3627 lines
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Entry
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- *603707 - MOLYBDENUM COFACTOR SYNTHESIS GENE 1; MOCS1
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- OMIM
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</form>
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*603707</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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</li>
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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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<li role="presentation" style="margin-left: 1em">
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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/603707">Table View</a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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</li>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000124615;t=ENST00000340692" 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=4337" 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=603707" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
|
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000124615;t=ENST00000340692" 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_001075098,NM_001358529,NM_001358530,NM_001358531,NM_001358533,NM_001358534,NM_005943,NR_033233,XM_047418828" 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_001358530" 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=603707" 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=04749&isoform_id=04749_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/MOCS1" 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/2645879,2645880,3559907,3559908,7715056,7715057,7715077,7715079,14970929,14971423,22027536,22477885,30913216,41350403,56204706,56204707,56204708,56204710,56204711,56204712,56204713,56204714,116734668,119624403,119624404,119624405,119624406,119624407,193786976,194390588,1284804782,1284806093,1284806097,1284806140,1284806200,2217361591,2462608632" 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/Q9NZB8" 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=4337" 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=ENSG00000124615;t=ENST00000340692" 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=MOCS1" 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=MOCS1" 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+4337" 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/MOCS1" 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:4337" 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/4337" 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=chr6&hgg_gene=ENST00000340692.10&hgg_start=39904170&hgg_end=39934462&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:7190" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/mocs1" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=603707[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=603707[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000124615" 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=MOCS1" 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=MOCS1" 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=MOCS1" 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=MOCS1&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/PA30900" 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:7190" 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/FBgn0263241.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:1928904" 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/MOCS1#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:1928904" 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/4337/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://omia.org/OMIA001541/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=4337" 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="mim#WormbaseGeneFold" id="mimWormbaseGeneToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes."><span id="mimWormbaseGeneToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Wormbase Gene</div>
|
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<div id="mimWormbaseGeneFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00009885;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00009885 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00009908;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00009908 </a></div>
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</div>
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<div><a href="https://zfin.org/ZDB-GENE-130215-1" 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:4337" 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=MOCS1&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> 1003367004<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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603707
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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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MOLYBDENUM COFACTOR SYNTHESIS GENE 1; MOCS1
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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="includedTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
|
|
Other entities represented in this entry:
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<span class="h3 mim-font">
|
|
MOCS1A, INCLUDED
|
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</span>
|
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</div>
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<div>
|
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<span class="h4 mim-font">
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MOCS1B, INCLUDED
