3394 lines
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Entry
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- *609855 - COENZYME A SYNTHASE; COASY
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- OMIM
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<p>
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<span class="h4">*609855</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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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="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<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/609855">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>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000068120;t=ENST00000393818" 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=80347" 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=609855" 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 class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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<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=ENSG00000068120;t=ENST00000393818" 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_001042529,NM_001042532,NM_025233,XM_006722116,XM_011525300,XM_047436849,XM_047436850" 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_025233" 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=609855" 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=13080&isoform_id=13080_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/COASY" 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/894178,9502027,13623499,17981025,20465248,21594102,30583175,32363505,45501329,110227601,110227603,119581242,119581243,119581244,189054255,194383522,194386176,205277394,578831479,767996043,2217314118,2217314120,2462557983,2462557985,2462557987,2462557989" 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/Q13057" 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=80347" 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=ENSG00000068120;t=ENST00000393818" 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=COASY" 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=COASY" 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+80347" 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/COASY" 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:80347" 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/80347" 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=chr17&hgg_gene=ENST00000393818.3&hgg_start=42562148&hgg_end=42566277&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://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=609855[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 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=609855[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/COASY/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/ENSG00000068120" 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=COASY" 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=COASY" 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=COASY" 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=COASY&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/PA134867942" 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:29932" 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/FBgn0035632.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:1918993" 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/COASY#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:1918993" 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/80347/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=80347" 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=WBGene00022031;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-040912-137" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:80347" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=COASY&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> 732264002<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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609855
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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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COENZYME A SYNTHASE; COASY
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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>
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<span class="mim-font">
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PHOSPHOPANTETHEINE ADENYLYLTRANSFERASE/DEPHOSPHOCOENZYME A KINASE<br />
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PPAT/DPCK
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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">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=COASY" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">COASY</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/17/581?start=-3&limit=10&highlight=581">17q21.2</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr17:42562148-42566277&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'})">17:42,562,148-42,566,277</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</div>
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<div>
|
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
|
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</th>
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<th>
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Phenotype
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<span class="hidden-sm hidden-xs pull-right">
|
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<a href="/clinicalSynopsis/table?mimNumber=615643,618266" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
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</a>
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</span>
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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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<a href="/geneMap/17/581?start=-3&limit=10&highlight=581">
|
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17q21.2
|
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</a>
|
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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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Neurodegeneration with brain iron accumulation 6
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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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|
<a href="/entry/615643"> 615643 </a>
|
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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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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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<tr>
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<td>
|
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<span class="mim-font">
|
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Pontocerebellar hypoplasia, type 12
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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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|
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<a href="/entry/618266"> 618266 </a>
|
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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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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
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<p>Biosynthesis of coenzyme A (CoA) from pantothenic acid (vitamin B5) is an essential universal pathway in prokaryotes and eukaryotes. COASY is a bifunctional enzyme that catalyzes the 2 last steps in CoA synthesis. These activities are performed by 2 separate enzymes, phosphopantetheine adenylyltransferase (PPAT; <a href="https://enzyme.expasy.org/EC/2.7.7.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 2.7.7.3</a>) and dephospho-CoA kinase (DPCK; <a href="https://enzyme.expasy.org/EC/2.7.1.24" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 2.7.1.24</a>), in prokaryotes (<a href="#3" class="mim-tip-reference" title="Daugherty, M., Polanuyer, B., Farrell, M., Scholle, M., Lykidis, A., de Crecy-Lagard, V., Osterman, A. <strong>Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics.</strong> J. Biol. Chem. 277: 21431-21439, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11923312/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11923312</a>] [<a href="https://doi.org/10.1074/jbc.M201708200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11923312">Daugherty et al., 2002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11923312" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By searching for sequences similar to E. coli CoA biosynthesis enzymes, followed by PCR of a brain cDNA library, <a href="#3" class="mim-tip-reference" title="Daugherty, M., Polanuyer, B., Farrell, M., Scholle, M., Lykidis, A., de Crecy-Lagard, V., Osterman, A. <strong>Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics.</strong> J. Biol. Chem. 277: 21431-21439, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11923312/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11923312</a>] [<a href="https://doi.org/10.1074/jbc.M201708200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11923312">Daugherty et al. (2002)</a> cloned COASY, which they called PPAT/DPCK. The deduced 565-amino acid protein has an N-terminal domain, a central PPAT domain, and a C-terminal DPCK domain. The PPAT domain contains the conserved HxxH motif characteristic of nucleotidyltransferases. Northern blot analysis detected 2.2- and 2.6-kb COASY transcripts in most tissues and tumor cell lines examined. Expression was highest in kidney and liver and lowest in peripheral blood leukocytes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11923312" 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 searching for sequences similar to pig Coasy, followed by RT-PCR of a hepatoma cell line cDNA library, <a href="#1" class="mim-tip-reference" title="Aghajanian, S., Worrall, D. M. <strong>Identification and characterization of the gene encoding the human phosphopantetheine adenylyltransferase and dephospho-CoA kinase bifunctional enzyme (CoA synthase).