylan, F., Sharma, P., Turgeon, C. T., Blanco-Sanchez, B., Ng, B. G., Logan, C. V., Wolfe, L. A., and 44 others. <strong>A recurrent de novo heterozygous COG4 substitution leads to Saul-Wilson syndrome, disrupted vesicular trafficking, and altered proteoglycan glycosylation.</strong> Am. J. Hum. Genet. 103: 553-567, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30290151/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30290151</a>] [<a href="https://doi.org/10.1016/j.ajhg.2018.09.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30290151">Ferreira et al. (2018)</a> identified a de novo heterozygous c.1546G-A transition (c.1546G-A, NM_015386.2) in the COG4 gene, resulting in a gly516-to-arg (G516R) substitution. The mutations, which were found by whole-exome or whole-genome sequencing, were confirmed by Sanger sequencing. Compared to control cell lines, fibroblasts from affected individuals showed normal mRNA expression and protein level of COG4 and other COG subunits, confirming that the variant leads to production of a stable protein. Protein modeling predicted the loss of a loop structure in the mutant protein; however, binding of COG4 to other COG subunits was not altered. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=30290151+8074143" 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>.0006 SAUL-WILSON SYNDROME</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1555575860 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1555575860;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=rs1555575860" 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=rs1555575860" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000710021" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000710021" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000710021</a>
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<span class="mim-text-font">
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<p>In 3 patients with Saul-Wilson syndrome (SWILS; <a href="/entry/618150">618150</a>), including patient 2 in the report of <a href="#8" class="mim-tip-reference" title="Saul, R. A., Wilson, W. G. <strong>A 'new' skeletal dysplasia in two unrelated boys.</strong> Am. J. Med. Genet. 35: 388-393, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2309787/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2309787</a>] [<a href="https://doi.org/10.1002/ajmg.1320350315" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2309787">Saul and Wilson (1990)</a>, <a href="#1" class="mim-tip-reference" title="Ferreira, C. R., Xia, Z.-J., Clement, A., Parry, D. A., Davids, M., Taylan, F., Sharma, P., Turgeon, C. T., Blanco-Sanchez, B., Ng, B. G., Logan, C. V., Wolfe, L. A., and 44 others. <strong>A recurrent de novo heterozygous COG4 substitution leads to Saul-Wilson syndrome, disrupted vesicular trafficking, and altered proteoglycan glycosylation.</strong> Am. J. Hum. Genet. 103: 553-567, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30290151/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30290151</a>] [<a href="https://doi.org/10.1016/j.ajhg.2018.09.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30290151">Ferreira et al. (2018)</a> identified a de novo heterozygous c.1546G-C transversion (c.1546G-C, NM_015386.2) in the COG4 gene, resulting in a gly516-to-arg (G516R) substitution. The mutations, which were found by whole-exome or whole-genome sequencing, were confirmed by Sanger sequencing. Compared to control cell lines, fibroblasts from affected individuals showed normal mRNA expression and protein level of COG4 and other COG subunits, confirming that the variant leads to production of a stable protein. Protein modeling predicted the loss of a loop structure in the mutant protein; however, binding of COG4 to other COG subunits was not altered. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=30290151+2309787" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span class="mim-font">
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<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>REFERENCES</strong>
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<a id="Ferreira2018" class="mim-anchor"></a>
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Ferreira, C. R., Xia, Z.-J., Clement, A., Parry, D. A., Davids, M., Taylan, F., Sharma, P., Turgeon, C. T., Blanco-Sanchez, B., Ng, B. G., Logan, C. V., Wolfe, L. A., and 44 others.
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<strong>A recurrent de novo heterozygous COG4 substitution leads to Saul-Wilson syndrome, disrupted vesicular trafficking, and altered proteoglycan glycosylation.</strong>
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Am. J. Hum. Genet. 103: 553-567, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30290151/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30290151</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30290151" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ajhg.2018.09.003" target="_blank">Full Text</a>]
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<a id="Hersh1994" class="mim-anchor"></a>
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Hersh, J. H., Joyce, M. R., Spranger, J., Goatley, E. C., Lachman, R. S., Bhatt, S., Rimoin, D. L.