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</span>
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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>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=MOCS1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">MOCS1</a></em></strong>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/6/468?start=-3&limit=10&highlight=468">6p21.2</a>
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr6:39904170-39934462&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'})">6:39,904,170-39,934,462</a> </span>
|
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</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
|
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</p>
|
|
</div>
|
|
|
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
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|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/6/468?start=-3&limit=10&highlight=468">
|
|
6p21.2
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Molybdenum cofactor deficiency A
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/252150"> 252150 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
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</span>
|
|
</td>
|
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<td>
|
|
<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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<p>The MOCS1 gene encodes the first 2 enzymes required in the molybdenum cofactor (MoCo) biosynthesis pathway, MOCS1A and MOCS1B, in a single transcript. The biosynthetic pathway for molybdenum cofactor can be divided into (1) the formation of the unstable precursor Z from GTP, catalyzed by the gene designated MOCS1 (molybdenum cofactor synthesis-1), and (2) the conversion of Z, by molybdopterin synthase (MOCS2; <a href="/entry/603708">603708</a>), into the organic moiety of molybdenum cofactor (<a href="#8" class="mim-tip-reference" title="Reiss, J., Dorche, B., Stallmeyer, B., Mendel, R. R., Cohen, N., Zabot, M. T. <strong>Human molybdopterin synthase gene: genomic structure and mutations in molybdenum cofactor deficiency type B.</strong> Am. J. Hum. Genet. 64: 706-711, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10053004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10053004</a>] [<a href="https://doi.org/10.1086/302296" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10053004">Reiss et al., 1999</a>). A third gene encoding the gephyrin protein (GPHN; <a href="/entry/603930">603930</a>) is required during cofactor assembly for insertion of molybdenum (<a href="#9" class="mim-tip-reference" title="Reiss, J., Johnson, J. L. <strong>Mutations in the molybdenum cofactor biosynthetic genes MOCS1, MOCS2, and GEPH.</strong> Hum. Mutat. 21: 569-576, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12754701/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12754701</a>] [<a href="https://doi.org/10.1002/humu.10223" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12754701">Reiss and Johnson, 2003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12754701+10053004" 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>The genes necessary for the synthesis of the molybdenum cofactor have been characterized in bacteria and plants. The human homologs of these genes were approached as candidate genes for molybdenum cofactor deficiency by <a href="#7" class="mim-tip-reference" title="Reiss, J., Cohen, N., Dorche, C., Mandel, H., Mendel, R. R., Stallmeyer, B., Zabot, M.-T., Dierks, T. <strong>Mutations in a polycistronic nuclear gene associated with molybdenum cofactor deficiency.</strong> Nature Genet. 20: 51-53, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9731530/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9731530</a>] [<a href="https://doi.org/10.1038/1706" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9731530">Reiss et al. (1998)</a>. Using oligonucleotides complementary to a conserved region in the moaA gene of E. coli, they isolated a human cDNA derived from liver mRNA. This transcript contained an open reading frame (ORF) encoding the human moaA homolog and a second ORF encoding the human homolog of a second molybdenum cofactor synthesizing enzyme of E. coli, moaC. The moaA homolog, which the authors referred to as MOCS1A, encodes a protein of 385 amino acids; the moaC homolog, MOCS1B, has 2 possible start codons. The gene encoding both homologs was named MOCS1 for 'molybdenum cofactor synthesis, step 1.' Northern blot analysis detected only full-length transcripts containing both consecutive ORFs in various human tissues. <a href="#7" class="mim-tip-reference" title="Reiss, J., Cohen, N., Dorche, C., Mandel, H., Mendel, R. R., Stallmeyer, B., Zabot, M.-T., Dierks, T. <strong>Mutations in a polycistronic nuclear gene associated with molybdenum cofactor deficiency.</strong> Nature Genet. 20: 51-53, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9731530/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9731530</a>] [<a href="https://doi.org/10.1038/1706" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9731530">Reiss et al. (1998)</a> estimated the transcript size as approximately 3.2 kb. The mRNA structure suggested a translation reinitiation mechanism for the second ORF. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9731530" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Hanzelmann, P., Schwarz, G., Mendel, R. R. <strong>Functionality of alternative splice forms of the first enzymes involved in human molybdenum cofactor biosynthesis.