</strong> Biochem. J. 365: 13-18, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11994049/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11994049</a>] [<a href="https://doi.org/10.1042/BJ20020569" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11994049">Aghajanian and Worrall (2002)</a> cloned human COASY. The deduced protein has a calculated molecular mass of 62.3 kD and shares more than 96% amino acid identity with the pig and mouse proteins. <a href="#1" class="mim-tip-reference" title="Aghajanian, S., Worrall, D. M. <strong>Identification and characterization of the gene encoding the human phosphopantetheine adenylyltransferase and dephospho-CoA kinase bifunctional enzyme (CoA synthase).</strong> Biochem. J. 365: 13-18, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11994049/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11994049</a>] [<a href="https://doi.org/10.1042/BJ20020569" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11994049">Aghajanian and Worrall (2002)</a> identified a conserved Walker A-type kinase motif, which is involved in ATP binding, in the C-terminal DPCK domain of COASY. Size-exclusion chromatography showed that recombinant human COASY assumed a monomeric native structure with an apparent molecular mass of 62 kD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11994049" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using full-length ribosomal S6 kinase alpha-II (RPS6KA2; <a href="/entry/601685">601685</a>) as bait in a yeast 2-hybrid screen of a mouse embryo cDNA library, <a href="#9" class="mim-tip-reference" title="Zhyvoloup, A., Nemazanyy, I., Babich, A., Panasyuk, G., Pobigailo, N., Vudmaska, M., Naidenov, V., Kukharenko, O., Palchevskii, S., Savinska, L., Ovcharenko, G., Verdier, F., Valovka, T., Fenton, T., Rebholz, H., Wang, M.-L., Shepherd, P., Matsuka, G., Filonenko, V., Gout, I. T. <strong>Molecular cloning of CoA synthase: the missing link in CoA biosynthesis.</strong> J. Biol. Chem. 277: 22107-22110, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11980892/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11980892</a>] [<a href="https://doi.org/10.1074/jbc.C200195200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11980892">Zhyvoloup et al. (2002)</a> cloned mouse Coasy, which encodes a deduced 563-amino acid protein. Bioinformatic analysis indicated that the N-terminal extension is only present in eukaryotes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11980892" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Nemazanyy, I., Panasyuk, G., Breus, O., Zhyvoloup, A., Filonenko, V., Gout, I. T. <strong>Identification of a novel CoA synthase isoform, which is primarily expressed in the brain.</strong> Biochem. Biophys. Res. Commun. 341: 995-1000, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16460672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16460672</a>] [<a href="https://doi.org/10.1016/j.bbrc.2006.01.051" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16460672">Nemazanyy et al. (2006)</a> identified and cloned a splicing variant of rat CoA synthase, designating it CoASy-beta and the originally identified variant CoASy-alpha. Bioinformatic analysis suggested the presence of a third splice variant, and the authors designated it CoASy-gamma. CoASy-beta encodes the longest isoform, with a 29-amino acid extension at the N terminus of CoASy-alpha. The N-terminal extension did not affect the activity of CoA synthase but possessed a proline-rich sequence. In contrast to the ubiquitous expression of CoASy-alpha in rats, CoASy-beta was expressed primarily in rat brain. Immunofluorescence assays showed that, like CoASy-alpha, CoASy-beta was also localized to the mitochondria of transfected NIH3T3 cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16460672" 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>There are 3 splice variants of human COASY: 60-kD COASY-alpha is ubiquitously expressed; COASY-beta has a 29-amino acid extension at the N terminus and is predominantly expressed in the brain; and COASY-gamma is predicted to code for the C-terminal region of CoA synthase corresponding to DPCK (summary by <a href="#4" class="mim-tip-reference" title="Dusi, S., Valletta, L., Haack, T. B., Tsuchiya, Y., Venco, P., Pasqualato, S., Goffrini, P., Tigano, M., Demchenko, N., Wieland, T., Schwarzmayr, T., Strom, T. M., and 15 others. <strong>Exome sequence reveals mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation.</strong> Am. J. Hum. Genet. 94: 11-22, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24360804/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24360804</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24360804[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.ajhg.2013.11.008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24360804">Dusi et al., 2014</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24360804" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#3" class="mim-tip-reference" title="Daugherty, M., Polanuyer, B., Farrell, M., Scholle, M., Lykidis, A., de Crecy-Lagard, V., Osterman, A. <strong>Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics.</strong> J. Biol. Chem. 277: 21431-21439, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11923312/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11923312</a>] [<a href="https://doi.org/10.1074/jbc.M201708200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11923312">Daugherty et al. (2002)</a> showed that recombinant COASY functioned as the last enzyme within the CoA synthetic pathway, and they verified COASY function by complementation in E. coli. Incubation of PPCS (<a href="/entry/609853">609853</a>), PPCDC (<a href="/entry/609854">609854</a>), and COASY with the necessary substrates and cofactors reconstituted the 4-step biochemical transformation of phosphopantothenate to CoA. Mutation analysis confirmed the bifunctional activity of COASY. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11923312" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Zhyvoloup, A., Nemazanyy, I., Babich, A., Panasyuk, G., Pobigailo, N., Vudmaska, M., Naidenov, V., Kukharenko, O., Palchevskii, S., Savinska, L., Ovcharenko, G., Verdier, F., Valovka, T., Fenton, T., Rebholz, H., Wang, M.-L., Shepherd, P., Matsuka, G., Filonenko, V., Gout, I. T. <strong>Molecular cloning of CoA synthase: the missing link in CoA biosynthesis.</strong> J. Biol. Chem. 277: 22107-22110, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11980892/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11980892</a>] [<a href="https://doi.org/10.1074/jbc.C200195200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11980892">Zhyvoloup et al. (2002)</a> confirmed that mouse Coasy is a bifunctional enzyme. Mutation of his203 to ala in the catalytic pocket of the PPAT domain inactivated PPAT activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11980892" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Zhyvoloup, A., Nemazanyy, I., Panasyuk, G., Valovka, T., Fenton, T., Rebholz, H., Wang, M.-L., Foxon, R., Lyzogubov, V., Usenko, V., Kyyamova, R., Gorbenko, O., Matsuka, G., Filonenko, V., Gout, I. T. <strong>Subcellular localization and regulation of coenzyme A synthase.</strong> J. Biol. Chem. 278: 50316-50321, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14514684/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14514684</a>] [<a href="https://doi.org/10.1074/jbc.M307763200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14514684">Zhyvoloup et al. (2003)</a> demonstrated that full-length CoA synthase is associated with the outer mitochondrial membrane and that the removal of the N-terminal region relocated the enzyme to the cytosol. The activity of CoA synthase was regulated by phospholipids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14514684" 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 HeLa cells, <a href="#4" class="mim-tip-reference" title="Dusi, S., Valletta, L., Haack, T. B., Tsuchiya, Y., Venco, P., Pasqualato, S., Goffrini, P., Tigano, M., Demchenko, N., Wieland, T., Schwarzmayr, T., Strom, T. M., and 15 others. <strong>Exome sequence reveals mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation.</strong> Am. J. Hum. Genet. 94: 11-22, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24360804/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24360804</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24360804[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.ajhg.2013.11.008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24360804">Dusi et al. (2014)</a> determined that the COASY protein is mainly present in the mitochondrial matrix, probably anchored to the inner mitochondrial membrane, but that it is also present in cell lysate. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24360804" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#1" class="mim-tip-reference" title="Aghajanian, S., Worrall, D. M. <strong>Identification and characterization of the gene encoding the human phosphopantetheine adenylyltransferase and dephospho-CoA kinase bifunctional enzyme (CoA synthase).</strong> Biochem. J. 365: 13-18, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11994049/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11994049</a>] [<a href="https://doi.org/10.1042/BJ20020569" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11994049">Aghajanian and Worrall (2002)</a> determined that the COASY gene contains 10 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11994049" 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 genomic sequence analysis, <a href="#1" class="mim-tip-reference" title="Aghajanian, S., Worrall, D. M. <strong>Identification and characterization of the gene encoding the human phosphopantetheine adenylyltransferase and dephospho-CoA kinase bifunctional enzyme (CoA synthase).</strong> Biochem. J. 365: 13-18, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11994049/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11994049</a>] [<a href="https://doi.org/10.1042/BJ20020569" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11994049">Aghajanian and Worrall (2002)</a> mapped the COASY gene to chromosome 17q12-q21. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11994049" 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><strong><em>Neurodegeneration with Brain Iron Accumulation 6</em></strong></p><p>