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<strong>Microcephalic osteodysplastic dysplasia.</strong>
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Am. J. Med. Genet. 51: 194-199, 1994.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8074143/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8074143</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8074143" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.1320510304" target="_blank">Full Text</a>]
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<a id="Laufman2009" class="mim-anchor"></a>
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Laufman, O., Kedan, A., Hong, W., Lev, S.
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<strong>Direct interaction between the COG complex and the SM protein, Sly1, is required for Golgi SNARE pairing.</strong>
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EMBO J. 28: 2006-20017, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19536132/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19536132</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19536132" 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/emboj.2009.168" target="_blank">Full Text</a>]
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Miura, Y., Tay, S. K. H., Aw, M. M., Eklund, E. A., Freeze, H. H.
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<strong>Clinical and biochemical characterization of a patient with congenital disorder of glycosylation (CDG) IIX.</strong>
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J. Pediat. 147: 851-853, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16356446/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16356446</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16356446" 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.jpeds.2005.07.038" target="_blank">Full Text</a>]
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Ng, B. G., Sharma, V., Sun, L., Loh, E., Hong, W., Tay, S. K. H., Freeze, H. H.
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<strong>Identification of the first COG-CDG patient of Indian origin.</strong>
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Molec. Genet. Metab. 102: 364-367, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21185756/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21185756</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21185756[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=21185756" 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.ymgme.2010.11.161" target="_blank">Full Text</a>]
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<a id="Reynders2009" class="mim-anchor"></a>
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Reynders, E., Foulquier, F., Teles, E. L., Quelhas, D., Morelle, W., Rabouille, C., Annaert, W., Matthijs, G.
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<strong>Golgi function and dysfunction in the first COG4-deficient CDG type II patient.</strong>
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Hum. Molec. Genet. 18: 3244-3256, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19494034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19494034</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19494034[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=19494034" 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/ddp262" target="_blank">Full Text</a>]
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<a id="Richardson2009" class="mim-anchor"></a>
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Richardson, B. C., Smith, R. D., Ungar, D., Nakamura, A., Jeffrey, P. D., Lupashin, V. V., Hughson, F. M.
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<strong>Structural basis for a human glycosylation disorder caused by mutation of the COG4 gene.</strong>
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Proc. Nat. Acad. Sci. 106: 13329-13334, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19651599/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19651599</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19651599[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=19651599" 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/10.1073/pnas.0901966106" 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="Saul1990" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Saul, R. A., Wilson, W. G.
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<strong>A 'new' skeletal dysplasia in two unrelated boys.</strong>
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Am. J. Med. Genet. 35: 388-393, 1990.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2309787/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2309787</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2309787" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.1320350315" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="9" class="mim-anchor"></a>
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<a id="Ungar2002" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Ungar, D., Oka, T., Brittle, E. E., Vasile, E., Lupashin, V. V., Chatterton, J. E., Heuser, J. E., Krieger, M., Waters, M. G.
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<strong>Characterization of a mammalian Golgi-localized protein complex, COG, that is required for normal Golgi morphology and function.</strong>
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J. Cell Biol. 157: 405-415, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11980916/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11980916</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11980916[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=11980916" 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/10.1083/jcb.200202016" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="10" class="mim-anchor"></a>
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<a id="Whyte2001" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Whyte, J. R. C., Munro, S.