</strong> J. Biol. Chem. 277: 18303-18312, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11891227/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11891227</a>] [<a href="https://doi.org/10.1074/jbc.M200947200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11891227">Hanzelmann et al. (2002)</a> stated that a bicistronic MOCS1 transcript has the potential to encode 2 separate proteins, MOCS1A and MOCS1B, with 385 and 223 amino acids and predicted molecular masses of 43 and 24 kD, respectively. MOCS1A contains 2 highly conserved cysteine clusters, one in the N-terminal region and the other in the C-terminal region. The N-terminal cysteine cluster is the major feature of the radical SAM superfamily harboring a 4Fe-4S cluster, whereas the C-terminal cluster is unique to MOCS1A and is absent in other members of the radical SAM family. In addition to the bicistronic MOCS1 transcript, 2 monocistronic MOCS1 transcripts are produced through alternative splicing. These monocistronic transcripts bypass the termination codon in MOCS1A, resulting in proteins of 636 and 620 amino acids and predicted molecular masses of 70 and 68 kD, respectively, containing both MOCS1A and MOCS1B domains. However, both of these MOCS1A-MOCS1B proteins lack the conserved double-glycine motif at the C-terminal end of MOCS1A. By overexpression analysis in HeLa cells, <a href="#2" class="mim-tip-reference" title="Hanzelmann, P., Schwarz, G., Mendel, R. R. <strong>Functionality of alternative splice forms of the first enzymes involved in human molybdenum cofactor biosynthesis.</strong> J. Biol. Chem. 277: 18303-18312, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11891227/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11891227</a>] [<a href="https://doi.org/10.1074/jbc.M200947200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11891227">Hanzelmann et al. (2002)</a> found that the bicistronic MOCS1 transcript produced only MOCS1A, and not MOCS1B. In contrast, MOCS1B was produced from the monocistronic transcripts, fused to an inactive MOCS1A. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11891227" 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="mim-changed mim-change"><p><a href="#2" class="mim-tip-reference" title="Hanzelmann, P., Schwarz, G., Mendel, R. R. <strong>Functionality of alternative splice forms of the first enzymes involved in human molybdenum cofactor biosynthesis.</strong> J. Biol. Chem. 277: 18303-18312, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11891227/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11891227</a>] [<a href="https://doi.org/10.1074/jbc.M200947200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11891227">Hanzelmann et al. (2002)</a> found that heterologous expression of human MOCS1A and MOCS1B in E. coli resulted in formation of precursor Z. The high level of precursor Z accumulation under the action of MOCS1A indicated that MOCS1A is the rate-limiting enzyme in precursor Z formation. Fusion proteins encoded by the monocistronic MOCS1 transcripts were also functional when heterologously expressed in E. coli. However, only the MOCS1B domain was functionally active in both fusion proteins, and the MOCS1A domain was not. Mutagenesis confirmed that the double-glycine motif at the C terminus of MOCS1A, which is absent in both fusion proteins, is essential and must be accessible for functionality of MOCS1A. Comparative mutation studies of MOCS1A and E. coli MoaD, the ortholog of human MOCS2A, suggested a different function for the double-glycine motifs in both proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11891227" 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></div>
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<p>By heterologous expression in E. coli, <a href="#1" class="mim-tip-reference" title="Hanzelmann, P., Hernandez, H. L., Menzel, C., Garcia-Serres, R., Huynh, B. H., Johnson, M. K., Mendel, R. R., Schindelin, H. <strong>Characterization of MOCS1A, an oxygen-sensitive iron-sulfur protein involved in human molybdenum cofactor biosynthesis.</strong> J. Biol. Chem. 279: 34721-34732, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15180982/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15180982</a>] [<a href="https://doi.org/10.1074/jbc.M313398200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15180982">Hanzelmann et al. (2004)</a> showed that human MOCS1A required the assistance of chaperones and/or proteins for efficient de novo biosynthesis of the FeS clusters for its proper folding and/or insertion of the FeS cluster. Biophysical characterization of purified recombinant protein revealed that MOCS1A was a monomeric protein under anaerobic condition, containing 2 oxygen-sensitive FeS clusters. A redox-active (4Fe-4S)2+ cluster was coordinated by the conserved N-terminal Cx(3)Cx(2)C motif, whereas a (3Fe-4S)0 cluster was coordinated by the conserved C-terminal Cx(2)Cx(13)C motif unique to MOCS1A and its orthologs. Site-directed mutagenesis confirmed the presence of 2 different FeS-binding sites and showed that all 6 cysteines were essential for MOCS1A activity. However, MOCS1A could be reconstituted in vitro to yield a form containing 2 (4Fe-4S)2+ clusters, and both clusters appeared to be degraded via (3Fe-4S)0 and/or (2Fe-2S)2+ cluster intermediates on exposure to oxygen. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15180982" 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="Mayr, S. J., Roper, J., Schwarz, G. <strong>Alternative splicing of the bicistronic gene molybdenum cofactor synthesis 1 (MOCS1) uncovers a novel mitochondrial protein maturation mechanism.