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In a 25-year-old woman, born of consanguineous Italian parents, with neurodegeneration with brain iron accumulation-6 (NBIA6; <a href="/entry/615643">615643</a>), <a href="#4" class="mim-tip-reference" title="Dusi, S., Valletta, L., Haack, T. B., Tsuchiya, Y., Venco, P., Pasqualato, S., Goffrini, P., Tigano, M., Demchenko, N., Wieland, T., Schwarzmayr, T., Strom, T. M., and 15 others. <strong>Exome sequence reveals mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation.</strong> Am. J. Hum. Genet. 94: 11-22, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24360804/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24360804</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24360804[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.ajhg.2013.11.008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24360804">Dusi et al. (2014)</a> identified a homozygous missense mutation in the COASY gene (R499C; <a href="#0001">609855.0001</a>). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. An unrelated Italian patient with a similar disorder was compound heterozygous for R499C and a nonsense mutation (Q59X; <a href="#0002">609855.0002</a>). This patient was ascertained from a cohort of 280 NBIA-affected individuals in whom the COASY gene was sequenced. In vitro functional expression assays showed that the R499C mutant protein had lost DPCK enzymatic activity. Fibroblasts of both patients showed decreased levels of acetyl coenzyme A (CoA) and significantly decreased de novo production of CoA and dephospho-CoA, at about 20% of controls, consistent with a loss of function. This was the second inborn error of CoA biosynthesis to be implicated in NBIA, the first being NBIA1 (<a href="/entry/234200">234200</a>), which is caused by mutation in the PANK2 gene (<a href="/entry/606157">606157</a>). The phenotype was characterized by progressive motor and cognitive dysfunction beginning in childhood. The patients showed extrapyramidal motor signs, including spasticity, dystonia, and parkinsonism. Brain imaging showed iron accumulation in the basal ganglia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24360804" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 sibs, born of unrelated Turkish parents, with NBIA6, <a href="#5" class="mim-tip-reference" title="Evers, C., Seitz, A., Assmann, B., Opladen, T., Karch, S., Hinderhofer, K., Granzow, M., Paramasivam, N., Eils, R., Diessl, N., Bartram, C. R., Moog, U. <strong>Diagnosis of CoPAN by whole exome sequencing: waking up a sleeping tiger's eye.</strong> Am. J. Med. Genet. 173A: 1878-1886, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28489334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28489334</a>] [<a href="https://doi.org/10.1002/ajmg.a.38252" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28489334">Evers et al. (2017)</a> identified compound heterozygous missense mutations in the COASY gene: the previously identified R499C mutation and A214V (<a href="#0003">609855.0003</a>). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variants were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28489334" 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 a patient, born of consanguineous Italian parents, with NBIA6, <a href="#2" class="mim-tip-reference" title="Annesi, G., Gagliardi, M., Iannello, G., Quattrone, A., Iannello, G., Quattrone, A. <strong>Mutational analysis of COASY in an Italian patient with NBIA.</strong> Parkinsonism Relat. Disord. 28: 150-151, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27021474/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27021474</a>] [<a href="https://doi.org/10.1016/j.parkreldis.2016.03.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27021474">Annesi et al. (2016)</a> identified homozygosity for the R499C mutation in the COASY gene. The parents were heterozygous for the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27021474" 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>Pontocerebellar Hypoplasia Type 12</em></strong></p><p>
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In 4 patients from 2 unrelated families with pontocerebellar hypoplasia type 12 (PCH12; <a href="/entry/618266">618266</a>), <a href="#8" class="mim-tip-reference" title="van Dijk, T., Ferdinandusse, S., Ruiter, J. P. N., Alders, M., Mathijssen, I. B., Parboosingh, J. S., Innes, A. M., Meijers-Heijboer, H., Poll-The, B. T., Bernier, F. P., Wanders, R. J. A., Lamont, R. E., Baas, F. <strong>Biallelic loss of function variants in COASY cause prenatal onset pontocerebellar hypoplasia, microcephaly, and arthrogryposis.</strong> Europ. J. Hum. Genet. 26: 1752-1758, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30089828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30089828</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30089828[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/10.1038/s41431-018-0233-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30089828">van Dijk et al. (2018)</a> identified homozygous or compound heterozygous loss-of-function mutations in the COASY gene (<a href="/entry/600855#0004">600855.0004</a> and <a href="#0005">609855.0005</a>). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. Analysis of patient cells showed no detectable COASY protein and about 1% enzyme activity. Three of the patients were fetuses, and the one live birth died at 1 month of age, suggesting that complete loss of COASY activity is lethal in humans. Noting that CoA is a fundamental cofactor in multiple metabolic processes, <a href="#8" class="mim-tip-reference" title="van Dijk, T., Ferdinandusse, S., Ruiter, J. P. N., Alders, M., Mathijssen, I. B., Parboosingh, J. S., Innes, A. M., Meijers-Heijboer, H., Poll-The, B. T., Bernier, F. P., Wanders, R. J. A., Lamont, R. E., Baas, F. <strong>Biallelic loss of function variants in COASY cause prenatal onset pontocerebellar hypoplasia, microcephaly, and arthrogryposis.</strong> Europ. J. Hum. Genet. 26: 1752-1758, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30089828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30089828</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30089828[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/10.1038/s41431-018-0233-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30089828">van Dijk et al. (2018)</a> suggested that the affected fetuses survived in utero due to maternal CoA supplementation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30089828" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 sibs with PCH12, <a href="#7" class="mim-tip-reference" title="Rosati, J., Johnson, J., Stander, Z., White, A., Tortorelli, S., Bailey, D., Fong, C. T., Lee, B. H. <strong>Progressive brain atrophy and severe neurodevelopmental phenotype in siblings with biallelic COASY variants.</strong> Am. J. Med. Genet. 191A: 842-845, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36495139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36495139</a>] [<a href="https://doi.org/10.1002/ajmg.a.63076" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="36495139">Rosati et al. (2023)</a> identified a homozygous missense mutation in the COASY gene (R555H; <a href="#0006">609855.0006</a>). The mutation, which was identified by whole-genome sequencing, was present in heterozygous state in the parents. Functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36495139" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a 25-year-old woman, born of consanguineous Italian parents, with neurodegeneration with brain iron accumulation-6 (NBIA6; <a href="/entry/615643">615643</a>), <a href="#4" class="mim-tip-reference" title="Dusi, S., Valletta, L., Haack, T. B., Tsuchiya, Y., Venco, P., Pasqualato, S., Goffrini, P., Tigano, M., Demchenko, N., Wieland, T., Schwarzmayr, T., Strom, T. M., and 15 others. <strong>Exome sequence reveals mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation.</strong> Am. J. Hum. Genet. 94: 11-22, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24360804/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24360804</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24360804[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.ajhg.2013.11.008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24360804">Dusi et al. (2014)</a> identified a homozygous c.1495C-T transition (c.1495C-T, NM_025233.6) in the COASY gene, resulting in an arg499-to-cys (R499C) substitution at a highly conserved residue in the nucleotide-binding site of the DPCK domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was found in 1 of 13,005 cases in the Exome Variant Server database. Patient fibroblasts showed decreased levels of the mutant protein compared to control, suggesting that the mutant protein is unstable. An unrelated Italian patient with a similar disorder was compound heterozygous for R499C and a c.175C-T transition, resulting in a gln59-to-ter (Q59X; <a href="#0002">609855.0002</a>) substitution in the N-terminal regulatory region. Each unaffected parent was heterozygous for 1 of the mutations. This patient was ascertained from a cohort of 280 NBIA-affected individuals in whom the COASY gene was sequenced. Analysis of patient cells indicated that the c.175C-T transcript was subject to mRNA decay. In vitro functional expression assays showed that the R499C mutant protein had lost DPCK enzymatic activity. Fibroblasts of both patients showed decreased levels of acetyl CoA compared to controls, although the difference was statistically significant only for the first patient. Fibroblasts from both patients showed significantly decreased de novo production of CoA and dephospho-CoA, at about 20% of controls. Initially, the mutant R499C protein was able to rescue growth in a yeast-null strain, but the strain became auxotrophic for pantothenate and showed reduced growth, suggesting that the mutant enzyme required a higher concentration of pantothenate to produce enough CoA to sustain growth. The findings indicated that a defect in CoA biosynthesis can cause NBIA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24360804" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 sibs, born of unrelated Turkish parents, with NBIA6, <a href="#5" class="mim-tip-reference" title="Evers, C., Seitz, A., Assmann, B., Opladen, T., Karch, S., Hinderhofer, K., Granzow, M., Paramasivam, N., Eils, R., Diessl, N., Bartram, C. R., Moog, U. <strong>Diagnosis of CoPAN by whole exome sequencing: waking up a sleeping tiger's eye.</strong> Am. J. Med. Genet. 173A: 1878-1886, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28489334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28489334</a>] [<a href="https://doi.org/10.1002/ajmg.a.38252" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28489334">Evers et al. (2017)</a> identified compound heterozygous missense mutations in the COASY gene: R499C and A214V (<a href="#0003">609855.0003</a>). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variants were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28489334" 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 a patient, born of consanguineous Italian parents, with NBIA6, <a href="#2" class="mim-tip-reference" title="Annesi, G., Gagliardi, M., Iannello, G., Quattrone, A., Iannello, G., Quattrone, A. <strong>Mutational analysis of COASY in an Italian patient with NBIA.</strong> Parkinsonism Relat. Disord. 28: 150-151, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27021474/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27021474</a>] [<a href="https://doi.org/10.1016/j.parkreldis.2016.03.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27021474">Annesi et al. (2016)</a> identified homozygosity for the R499C mutation in the COASY gene. The parents were heterozygous for the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27021474" 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">rs587777136 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777136;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=rs587777136" 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=rs587777136" 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=RCV000087063" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000087063" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000087063</a>