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<strong>The Sec34/35 Golgi transport complex is related to the exocyst, defining a family of complexes involved in multiple steps of membrane traffic.</strong>
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Dev. Cell 1: 527-537, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11703943/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11703943</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11703943" 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/s1534-5807(01)00063-6" target="_blank">Full Text</a>]
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</p>
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</div>
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</ol>
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<br />
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div 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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Bao Lige - updated : 11/29/2018
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</span>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh - updated : 10/15/2018<br>Ada Hamosh - updated : 10/15/2018<br>Joanna S. Amberger - updated : 06/29/2015<br>Cassandra L. Kniffin - updated : 6/19/2012<br>George E. Tiller - updated : 7/7/2010
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</span>
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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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Paul J. Converse : 5/23/2002
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</span>
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</div>
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<a id="editHistory" class="mim-anchor"></a>
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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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mgross : 11/29/2018
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</span>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 10/15/2018<br>carol : 06/29/2015<br>mcolton : 6/16/2015<br>carol : 6/21/2012<br>ckniffin : 6/19/2012<br>wwang : 7/20/2010<br>wwang : 7/20/2010<br>terry : 7/7/2010<br>mgross : 5/23/2002
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</span>
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</div>
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<div class="container visible-print-block">
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 606976
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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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COMPONENT OF OLIGOMERIC GOLGI COMPLEX 4; COG4
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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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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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COD1, S. CEREVISIAE, HOMOLOG OF; COD1
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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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<strong><em>HGNC Approved Gene Symbol: COG4</em></strong>
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</span>
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</p>
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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> 718751000;
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</span>
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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: 16q22.1
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Genomic coordinates <span class="small">(GRCh38)</span> : 16:70,480,567-70,523,554 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="2">
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<span class="mim-font">
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16q22.1
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</span>
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</td>
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<td>
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<span class="mim-font">
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Congenital disorder of glycosylation, type IIj
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</span>
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</td>
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<td>
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<span class="mim-font">
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|
613489
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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<tr>
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<td>
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<span class="mim-font">
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Saul-Wilson syndrome
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</span>
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</td>
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<td>
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<span class="mim-font">
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618150
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</td>
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</tbody>
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</table>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Multiprotein complexes are key determinants of Golgi apparatus structure and its capacity for intracellular transport and glycoprotein modification. Several complexes have been identified, including the Golgi transport complex (GTC), the LDLC complex, which is involved in glycosylation reactions, and the SEC34 complex, which is involved in vesicular transport. These 3 complexes are identical and have been termed the conserved oligomeric Golgi (COG) complex, which includes COG4 (Ungar et al., 2002). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By database searching for sequences homologous to the yeast complexed with Dor1 (COG8; 606979) (COD) proteins, Whyte and Munro (2001) identified cDNAs encoding COG4, which they called COD1, and other members of the COG complex. The deduced 785-amino acid COG4 protein contains an N-terminal coiled-coil region. Coiled-coil regions are found in all members of the COG complex and may be involved in holding the complex together or in binding other proteins involved in vesicle docking and fusion. </p><p>By SDS-PAGE analysis of bovine brain cytosol, Ungar et al. (2002) identified the 8 subunits of the COG complex. Immunofluorescence microscopy demonstrated that COG1 (LDLB; 606973) colocalizes with COG7 (606978), as well as with COG3 (606975) and COG5 (606821), with a Golgi marker in a perinuclear distribution. Immunoprecipitation analysis showed that all COG subunits interact with COG2 (LDLC; 606974). Ungar et al. (2002) concluded that the COG complex is critical for the structure and function of the Golgi apparatus and can influence intracellular membrane trafficking. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Biochemical Features</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Richardson et al. (2009) determined the crystal structure of the C-terminal 250 residues of human COG4. The Arg729 residue (see 606976.0001) resides at the center of a salt bridge network that stabilizes a small C-terminal domain. </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>Reynders et al. (2009) noted that the COG4 gene maps to chromosome 16q22.1. </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>Using coimmunoprecipitation analysis and pull-down assays in human cells, Laufman et al. (2009) found that SLY1 (SCFD1; 618207) interacted with the COG complex via the COG4 subunit. Mutation analysis revealed that amino acids 1 to 84 of COG4 contained a SLY1-binding site, with residues glu53 and glu71 playing a crucial role in SLY1 binding. The authors noted that this region of COG4 is highly conserved throughout evolution, with the exception of the S. cerevisiae ortholog. Further analysis showed that the COG4-SLY1 interaction was required for colocalization of SNARE complex proteins and for assembly of the complex. Disruption of the COG4-SLY1 interaction impaired pairing of SNAREs involved in intra-Golgi transport and thereby attenuated Golgi-to-ER retrograde transport. </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><strong><em>Congenital Disorder of Glycosylation, Type IIj</em></strong></p><p>
|
|
Reynders et al. (2009) reported a Portuguese patient with congenital disorder of glycosylation type IIj (CDG2J; 613489) and identified compound heterozygosity for a missense mutation in the COG4 gene (606976.0001) and a large deletion encompassing most of the COG4 gene and part of the FUK gene (608675) (606976.0002). </p><p>In an Indian child with a severe form of CDG2J, originally reported by Miura et al. (2005), Ng et al. (2011) identified compound heterozygosity for 2 mutations in the COG4 gene (606976.0003-606976.0004). </p><p><strong><em>Saul-Wilson Syndrome</em></strong></p><p>
|
|
In 14 patients with Saul-Wilson syndrome (SWILS; 618150), including patient 2 in the report of Saul and Wilson (1990) and patient 1 in the report of Hersh et al. (1994), Ferreira et al. (2018) identified 2 different de novo heterozygous mutations in the COG4 gene, c.1546G-A (606976.0005) and c.1546G-C (606976.0006), both of which give rise to an identical missense mutation (G516R). The mutations, which were found by whole-exome or whole-genome sequencing, were confirmed by Sanger sequencing. Ferreira et al. (2018) found that the subcellular localization of COG subunits was not altered in the patients. Patient fibroblasts exhibited delayed anterograde vesicular trafficking from the endoplamic reticulum (ER) to the Golgi and accelerated retrograde vesicular recycling from the Golgi to the ER. This altered steady-state equilibrium led to a decrease in Golgi volume, as well as morphologic abnormalities with collapse of the Golgi stacks. Despite these abnormalities of the Golgi apparatus, protein glycosylation in patient sera and fibroblasts was not notably altered, but decorin (125255), a proteoglycan secreted into the extracellular matrix, showed altered Golgi-dependent glycosylation. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>6 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IIj</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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COG4, ARG729TRP
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<br />
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SNP: rs267606740,
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gnomAD: rs267606740,
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ClinVar: RCV000003837, RCV001703413, RCV002251866
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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>Reynders et al. (2009) reported a Portuguese boy with congenital disorder of glycosylation type IIj (CDG2J; 613489) and identified compound heterozygosity for a 2185C-T transition in exon 18 of the COG4 gene, resulting in an arg729-to-trp (R729W) substitution at a conserved residue, and a large deletion (606976.0002) of approximately 400 kb with the distal breakpoint between intron 2 and exon 5 of the COG4 gene and the proximal breakpoint upstream of the FUK gene (608675). The FUK gene encodes L-fucose kinase, which is necessary for the reutilization of fucose after the degradation of oligosaccharides. Because no decreased fucosylation was observed in the N-glycans of the patient, the authors concluded that the 'partial monosomy' of this gene was not pathogenic. The R729W mutation was not identified in over 100 European control alleles. Western blot analysis of patient fibroblasts showed reduced COG4 protein levels compared to control, and downregulation of COG4 expression additionally affected expression or stability of other lobe A subunits. Despite this, full complex formation was maintained albeit to a lower extent. Subunits were present in a cytosolic pool and full complex formation assisted tethering preceding membrane fusion. The unrelated father and mother were heterozygous for the R729W mutation or the deletion, respectively, and Western blot analysis of parental fibroblasts showed normal COG4 protein levels. </p><p>By determining the crystal structure of a COG4 C-terminal fragment, Richardson et al. (2009) determined that the R729 residue occupies a key position at the center of a salt bridge network, thereby stabilizing the small C-terminal domain. Knockdown of COG4 in HeLa cells by use of a COG4-specific shRNA plasmid resulted in disruption of glycosylation of cell surface proteins. A full-length COG4 containing the R729W mutation failed to rescue the glycosylation defect in these knockdown cells. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IIj</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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COG4, 400-KB DEL
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<br />
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ClinVar: RCV000003838
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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>For discussion of the large deletion with the distal breakpoint between intron 2 and exon 5 of the COG4 gene and the proximal breakpoint upstream of the FUK gene (608675) that was found in compound heterozygous state in a patient with congenital disorder of glycosylation type IIj (CDG2J; 613489) by Reynders et al. (2009), see 606976.0001. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IIj</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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COG4, GLU233TER