</strong> J. Biol. Chem. 295: 3029-3039, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31996372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31996372</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31996372[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1074/jbc.RA119.010720" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31996372">Mayr et al. (2020)</a> noted that alternative splicing of exon 1 of MOCS1 generates 4 bicistronic transcripts encoding isoforms with 4 different N termini. Confocal microscopic analysis showed that MOCS1 isoforms containing exon 1a localized to mitochondrial matrix, whereas those with exon 1b remained in the cytoplasm of transfected COS7 cells. They confirmed that localization to mitochondrial matrix was facilitated by a classical mitochondrial targeting signal encoded by exon 1a. The authors also noted that alternative splicing within exon 9 of MOCS1 produces monocistronic transcripts encoding 2 different MOCS1AB isoforms. Confocal microscopic analysis suggested that exon 10 of MOCS1 encodes an additional mitochondrial translocation signal in the linker region connecting the MOCS1A and MOCS1B domains, as MOCS1AB proteins lacking the classical mitochondrial targeting signal encoded by exon 1a localized to mitochondria in transfected COS7 cells, on the outer side of the outer mitochondrial membrane. Further analysis revealed a novel mitochondrial protein maturation mechanism, in which the MOCS1AB protein was proteolytically cleaved by MPP (<a href="/entry/603131">603131</a>) at position 432 to produce the mature, soluble 188-amino acid MOCS1B protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31996372" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#7" class="mim-tip-reference" title="Reiss, J., Cohen, N., Dorche, C., Mandel, H., Mendel, R. R., Stallmeyer, B., Zabot, M.-T., Dierks, T. <strong>Mutations in a polycistronic nuclear gene associated with molybdenum cofactor deficiency.</strong> Nature Genet. 20: 51-53, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9731530/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9731530</a>] [<a href="https://doi.org/10.1038/1706" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9731530">Reiss et al. (1998)</a> determined that the MOCS1 gene contains 10 exons. MOCS1A is encoded by the first 9 exons; the ORF for MOCS1B is contained in the tenth. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9731530" 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="Reiss, J., Johnson, J. L. <strong>Mutations in the molybdenum cofactor biosynthetic genes MOCS1, MOCS2, and GEPH.</strong> Hum. Mutat. 21: 569-576, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12754701/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12754701</a>] [<a href="https://doi.org/10.1002/humu.10223" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12754701">Reiss and Johnson (2003)</a> stated that the MOCS1 and MOCS2 genes have a bicistronic architecture; i.e., each gene encodes 2 proteins in different ORFs. The protein products MOCS1A and B and MOCS2A and B are expressed either from different mRNAs generated by alternative splicing or by independent translation of a bicistronic mRNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12754701" 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>Confirming results of linkage analysis in patients with MOCOD type A (<a href="#11" class="mim-tip-reference" title="Shalata, A., Mandel, H., Reiss, J., Szargel, R., Cohen-Akenine, A., Dorche, C., Zabot, M.-T., Van Gennip, A., Abeling, N., Berant, M., Cohen, N. <strong>Localization of a gene for molybdenum cofactor deficiency, on the short arm of chromosome 6, by homozygosity mapping.</strong> Am. J. Hum. Genet. 63: 148-154, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9634514/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9634514</a>] [<a href="https://doi.org/10.1086/301916" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9634514">Shalata et al., 1998</a>), <a href="#7" class="mim-tip-reference" title="Reiss, J., Cohen, N., Dorche, C., Mandel, H., Mendel, R. R., Stallmeyer, B., Zabot, M.-T., Dierks, T. <strong>Mutations in a polycistronic nuclear gene associated with molybdenum cofactor deficiency.</strong> Nature Genet. 20: 51-53, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9731530/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9731530</a>] [<a href="https://doi.org/10.1038/1706" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9731530">Reiss et al. (1998)</a> localized the MOCS1 gene to chromosome 6p by fluorescence in situ hybridization using genomic clones. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9731530+9634514" 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>Molybdenum cofactor deficiency is a rare autosomal recessive metabolic disorder characterized by neonatal onset of intractable seizures, opisthotonus, and facial dysmorphism associated with hypouricemia and elevated urinary sulfite levels. Affected individuals show severe neurologic damage and often die in early childhood. The disorder results from decreased activity of sulfite oxidase (SUOX; <a href="/entry/606887">606887</a>) and xanthine dehydrogenase (XDH; <a href="/entry/607633">607633</a>), both of which are dependent upon molybdenum cofactor for activity. In 2 unrelated patients with molybdenum cofactor deficiency type A (MOCODA; <a href="/entry/252150">252150</a>), <a href="#7" class="mim-tip-reference" title="Reiss, J., Cohen, N., Dorche, C., Mandel, H., Mendel, R. R., Stallmeyer, B., Zabot, M.-T., Dierks, T. <strong>Mutations in a polycistronic nuclear gene associated with molybdenum cofactor deficiency.</strong> Nature Genet. 