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<p>For discussion of the c.175C-T transition (c.175C-T, NM_025233.6) in the COASY gene, resulting in a gln59-to-ter (Q59X) mutation, that was found in compound heterozygous state in a patient with neurodegeneration with brain iron accumulation-6 (NBIA6; <a href="/entry/615643">615643</a>) by <a href="#4" class="mim-tip-reference" title="Dusi, S., Valletta, L., Haack, T. B., Tsuchiya, Y., Venco, P., Pasqualato, S., Goffrini, P., Tigano, M., Demchenko, N., Wieland, T., Schwarzmayr, T., Strom, T. M., and 15 others. <strong>Exome sequence reveals mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation.</strong> Am. J. Hum. Genet. 94: 11-22, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24360804/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24360804</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24360804[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.ajhg.2013.11.008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24360804">Dusi et al. (2014)</a>, see <a href="#0001">609855.0001</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24360804" 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">rs1567904066 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1567904066;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=rs1567904066" 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=rs1567904066" 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=RCV000735978" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000735978" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000735978</a>
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<p>In 2 sibs, born of unrelated Turkish parents, with neurodegeneration with brain iron accumulation-6 (NBIA6; <a href="/entry/615643">615643</a>), <a href="#5" class="mim-tip-reference" title="Evers, C., Seitz, A., Assmann, B., Opladen, T., Karch, S., Hinderhofer, K., Granzow, M., Paramasivam, N., Eils, R., Diessl, N., Bartram, C. R., Moog, U. <strong>Diagnosis of CoPAN by whole exome sequencing: waking up a sleeping tiger's eye.</strong> Am. J. Med. Genet. 173A: 1878-1886, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28489334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28489334</a>] [<a href="https://doi.org/10.1002/ajmg.a.38252" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28489334">Evers et al. (2017)</a> identified compound heterozygous missense mutations in the COASY gene: a c.641C-T transition (c.641C-T, NM_001042532.3), resulting in an ala214-to-val (A214V) substitution at a conserved residue in the PPAT domain, and R499C (<a href="#0001">609855.0001</a>). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The variants were filtered against the ExAC database. Functional studies of the variants and studies of patient cells were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28489334" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 PONTOCEREBELLAR HYPOPLASIA, TYPE 12</strong>
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COASY, IVS7AS, C-G, -3
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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> rs577714887 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs577714887;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/rs577714887?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=rs577714887" 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=rs577714887" 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=RCV000735979" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000735979" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000735979</a>
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<p>In 3 deceased sibs, born of consanguineous Pakistani parents (family 2), with pontocerebellar hypoplasia type 12 (PCH12; <a href="/entry/618266">618266</a>), <a href="#8" class="mim-tip-reference" title="van Dijk, T., Ferdinandusse, S., Ruiter, J. P. N., Alders, M., Mathijssen, I. B., Parboosingh, J. S., Innes, A. M., Meijers-Heijboer, H., Poll-The, B. T., Bernier, F. P., Wanders, R. J. A., Lamont, R. E., Baas, F. <strong>Biallelic loss of function variants in COASY cause prenatal onset pontocerebellar hypoplasia, microcephaly, and arthrogryposis.</strong> Europ. J. Hum. Genet. 26: 1752-1758, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30089828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30089828</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30089828[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/10.1038/s41431-018-0233-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30089828">van Dijk et al. (2018)</a> identified a homozygous C-to-G transversion (c.1486-3C-G, NM_025233.6) in intron 7 of the COASY gene. Analysis of patient cells showed that the mutation resulted in a splicing defect, a frameshift, and premature termination (Ala496IlefsTer20) with no detectable protein expression. Enzymatic activity was reduced to about 1% of control levels. The mutation, which was found by a combination of homozygosity mapping and whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The first child died at 1 month of age and the other 2 sibs were found to be affected as fetuses; those pregnancies were terminated. A similarly affected fetus from another family (family 1) was compound heterozygous for the c.1486-3C-G mutation and a 2-bp deletion in exon 8 of the COASY gene (c.1549_1550delAG; <a href="#0005">609855.0005</a>), resulting in a frameshift and premature termination (Ser517ProfsTer61). Cultured amniocytes from this patient showed no detectable COASY protein and severely reduced enzymatic activity, consistent with a loss of function. Each unaffected parent was heterozygous for 1 of the mutations. The 2-bp deletion was not found in the gnomAD database, whereas the splice site mutation was found at a low frequency in heterozygous state (22 of 277,022 alleles). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30089828" 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 PONTOCEREBELLAR HYPOPLASIA, TYPE 12</strong>
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COASY, 2-BP DEL, 1549AG
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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> rs766482965 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs766482965;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/rs766482965?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=rs766482965" 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=rs766482965" 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=RCV000735980 OR RCV001585687 OR RCV003235379" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000735980, RCV001585687, RCV003235379" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000735980...</a>
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<p>For discussion of the 2-bp deletion in exon 8 of the COASY gene (c.1549_1550delAG, NM_025233.6) that was found in compound heterozygous state in a fetus with pontocerebellar hypoplasia type 12 (PCH12; <a href="/entry/618266">618266</a>) by <a href="#8" class="mim-tip-reference" title="van Dijk, T., Ferdinandusse, S., Ruiter, J. P. N., Alders, M., Mathijssen, I. B., Parboosingh, J. S., Innes, A. M., Meijers-Heijboer, H., Poll-The, B. T., Bernier, F. P., Wanders, R. J. A., Lamont, R. E., Baas, F. <strong>Biallelic loss of function variants in COASY cause prenatal onset pontocerebellar hypoplasia, microcephaly, and arthrogryposis.</strong> Europ. J. Hum. Genet. 26: 1752-1758, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30089828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30089828</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30089828[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/10.1038/s41431-018-0233-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30089828">van Dijk et al. (2018)</a>, see <a href="#0004">609855.0004</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30089828" 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 PONTOCEREBELLAR HYPOPLASIA, TYPE 12</strong>
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COASY, ARG555HIS
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV003234983 OR RCV003745567" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV003234983, RCV003745567" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV003234983...</a>
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<p>In 2 sibs with pontocerebellar hypoplasia type 12 (PCH12; <a href="/entry/618266">618266</a>), <a href="#7" class="mim-tip-reference" title="Rosati, J., Johnson, J., Stander, Z., White, A., Tortorelli, S., Bailey, D., Fong, C. T., Lee, B. H. <strong>Progressive brain atrophy and severe neurodevelopmental phenotype in siblings with biallelic COASY variants.</strong> Am. J. Med. Genet. 191A: 842-845, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36495139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36495139</a>] [<a href="https://doi.org/10.1002/ajmg.a.63076" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="36495139">Rosati et al. (2023)</a> identified homozygosity for a c.1664G-A transition (c.1664G-A, NM_025233.6) in the COASY gene, resulting in an arg555-to-his (R555H) substitution. The mutation, which was identified by whole-genome sequencing, was present in heterozygous state in the parents. The variant was present at a low frequency (0.0007%) in only heterozygous state in the gnomAD database. Functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36495139" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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Aghajanian, S., Worrall, D. M.