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<br />
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SNP: rs387907202,
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ClinVar: RCV000024608
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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 an Indian child with congenital disorder of glycosylation type IIj (CDG2J; 613489), Ng et al. (2011) identified compound heterozygosity for 2 mutations in the COG4 gene: a 697G-T transversion in exon 5 resulting in a glu233-to-ter (E233X) substitution, and a 2318T-G transversion in exon 19 resulting in a leu773-to-arg (L773R; 606976.0004) substitution. The L773R mutation was inherited from the unaffected mother, but the E233X mutation was not found in either parent, consistent with a de novo occurrence. Most of the E233X unstable transcript was subject to nonsense-mediated mRNA decay. The patient had profound developmental delay, hypotonia, failure to thrive, seizures, coagulopathy, liver cirrhosis, and recurrent infections that were ultimately fatal around age 2 years. The patient had 2 unaffected sibs. Patient serum N-glycans showed deficiencies in both sialylation and galactosylation, and patient fibroblasts showed impaired O-glycosylation, indicating a combined deficiency. Patient fibroblasts also showed a defect in Brefeldin A (BFA)-induced retrograde transport of Golgi proteins back to the endoplasmic reticulum. There was an isolated reduction in COG4 protein expression. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IIj</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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COG4, LEU773ARG
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<br />
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SNP: rs387907203,
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gnomAD: rs387907203,
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ClinVar: RCV000024609
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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>For discussion of the leu773-to-arg (L773R) mutation in the COG4 gene that was found in compound heterozygous state in a patient with congenital disorder of glycosylation type IIj (CDG2J; 613489) by Ng et al. (2011), see 606976.0003. </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>.0005 SAUL-WILSON 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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COG4, GLY516ARG, 1546G-A
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<br />
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SNP: rs1555575860,
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ClinVar: RCV000522988, RCV000625979, RCV000710020, RCV001266583
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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 11 patients with Saul-Wilson syndrome (SWILS; 618150), including patient 1 in the report of Hersh et al. (1994), Ferreira et al. (2018) identified a de novo heterozygous c.1546G-A transition (c.1546G-A, NM_015386.2) in the COG4 gene, resulting in a gly516-to-arg (G516R) substitution. The mutations, which were found by whole-exome or whole-genome sequencing, were confirmed by Sanger sequencing. Compared to control cell lines, fibroblasts from affected individuals showed normal mRNA expression and protein level of COG4 and other COG subunits, confirming that the variant leads to production of a stable protein. Protein modeling predicted the loss of a loop structure in the mutant protein; however, binding of COG4 to other COG subunits was not altered. </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>.0006 SAUL-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
COG4, GLY516ARG, 1546G-C
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|
|
<br />
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|
|
SNP: rs1555575860,
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|
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|
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|
|
ClinVar: RCV000710021
|
|
|
|
|
|
</span>
|
|
</div>
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 patients with Saul-Wilson syndrome (SWILS; 618150), including patient 2 in the report of Saul and Wilson (1990), Ferreira et al. (2018) identified a de novo heterozygous c.1546G-C transversion (c.1546G-C, NM_015386.2) in the COG4 gene, resulting in a gly516-to-arg (G516R) substitution. The mutations, which were found by whole-exome or whole-genome sequencing, were confirmed by Sanger sequencing. Compared to control cell lines, fibroblasts from affected individuals showed normal mRNA expression and protein level of COG4 and other COG subunits, confirming that the variant leads to production of a stable protein. Protein modeling predicted the loss of a loop structure in the mutant protein; however, binding of COG4 to other COG subunits was not altered. </p>
|
|
</span>
|
|
</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>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
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<p />
|
|
</div>
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<div>
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<ol>
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<li>
|
|
<p class="mim-text-font">
|
|
Ferreira, C. R., Xia, Z.-J., Clement, A., Parry, D. A., Davids, M., Taylan, F., Sharma, P., Turgeon, C. T., Blanco-Sanchez, B., Ng, B. G., Logan, C. V., Wolfe, L. A., and 44 others.
|
|
<strong>A recurrent de novo heterozygous COG4 substitution leads to Saul-Wilson syndrome, disrupted vesicular trafficking, and altered proteoglycan glycosylation.</strong>
|
|
Am. J. Hum. Genet. 103: 553-567, 2018.
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[PubMed: 30290151]
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[Full Text: https://doi.org/10.1016/j.ajhg.2018.09.003]
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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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Hersh, J. H., Joyce, M. R., Spranger, J., Goatley, E. C., Lachman, R. S., Bhatt, S., Rimoin, D. L.
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<strong>Microcephalic osteodysplastic dysplasia.</strong>
|
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Am. J. Med. Genet. 51: 194-199, 1994.
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[PubMed: 8074143]
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[Full Text: https://doi.org/10.1002/ajmg.1320510304]
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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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Laufman, O., Kedan, A., Hong, W., Lev, S.