20: 51-53, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9731530/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9731530</a>] [<a href="https://doi.org/10.1038/1706" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9731530">Reiss et al. (1998)</a> identified homozygous truncating mutations in the MOCS1 gene (<a href="#0001">603707.0001</a> and <a href="#0002">603707.0002</a>); one of the mutations occurred in the MOCS1A transcript and the other occurred in the MOCS1B transcript. These findings indicated the existence of a eukaryotic mRNA which, as a single and uniform transcript, guides the synthesis of 2 different enzymatic polypeptides with disease-causing potential. Thus the MOCS1 gene is bicistronic. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9731530" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#6" class="mim-tip-reference" title="Reiss, J., Christensen, E., Kurlemann, G., Zabot, M.-T., Dorche, C. <strong>Genomic structure and mutational spectrum of the bicistronic MOCS1 gene defective in molybdenum cofactor deficiency type A.</strong> Hum. Genet. 103: 639-644, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9921896/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9921896</a>] [<a href="https://doi.org/10.1007/s004390050884" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9921896">Reiss et al. (1998)</a> described the genomic structure of the MOCS1 gene as background for a comprehensive mutation analysis. In an initial cohort of 24 patients with molybdenum cofactor deficiency, they identified 13 different mutations on 34 of the 48 chromosomes, giving a mutation detection rate of 70%. Five mutations were observed in more than 1 patient and together accounted for two-thirds of detected mutations. All patients with identified mutations were either homozygous or compound heterozygous for mutations in either of the 2 open reading frames corresponding to MOCS1A and MOCS1B, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9921896" 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="#9" class="mim-tip-reference" title="Reiss, J., Johnson, J. L. <strong>Mutations in the molybdenum cofactor biosynthetic genes MOCS1, MOCS2, and GEPH.</strong> Hum. Mutat. 21: 569-576, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12754701/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12754701</a>] [<a href="https://doi.org/10.1002/humu.10223" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12754701">Reiss and Johnson (2003)</a> collected a total of 32 different disease-causing mutations in the MOCS1, MOCS2, or GPHN genes, including several common to more than 1 family, that had been identified in molybdenum cofactor-deficient patients and their relatives. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12754701" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#4" class="mim-tip-reference" title="Mayr, S. J., Sass, J. O., Vry, J., Kirschner, J., Mader, I., Hovener, J. B., Reiss, J., Santamaria-Araujo, J. A., Schwarz, G., Grunert, S. C. <strong>A mild case of molybdenum cofactor deficiency defines an alternative route of MOCS1 protein maturation.</strong> J. Inherit. Metab. Dis. 41: 187-196, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29368224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29368224</a>] [<a href="https://doi.org/10.1007/s10545-018-0138-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29368224">Mayr et al. (2018)</a> identified homozygosity for a 1-bp deletion in the MOCS1 gene (c.1338delG; <a href="#0006">603707.0006</a>) in an Afghan patient, born to consanguineous parents, with a mild form of MOCODA. The mutation was predicted to result in a premature termination at residue 477. Sulfite oxidase activity in patient fibroblasts was below the limit of quantitation. Expression of MOCS1 with the c.1338delG mutation in HEK293 cells resulted in 2 proteins, a 50-kD protein consistent with the MOCS1AB truncated protein and a smaller 25-kD protein. The smaller protein was shown to exhibit MOCS1B activity that could fully complement MoaC activity. <a href="#4" class="mim-tip-reference" title="Mayr, S. J., Sass, J. O., Vry, J., Kirschner, J., Mader, I., Hovener, J. B., Reiss, J., Santamaria-Araujo, J. A., Schwarz, G., Grunert, S. C. <strong>A mild case of molybdenum cofactor deficiency defines an alternative route of MOCS1 protein maturation.</strong> J. Inherit. Metab. Dis. 41: 187-196, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29368224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29368224</a>] [<a href="https://doi.org/10.1007/s10545-018-0138-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29368224">Mayr et al. (2018)</a> concluded that only the MOCS1B fragment of the MOCS1AB fusion protein was required for in vivo activity, and the residual enzyme activity afforded by the MOCS1B fragment in this patient provided sufficient activity to permit a mild form of MOCODA. The patient had increased urine xanthine, hypoxanthine, and S-sulfocysteine, but also had some urothione, a Moco degradation product. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29368224" 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="mim-changed mim-change"><p>In a patient with neonatal onset of MOCODA, <a href="#10" class="mim-tip-reference" title="Schwahn, B. C., Hart, C., Smith, L. A., Hart, A., Fairbanks, L., Arenas-Hernandez, M., Turner, C., Horman, A., Rust, S., Santamaria-Araujo, J. A., Mayr, S. J., Schwarz, G., Sharrard, M. <strong>cPMP rescue of a neonate with severe molybdenum cofactor deficiency after serendipitous early diagnosis, and characterisation of a novel MOCS1 variant.</strong> Molec. Genet. Metab. 143: 108598, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/39488078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">39488078</a>] [<a href="https://doi.org/10.1016/j.ymgme.2024.108598" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="39488078">Schwahn et al. (2024)</a> identified compound heterozygous mutations in the MOCS1 gene: a nonsense mutation (R343X; <a href="#0007">603707.0007</a>) in exon 8 and a splice site mutation (c.221-2A-G; <a href="#0008">603707.0008</a>) in intron 1. mRNA sequencing in patient fibroblasts demonstrated only the full-length transcript, and not a smaller transcript missing exon 2, indicating that the transcript arising from the splice site mutation was degraded. Sulfite oxidase activity and sulfite oxidase protein were absent in patient fibroblasts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=39488078" 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></div>