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<strong>Identification and characterization of the gene encoding the human phosphopantetheine adenylyltransferase and dephospho-CoA kinase bifunctional enzyme (CoA synthase).</strong>
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Biochem. J. 365: 13-18, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11994049/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11994049</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11994049" 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/10.1042/BJ20020569" 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="2" class="mim-anchor"></a>
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<a id="Annesi2016" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Annesi, G., Gagliardi, M., Iannello, G., Quattrone, A., Iannello, G., Quattrone, A.
|
|
<strong>Mutational analysis of COASY in an Italian patient with NBIA.</strong>
|
|
Parkinsonism Relat. Disord. 28: 150-151, 2016.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27021474/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27021474</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27021474" 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.parkreldis.2016.03.011" 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="3" class="mim-anchor"></a>
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<a id="Daugherty2002" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
|
|
Daugherty, M., Polanuyer, B., Farrell, M., Scholle, M., Lykidis, A., de Crecy-Lagard, V., Osterman, A.
|
|
<strong>Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics.</strong>
|
|
J. Biol. Chem. 277: 21431-21439, 2002.
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|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11923312/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11923312</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11923312" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.M201708200" 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="4" class="mim-anchor"></a>
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<a id="Dusi2014" class="mim-anchor"></a>
|
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<div class="">
|
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<p class="mim-text-font">
|
|
Dusi, S., Valletta, L., Haack, T. B., Tsuchiya, Y., Venco, P., Pasqualato, S., Goffrini, P., Tigano, M., Demchenko, N., Wieland, T., Schwarzmayr, T., Strom, T. M., and 15 others.
|
|
<strong>Exome sequence reveals mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation.</strong>
|
|
Am. J. Hum. Genet. 94: 11-22, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24360804/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24360804</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24360804[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=24360804" 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.2013.11.008" 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="5" class="mim-anchor"></a>
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<a id="Evers2017" class="mim-anchor"></a>
|
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<div class="">
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<p class="mim-text-font">
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Evers, C., Seitz, A., Assmann, B., Opladen, T., Karch, S., Hinderhofer, K., Granzow, M., Paramasivam, N., Eils, R., Diessl, N., Bartram, C. R., Moog, U.
|
|
<strong>Diagnosis of CoPAN by whole exome sequencing: waking up a sleeping tiger's eye.</strong>
|
|
Am. J. Med. Genet. 173A: 1878-1886, 2017.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28489334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28489334</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28489334" 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.a.38252" 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="6" class="mim-anchor"></a>
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<a id="Nemazanyy2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Nemazanyy, I., Panasyuk, G., Breus, O., Zhyvoloup, A., Filonenko, V., Gout, I. T.
|
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<strong>Identification of a novel CoA synthase isoform, which is primarily expressed in the brain.</strong>
|
|
Biochem. Biophys. Res. Commun. 341: 995-1000, 2006.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16460672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16460672</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16460672" 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.bbrc.2006.01.051" 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="7" class="mim-anchor"></a>
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<a id="Rosati2023" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
|
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Rosati, J., Johnson, J., Stander, Z., White, A., Tortorelli, S., Bailey, D., Fong, C. T., Lee, B. H.
|
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<strong>Progressive brain atrophy and severe neurodevelopmental phenotype in siblings with biallelic COASY variants.</strong>
|
|
Am. J. Med. Genet. 191A: 842-845, 2023.
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|
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36495139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36495139</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36495139" 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.a.63076" 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="8" class="mim-anchor"></a>
|
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<a id="van Dijk2018" class="mim-anchor"></a>
|
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<div class="">
|
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<p class="mim-text-font">
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van Dijk, T., Ferdinandusse, S., Ruiter, J. P. N., Alders, M., Mathijssen, I. B., Parboosingh, J. S., Innes, A. M., Meijers-Heijboer, H., Poll-The, B. T., Bernier, F. P., Wanders, R. J. A., Lamont, R. E., Baas, F.
|
|
<strong>Biallelic loss of function variants in COASY cause prenatal onset pontocerebellar hypoplasia, microcephaly, and arthrogryposis.</strong>
|
|
Europ. J. Hum. Genet. 26: 1752-1758, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30089828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30089828</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30089828[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=30089828" 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/s41431-018-0233-0" 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="9" class="mim-anchor"></a>
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<a id="Zhyvoloup2002" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zhyvoloup, A., Nemazanyy, I., Babich, A., Panasyuk, G., Pobigailo, N., Vudmaska, M., Naidenov, V., Kukharenko, O., Palchevskii, S., Savinska, L., Ovcharenko, G., Verdier, F., Valovka, T., Fenton, T., Rebholz, H., Wang, M.-L., Shepherd, P., Matsuka, G., Filonenko, V., Gout, I. T.
|
|
<strong>Molecular cloning of CoA synthase: the missing link in CoA biosynthesis.</strong>
|
|
J. Biol. Chem. 277: 22107-22110, 2002.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11980892/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11980892</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11980892" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.C200195200" 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="Zhyvoloup2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
|
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Zhyvoloup, A., Nemazanyy, I., Panasyuk, G., Valovka, T., Fenton, T., Rebholz, H., Wang, M.-L., Foxon, R., Lyzogubov, V., Usenko, V., Kyyamova, R., Gorbenko, O., Matsuka, G., Filonenko, V., Gout, I. T.