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<strong>Direct interaction between the COG complex and the SM protein, Sly1, is required for Golgi SNARE pairing.</strong>
|
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EMBO J. 28: 2006-20017, 2009.
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[PubMed: 19536132]
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[Full Text: https://doi.org/10.1038/emboj.2009.168]
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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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Miura, Y., Tay, S. K. H., Aw, M. M., Eklund, E. A., Freeze, H. H.
|
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<strong>Clinical and biochemical characterization of a patient with congenital disorder of glycosylation (CDG) IIX.</strong>
|
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J. Pediat. 147: 851-853, 2005.
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[PubMed: 16356446]
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[Full Text: https://doi.org/10.1016/j.jpeds.2005.07.038]
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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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Ng, B. G., Sharma, V., Sun, L., Loh, E., Hong, W., Tay, S. K. H., Freeze, H. H.
|
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<strong>Identification of the first COG-CDG patient of Indian origin.</strong>
|
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Molec. Genet. Metab. 102: 364-367, 2011.
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[PubMed: 21185756]
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[Full Text: https://doi.org/10.1016/j.ymgme.2010.11.161]
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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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Reynders, E., Foulquier, F., Teles, E. L., Quelhas, D., Morelle, W., Rabouille, C., Annaert, W., Matthijs, G.
|
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<strong>Golgi function and dysfunction in the first COG4-deficient CDG type II patient.</strong>
|
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Hum. Molec. Genet. 18: 3244-3256, 2009.
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[PubMed: 19494034]
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[Full Text: https://doi.org/10.1093/hmg/ddp262]
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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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Richardson, B. C., Smith, R. D., Ungar, D., Nakamura, A., Jeffrey, P. D., Lupashin, V. V., Hughson, F. M.
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<strong>Structural basis for a human glycosylation disorder caused by mutation of the COG4 gene.</strong>
|
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Proc. Nat. Acad. Sci. 106: 13329-13334, 2009.
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[PubMed: 19651599]
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[Full Text: https://doi.org/10.1073/pnas.0901966106]
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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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Saul, R. A., Wilson, W. G.
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<strong>A 'new' skeletal dysplasia in two unrelated boys.</strong>
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Am. J. Med. Genet. 35: 388-393, 1990.
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[PubMed: 2309787]
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[Full Text: https://doi.org/10.1002/ajmg.1320350315]
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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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Ungar, D., Oka, T., Brittle, E. E., Vasile, E., Lupashin, V. V., Chatterton, J. E., Heuser, J. E., Krieger, M., Waters, M. G.
|
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<strong>Characterization of a mammalian Golgi-localized protein complex, COG, that is required for normal Golgi morphology and function.</strong>
|
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J. Cell Biol. 157: 405-415, 2002.
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[PubMed: 11980916]
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[Full Text: https://doi.org/10.1083/jcb.200202016]
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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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Whyte, J. R. C., Munro, S.
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<strong>The Sec34/35 Golgi transport complex is related to the exocyst, defining a family of complexes involved in multiple steps of membrane traffic.</strong>
|
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Dev. Cell 1: 527-537, 2001.
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[PubMed: 11703943]
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[Full Text: https://doi.org/10.1016/s1534-5807(01)00063-6]
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</p>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<div class="row">
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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<span class="text-nowrap mim-text-font">
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Contributors:
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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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Bao Lige - updated : 11/29/2018<br>Ada Hamosh - updated : 10/15/2018<br>Ada Hamosh - updated : 10/15/2018<br>Joanna S. Amberger - updated : 06/29/2015<br>Cassandra L. Kniffin - updated : 6/19/2012<br>George E. Tiller - updated : 7/7/2010
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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 class="row">
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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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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Paul J. Converse : 5/23/2002
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</span>
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</div>
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<div>
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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<span class="text-nowrap mim-text-font">
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Edit History:
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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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mgross : 11/29/2018<br>carol : 10/15/2018<br>carol : 06/29/2015<br>mcolton : 6/16/2015<br>carol : 6/21/2012<br>ckniffin : 6/19/2012<br>wwang : 7/20/2010<br>wwang : 7/20/2010<br>terry : 7/7/2010<br>mgross : 5/23/2002
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