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<strong>8 Selected Examples</a>):</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=603707[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<strong>.0001 MOLYBDENUM COFACTOR DEFICIENCY, TYPE A</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs397518418 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397518418;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=rs397518418" 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=rs397518418" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a patient of Israeli Arab origin whose family showed cosegregation of molybdenum cofactor deficiency (MOCODA; <a href="/entry/252150">252150</a>) with anonymous 6p DNA markers (<a href="#11" class="mim-tip-reference" title="Shalata, A., Mandel, H., Reiss, J., Szargel, R., Cohen-Akenine, A., Dorche, C., Zabot, M.-T., Van Gennip, A., Abeling, N., Berant, M., Cohen, N. <strong>Localization of a gene for molybdenum cofactor deficiency, on the short arm of chromosome 6, by homozygosity mapping.</strong> Am. J. Hum. Genet. 63: 148-154, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9634514/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9634514</a>] [<a href="https://doi.org/10.1086/301916" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9634514">Shalata et al., 1998</a>), <a href="#7" class="mim-tip-reference" title="Reiss, J., Cohen, N., Dorche, C., Mandel, H., Mendel, R. R., Stallmeyer, B., Zabot, M.-T., Dierks, T. <strong>Mutations in a polycistronic nuclear gene associated with molybdenum cofactor deficiency.</strong> Nature Genet. 20: 51-53, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9731530/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9731530</a>] [<a href="https://doi.org/10.1038/1706" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9731530">Reiss et al. (1998)</a> found homozygous deletion of thymine at position 722 in exon 5 of the MOCS1 gene in the MOCS1A transcript. The mutation caused a frameshift that resulted in a stop signal after 5 codons. The truncated protein lacked, among other residues, those at amino acid positions 312, 315, and 329 (encoded by exons 7 and 8), which form a conserved CysxxCys13xCys motif that is essential for moaA function in bacteria, probably by coordinating an FeS complex. The first affected patient in this family was reported by <a href="#12" class="mim-tip-reference" title="Van Gennip, A. H., Mandel, H., Stroomer, L. E., van Cruchten, A. G. <strong>Effect of allopurinol on the xanthinuria in a patient with molybdenum cofactor deficiency.</strong> Adv. Exp. Med. Biol. 370: 375-378, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7660932/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7660932</a>] [<a href="https://doi.org/10.1007/978-1-4615-2584-4_81" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7660932">Van Gennip et al. (1994)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9731530+7660932+9634514" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs397518419 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397518419;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/rs397518419?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=rs397518419" 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=rs397518419" 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=RCV000006492 OR RCV004782010" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006492, RCV004782010" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006492...</a>
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<p>In a Turkish patient with molybdenum cofactor deficiency (MOCODA; <a href="/entry/252150">252150</a>), <a href="#7" class="mim-tip-reference" title="Reiss, J., Cohen, N., Dorche, C., Mandel, H., Mendel, R. R., Stallmeyer, B., Zabot, M.-T., Dierks, T. <strong>Mutations in a polycistronic nuclear gene associated with molybdenum cofactor deficiency.</strong> Nature Genet. 20: 51-53, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9731530/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9731530</a>] [<a href="https://doi.org/10.1038/1706" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9731530">Reiss et al. (1998)</a> identified a 2-bp (AG) deletion (1523_1524delAG) in the MOCS1 gene. The mutation resided in the portion of the gene encoding the second ORF (MOCS1B) homologous to bacterial moaC. The mutation was present in homozygous state; the mutation was identified in heterozygous state in each parent. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9731530" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The 1523_1523delAG mutation results in a frameshift at amino acid 90 of the 223-amino acid MOCS1B. The mutation has also been found in homozygous state in an Italian patient and a second Turkish patient (<a href="#6" class="mim-tip-reference" title="Reiss, J., Christensen, E., Kurlemann, G., Zabot, M.-T., Dorche, C. <strong>Genomic structure and mutational spectrum of the bicistronic MOCS1 gene defective in molybdenum cofactor deficiency type A.</strong> Hum. Genet. 103: 639-644, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9921896/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9921896</a>] [<a href="https://doi.org/10.1007/s004390050884" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9921896">Reiss et al., 1998</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9921896" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 MOLYBDENUM COFACTOR DEFICIENCY, TYPE A</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104893969 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893969;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/rs104893969?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=rs104893969" 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=rs104893969" 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=RCV000006493 OR RCV003407287" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006493, RCV003407287" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006493...</a>