|
|
<strong>Subcellular localization and regulation of coenzyme A synthase.</strong>
|
|
J. Biol. Chem. 278: 50316-50321, 2003.
|
|
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14514684/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14514684</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14514684" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.M307763200" target="_blank">Full Text</a>]
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</p>
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</div>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
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Bao Lige - updated : 11/01/2023
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Hilary J. Vernon - updated : 06/20/2023<br>Hilary J. Vernon - updated : 06/15/2023<br>Cassandra L. Kniffin - updated : 01/02/2019
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
|
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Creation Date:
|
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Patricia A. Hartz : 1/27/2006
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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alopez : 11/01/2023
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</span>
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</div>
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</div>
|
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 06/20/2023<br>carol : 06/15/2023<br>carol : 01/10/2019<br>carol : 01/09/2019<br>ckniffin : 01/02/2019<br>mcolton : 08/17/2015<br>carol : 2/17/2014<br>carol : 2/17/2014<br>mcolton : 2/12/2014<br>ckniffin : 2/12/2014<br>mgross : 1/27/2006
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
|
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<span class="mim-font">
|
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<strong>*</strong> 609855
|
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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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|
|
COENZYME A SYNTHASE; COASY
|
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</span>
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</h3>
|
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
|
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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">
|
|
PHOSPHOPANTETHEINE ADENYLYLTRANSFERASE/DEPHOSPHOCOENZYME A KINASE<br />
|
|
PPAT/DPCK
|
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</span>
|
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</h4>
|
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
|
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<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: COASY</em></strong>
|
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</span>
|
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</p>
|
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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|
<strong>SNOMEDCT:</strong> 732264002;
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 17q21.2
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 17:42,562,148-42,566,277 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
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</thead>
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<tbody>
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|
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<tr>
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|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
17q21.2
|
|
</span>
|
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</td>
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<td>
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<span class="mim-font">
|
|
Neurodegeneration with brain iron accumulation 6
|
|
</span>
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</td>
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<td>
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|
<span class="mim-font">
|
|
615643
|
|
</span>
|
|
</td>
|
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<td>
|
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<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
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</td>
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<td>
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<span class="mim-font">
|
|
3
|
|
</span>
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</td>
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</tr>
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<tr>
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<td>
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|
<span class="mim-font">
|
|
Pontocerebellar hypoplasia, type 12
|
|
</span>
|
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</td>
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<td>
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|
<span class="mim-font">
|
|
618266
|
|
</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
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</tbody>
|
|
</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<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">
|
|
<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>Biosynthesis of coenzyme A (CoA) from pantothenic acid (vitamin B5) is an essential universal pathway in prokaryotes and eukaryotes. COASY is a bifunctional enzyme that catalyzes the 2 last steps in CoA synthesis. These activities are performed by 2 separate enzymes, phosphopantetheine adenylyltransferase (PPAT; EC 2.7.7.3) and dephospho-CoA kinase (DPCK; EC 2.7.1.24), in prokaryotes (Daugherty 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">
|
|
<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">
|
|
<p>By searching for sequences similar to E. coli CoA biosynthesis enzymes, followed by PCR of a brain cDNA library, Daugherty et al. (2002) cloned COASY, which they called PPAT/DPCK. The deduced 565-amino acid protein has an N-terminal domain, a central PPAT domain, and a C-terminal DPCK domain. The PPAT domain contains the conserved HxxH motif characteristic of nucleotidyltransferases. Northern blot analysis detected 2.2- and 2.6-kb COASY transcripts in most tissues and tumor cell lines examined. Expression was highest in kidney and liver and lowest in peripheral blood leukocytes. </p><p>By searching for sequences similar to pig Coasy, followed by RT-PCR of a hepatoma cell line cDNA library, Aghajanian and Worrall (2002) cloned human COASY. The deduced protein has a calculated molecular mass of 62.3 kD and shares more than 96% amino acid identity with the pig and mouse proteins. Aghajanian and Worrall (2002) identified a conserved Walker A-type kinase motif, which is involved in ATP binding, in the C-terminal DPCK domain of COASY. Size-exclusion chromatography showed that recombinant human COASY assumed a monomeric native structure with an apparent molecular mass of 62 kD. </p><p>Using full-length ribosomal S6 kinase alpha-II (RPS6KA2; 601685) as bait in a yeast 2-hybrid screen of a mouse embryo cDNA library, Zhyvoloup et al. (2002) cloned mouse Coasy, which encodes a deduced 563-amino acid protein. Bioinformatic analysis indicated that the N-terminal extension is only present in eukaryotes. </p><p>Nemazanyy et al. (2006) identified and cloned a splicing variant of rat CoA synthase, designating it CoASy-beta and the originally identified variant CoASy-alpha. Bioinformatic analysis suggested the presence of a third splice variant, and the authors designated it CoASy-gamma. CoASy-beta encodes the longest isoform, with a 29-amino acid extension at the N terminus of CoASy-alpha. The N-terminal extension did not affect the activity of CoA synthase but possessed a proline-rich sequence. In contrast to the ubiquitous expression of CoASy-alpha in rats, CoASy-beta was expressed primarily in rat brain. Immunofluorescence assays showed that, like CoASy-alpha, CoASy-beta was also localized to the mitochondria of transfected NIH3T3 cells. </p><p>There are 3 splice variants of human COASY: 60-kD COASY-alpha is ubiquitously expressed; COASY-beta has a 29-amino acid extension at the N terminus and is predominantly expressed in the brain; and COASY-gamma is predicted to code for the C-terminal region of CoA synthase corresponding to DPCK (summary by Dusi et al., 2014). </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>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<span class="mim-text-font">
|
|
<p>Daugherty et al. (2002) showed that recombinant COASY functioned as the last enzyme within the CoA synthetic pathway, and they verified COASY function by complementation in E. coli. Incubation of PPCS (609853), PPCDC (609854), and COASY with the necessary substrates and cofactors reconstituted the 4-step biochemical transformation of phosphopantothenate to CoA. Mutation analysis confirmed the bifunctional activity of COASY. </p><p>Zhyvoloup et al. (2002) confirmed that mouse Coasy is a bifunctional enzyme. Mutation of his203 to ala in the catalytic pocket of the PPAT domain inactivated PPAT activity. </p><p>Zhyvoloup et al. (2003) demonstrated that full-length CoA synthase is associated with the outer mitochondrial membrane and that the removal of the N-terminal region relocated the enzyme to the cytosol. The activity of CoA synthase was regulated by phospholipids. </p><p>In HeLa cells, Dusi et al. (2014) determined that the COASY protein is mainly present in the mitochondrial matrix, probably anchored to the inner mitochondrial membrane, but that it is also present in cell lysate. </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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
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</h4>
|
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</div>
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|
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<span class="mim-text-font">
|
|
<p>Aghajanian and Worrall (2002) determined that the COASY gene contains 10 exons. </p>
|
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</span>
|
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<div>
|
|
<br />
|
|
</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
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</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By genomic sequence analysis, Aghajanian and Worrall (2002) mapped the COASY gene to chromosome 17q12-q21. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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|
|
|
|
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
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</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Neurodegeneration with Brain Iron Accumulation 6</em></strong></p><p>
|
|
In a 25-year-old woman, born of consanguineous Italian parents, with neurodegeneration with brain iron accumulation-6 (NBIA6; 615643), Dusi et al. (2014) identified a homozygous missense mutation in the COASY gene (R499C; 609855.0001). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. An unrelated Italian patient with a similar disorder was compound heterozygous for R499C and a nonsense mutation (Q59X; 609855.0002). This patient was ascertained from a cohort of 280 NBIA-affected individuals in whom the COASY gene was sequenced. In vitro functional expression assays showed that the R499C mutant protein had lost DPCK enzymatic activity. Fibroblasts of both patients showed decreased levels of acetyl coenzyme A (CoA) and significantly decreased de novo production of CoA and dephospho-CoA, at about 20% of controls, consistent with a loss of function. This was the second inborn error of CoA biosynthesis to be implicated in NBIA, the first being NBIA1 (234200), which is caused by mutation in the PANK2 gene (606157). The phenotype was characterized by progressive motor and cognitive dysfunction beginning in childhood. The patients showed extrapyramidal motor signs, including spasticity, dystonia, and parkinsonism. Brain imaging showed iron accumulation in the basal ganglia. </p><p>In 2 sibs, born of unrelated Turkish parents, with NBIA6, Evers et al. (2017) identified compound heterozygous missense mutations in the COASY gene: the previously identified R499C mutation and A214V (609855.0003). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variants were not performed. </p><p>In a patient, born of consanguineous Italian parents, with NBIA6, Annesi et al. (2016) identified homozygosity for the R499C mutation in the COASY gene. The parents were heterozygous for the mutation. </p><p><strong><em>Pontocerebellar Hypoplasia Type 12</em></strong></p><p>
|
|
In 4 patients from 2 unrelated families with pontocerebellar hypoplasia type 12 (PCH12; 618266), van Dijk et al. (2018) identified homozygous or compound heterozygous loss-of-function mutations in the COASY gene (600855.0004 and 609855.0005). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. Analysis of patient cells showed no detectable COASY protein and about 1% enzyme activity. Three of the patients were fetuses, and the one live birth died at 1 month of age, suggesting that complete loss of COASY activity is lethal in humans. Noting that CoA is a fundamental cofactor in multiple metabolic processes, van Dijk et al. (2018) suggested that the affected fetuses survived in utero due to maternal CoA supplementation. </p><p>In 2 sibs with PCH12, Rosati et al. (2023) identified a homozygous missense mutation in the COASY gene (R555H; 609855.0006). The mutation, which was identified by whole-genome sequencing, was present in heterozygous state in the parents. Functional studies were not performed. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>6 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 6</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
COASY, ARG499CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs140709867,
|
|
|
|
|
|
gnomAD: rs140709867,
|
|
|
|
|
|
ClinVar: RCV000087062, RCV001588921, RCV002298471
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 25-year-old woman, born of consanguineous Italian parents, with neurodegeneration with brain iron accumulation-6 (NBIA6; 615643), Dusi et al. (2014) identified a homozygous c.1495C-T transition (c.1495C-T, NM_025233.6) in the COASY gene, resulting in an arg499-to-cys (R499C) substitution at a highly conserved residue in the nucleotide-binding site of the DPCK domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was found in 1 of 13,005 cases in the Exome Variant Server database. Patient fibroblasts showed decreased levels of the mutant protein compared to control, suggesting that the mutant protein is unstable. An unrelated Italian patient with a similar disorder was compound heterozygous for R499C and a c.175C-T transition, resulting in a gln59-to-ter (Q59X; 609855.0002) substitution in the N-terminal regulatory region. Each unaffected parent was heterozygous for 1 of the mutations. This patient was ascertained from a cohort of 280 NBIA-affected individuals in whom the COASY gene was sequenced. Analysis of patient cells indicated that the c.175C-T transcript was subject to mRNA decay. In vitro functional expression assays showed that the R499C mutant protein had lost DPCK enzymatic activity. Fibroblasts of both patients showed decreased levels of acetyl CoA compared to controls, although the difference was statistically significant only for the first patient. Fibroblasts from both patients showed significantly decreased de novo production of CoA and dephospho-CoA, at about 20% of controls. Initially, the mutant R499C protein was able to rescue growth in a yeast-null strain, but the strain became auxotrophic for pantothenate and showed reduced growth, suggesting that the mutant enzyme required a higher concentration of pantothenate to produce enough CoA to sustain growth. The findings indicated that a defect in CoA biosynthesis can cause NBIA. </p><p>In 2 sibs, born of unrelated Turkish parents, with NBIA6, Evers et al. (2017) identified compound heterozygous missense mutations in the COASY gene: R499C and A214V (609855.0003). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variants were not performed. </p><p>In a patient, born of consanguineous Italian parents, with NBIA6, Annesi et al. (2016) identified homozygosity for the R499C mutation in the COASY gene. The parents were heterozygous for the mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 6</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
COASY, GLN59TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587777136,
|
|
|
|
|
|
|
|
ClinVar: RCV000087063
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the c.175C-T transition (c.175C-T, NM_025233.6) in the COASY gene, resulting in a gln59-to-ter (Q59X) mutation, that was found in compound heterozygous state in a patient with neurodegeneration with brain iron accumulation-6 (NBIA6; 615643) by Dusi et al. (2014), see 609855.0001. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 6</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
COASY, ALA214VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1567904066,
|
|
|
|
|
|
|
|
ClinVar: RCV000735978
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sibs, born of unrelated Turkish parents, with neurodegeneration with brain iron accumulation-6 (NBIA6; 615643), Evers et al. (2017) identified compound heterozygous missense mutations in the COASY gene: a c.641C-T transition (c.641C-T, NM_001042532.3), resulting in an ala214-to-val (A214V) substitution at a conserved residue in the PPAT domain, and R499C (609855.0001). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The variants were filtered against the ExAC database. Functional studies of the variants and studies of patient cells were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 PONTOCEREBELLAR HYPOPLASIA, TYPE 12</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
COASY, IVS7AS, C-G, -3
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs577714887,
|
|
|
|
|
|
gnomAD: rs577714887,
|
|
|
|
|
|
ClinVar: RCV000735979
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 deceased sibs, born of consanguineous Pakistani parents (family 2), with pontocerebellar hypoplasia type 12 (PCH12; 618266), van Dijk et al. (2018) identified a homozygous C-to-G transversion (c.1486-3C-G, NM_025233.6) in intron 7 of the COASY gene. Analysis of patient cells showed that the mutation resulted in a splicing defect, a frameshift, and premature termination (Ala496IlefsTer20) with no detectable protein expression. Enzymatic activity was reduced to about 1% of control levels. The mutation, which was found by a combination of homozygosity mapping and whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The first child died at 1 month of age and the other 2 sibs were found to be affected as fetuses; those pregnancies were terminated. A similarly affected fetus from another family (family 1) was compound heterozygous for the c.1486-3C-G mutation and a 2-bp deletion in exon 8 of the COASY gene (c.1549_1550delAG; 609855.0005), resulting in a frameshift and premature termination (Ser517ProfsTer61). Cultured amniocytes from this patient showed no detectable COASY protein and severely reduced enzymatic activity, consistent with a loss of function. Each unaffected parent was heterozygous for 1 of the mutations. The 2-bp deletion was not found in the gnomAD database, whereas the splice site mutation was found at a low frequency in heterozygous state (22 of 277,022 alleles). </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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 PONTOCEREBELLAR HYPOPLASIA, TYPE 12</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
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|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
COASY, 2-BP DEL, 1549AG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs766482965,
|
|
|
|
|
|
gnomAD: rs766482965,
|
|
|
|
|
|
ClinVar: RCV000735980, RCV001585687, RCV003235379
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 2-bp deletion in exon 8 of the COASY gene (c.1549_1550delAG, NM_025233.6) that was found in compound heterozygous state in a fetus with pontocerebellar hypoplasia type 12 (PCH12; 618266) by van Dijk et al. (2018), see 609855.0004. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
|
<br />
|
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</div>
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|
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</div>
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<div>
|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 PONTOCEREBELLAR HYPOPLASIA, TYPE 12</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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|
|
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|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
COASY, ARG555HIS
|
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<br />
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|
|
|
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ClinVar: RCV003234983, RCV003745567
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<p>In 2 sibs with pontocerebellar hypoplasia type 12 (PCH12; 618266), Rosati et al. (2023) identified homozygosity for a c.1664G-A transition (c.1664G-A, NM_025233.6) in the COASY gene, resulting in an arg555-to-his (R555H) substitution. The mutation, which was identified by whole-genome sequencing, was present in heterozygous state in the parents. The variant was present at a low frequency (0.0007%) in only heterozygous state in the gnomAD database. Functional studies were not performed. </p>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<p class="mim-text-font">
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Aghajanian, S., Worrall, D. M.
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<strong>Identification and characterization of the gene encoding the human phosphopantetheine adenylyltransferase and dephospho-CoA kinase bifunctional enzyme (CoA synthase).</strong>
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Biochem. J. 365: 13-18, 2002.
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[PubMed: 11994049]
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[Full Text: https://doi.org/10.1042/BJ20020569]
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Annesi, G., Gagliardi, M., Iannello, G., Quattrone, A., Iannello, G., Quattrone, A.
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<strong>Mutational analysis of COASY in an Italian patient with NBIA.</strong>
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Parkinsonism Relat. Disord. 28: 150-151, 2016.
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[PubMed: 27021474]
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[Full Text: https://doi.org/10.1016/j.parkreldis.2016.03.011]
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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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Daugherty, M., Polanuyer, B., Farrell, M., Scholle, M., Lykidis, A., de Crecy-Lagard, V., Osterman, A.
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<strong>Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics.</strong>
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J. Biol. Chem. 277: 21431-21439, 2002.
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[PubMed: 11923312]
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[Full Text: https://doi.org/10.1074/jbc.M201708200]
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Dusi, S., Valletta, L., Haack, T. B., Tsuchiya, Y., Venco, P., Pasqualato, S., Goffrini, P., Tigano, M., Demchenko, N., Wieland, T., Schwarzmayr, T., Strom, T. M., and 15 others.
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<strong>Exome sequence reveals mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation.</strong>
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Am. J. Hum. Genet. 94: 11-22, 2014.
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[PubMed: 24360804]
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[Full Text: https://doi.org/10.1016/j.ajhg.2013.11.008]
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<p class="mim-text-font">
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Evers, C., Seitz, A., Assmann, B., Opladen, T., Karch, S., Hinderhofer, K., Granzow, M., Paramasivam, N., Eils, R., Diessl, N., Bartram, C. R., Moog, U.
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<strong>Diagnosis of CoPAN by whole exome sequencing: waking up a sleeping tiger's eye.</strong>
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Am. J. Med. Genet. 173A: 1878-1886, 2017.
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[PubMed: 28489334]
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[Full Text: https://doi.org/10.1002/ajmg.a.38252]
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<li>
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<p class="mim-text-font">
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Nemazanyy, I., Panasyuk, G., Breus, O., Zhyvoloup, A., Filonenko, V., Gout, I. T.
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<strong>Identification of a novel CoA synthase isoform, which is primarily expressed in the brain.</strong>
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Biochem. Biophys. Res. Commun. 341: 995-1000, 2006.
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[PubMed: 16460672]
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[Full Text: https://doi.org/10.1016/j.bbrc.2006.01.051]
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<li>
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<p class="mim-text-font">
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Rosati, J., Johnson, J., Stander, Z., White, A., Tortorelli, S., Bailey, D., Fong, C. T., Lee, B. H.
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<strong>Progressive brain atrophy and severe neurodevelopmental phenotype in siblings with biallelic COASY variants.</strong>
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Am. J. Med. Genet. 191A: 842-845, 2023.
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[PubMed: 36495139]
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[Full Text: https://doi.org/10.1002/ajmg.a.63076]
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van Dijk, T., Ferdinandusse, S., Ruiter, J. P. N., Alders, M., Mathijssen, I. B., Parboosingh, J. S., Innes, A. M., Meijers-Heijboer, H., Poll-The, B. T., Bernier, F. P., Wanders, R. J. A., Lamont, R. E., Baas, F.
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<strong>Biallelic loss of function variants in COASY cause prenatal onset pontocerebellar hypoplasia, microcephaly, and arthrogryposis.</strong>
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Europ. J. Hum. Genet. 26: 1752-1758, 2018.
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[PubMed: 30089828]
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[Full Text: https://doi.org/10.1038/s41431-018-0233-0]
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Zhyvoloup, A., Nemazanyy, I., Babich, A., Panasyuk, G., Pobigailo, N., Vudmaska, M., Naidenov, V., Kukharenko, O., Palchevskii, S., Savinska, L., Ovcharenko, G., Verdier, F., Valovka, T., Fenton, T., Rebholz, H., Wang, M.-L., Shepherd, P., Matsuka, G., Filonenko, V., Gout, I. T.
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<strong>Molecular cloning of CoA synthase: the missing link in CoA biosynthesis.</strong>
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J. Biol. Chem. 277: 22107-22110, 2002.
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[PubMed: 11980892]
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[Full Text: https://doi.org/10.1074/jbc.C200195200]
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<p class="mim-text-font">
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Zhyvoloup, A., Nemazanyy, I., Panasyuk, G., Valovka, T., Fenton, T., Rebholz, H., Wang, M.-L., Foxon, R., Lyzogubov, V., Usenko, V., Kyyamova, R., Gorbenko, O., Matsuka, G., Filonenko, V., Gout, I. T.
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<strong>Subcellular localization and regulation of coenzyme A synthase.</strong>
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J. Biol. Chem. 278: 50316-50321, 2003.
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[PubMed: 14514684]
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[Full Text: https://doi.org/10.1074/jbc.M307763200]
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<span class="mim-text-font">
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Bao Lige - updated : 11/01/2023<br>Hilary J. Vernon - updated : 06/20/2023<br>Hilary J. Vernon - updated : 06/15/2023<br>Cassandra L. Kniffin - updated : 01/02/2019
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Patricia A. Hartz : 1/27/2006
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alopez : 11/01/2023<br>carol : 06/20/2023<br>carol : 06/15/2023<br>carol : 01/10/2019<br>carol : 01/09/2019<br>ckniffin : 01/02/2019<br>mcolton : 08/17/2015<br>carol : 2/17/2014<br>carol : 2/17/2014<br>mcolton : 2/12/2014<br>ckniffin : 2/12/2014<br>mgross : 1/27/2006
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