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<p>In a comprehensive search for mutations in the MOCS1 gene in 24 European and Israeli patients with molybdenum cofactor deficiency (MOCODA; <a href="/entry/252150">252150</a>), <a href="#6" class="mim-tip-reference" title="Reiss, J., Christensen, E., Kurlemann, G., Zabot, M.-T., Dorche, C. <strong>Genomic structure and mutational spectrum of the bicistronic MOCS1 gene defective in molybdenum cofactor deficiency type A.</strong> Hum. Genet. 103: 639-644, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9921896/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9921896</a>] [<a href="https://doi.org/10.1007/s004390050884" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9921896">Reiss et al. (1998)</a> found that the arg319-to-gln (R319Q) mutation was the most common mutation, accounting for 14% of MOCOD alleles and 21% of all identified mutations. The mutation was detected exclusively in English patients. The amino acid substitution resulted from a CGA-to-CAA transition in exon 7, which is in the MOCS1A transcript. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9921896" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs141982812 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs141982812;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/rs141982812?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=rs141982812" 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=rs141982812" 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=RCV000006494 OR RCV000732511 OR RCV003914813" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006494, RCV000732511, RCV003914813" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006494...</a>
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<p>In 5 alleles in patients with molybdenum cofactor deficiency (MOCODA; <a href="/entry/252150">252150</a>), <a href="#6" class="mim-tip-reference" title="Reiss, J., Christensen, E., Kurlemann, G., Zabot, M.-T., Dorche, C. <strong>Genomic structure and mutational spectrum of the bicistronic MOCS1 gene defective in molybdenum cofactor deficiency type A.</strong> Hum. Genet. 103: 639-644, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9921896/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9921896</a>] [<a href="https://doi.org/10.1007/s004390050884" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9921896">Reiss et al. (1998)</a> found a G-to-A transition in the first of 2 constitutive positions in the 5-prime splice site junction sequence, leading to skipping of exon 2 of the MOCS1 gene. The mutation was present in compound heterozygous state in 3 patients and in homozygous state in 1. The homozygote and 1 of the compound heterozygotes lived in Denmark; the other 2 compound heterozygotes lived in England. In a Danish family in which 2 sibs were homozygous for the 418+1G-A mutation, <a href="#5" class="mim-tip-reference" title="Reiss, J., Christensen, E., Dorche, C. <strong>Molybdenum cofactor deficiency: first prenatal genetic analysis.</strong> Prenatal Diag. 19: 386-388, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10327149/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10327149</a>] [<a href="https://doi.org/10.1002/(sici)1097-0223(199904)19:4<386::aid-pd550>3.0.co;2-#" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10327149">Reiss et al. (1999)</a> performed prenatal diagnosis, demonstrating heterozygosity in the fetus. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9921896+10327149" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104893970 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893970;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/rs104893970?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=rs104893970" 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=rs104893970" 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=RCV000006495 OR RCV004018578" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006495, RCV004018578" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006495...</a>
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<p><a href="#9" class="mim-tip-reference" title="Reiss, J., Johnson, J. L. <strong>Mutations in the molybdenum cofactor biosynthetic genes MOCS1, MOCS2, and GEPH.</strong> Hum. Mutat. 21: 569-576, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12754701/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12754701</a>] [<a href="https://doi.org/10.1002/humu.10223" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12754701">Reiss and Johnson (2003)</a> suggested that the geographic concentration of the more frequent mutations in the MOCS genes are a consequence of a founder effect. An example is the identification in the MOCS1A gene of mutations arg73 to trp (R73W) and 418+1G-A (<a href="#0004">603707.0004</a>) in families with molybdenum cofactor deficiency (MOCODA; <a href="/entry/252150">252150</a>) from Denmark and the northern part of Germany. A common ancestor born in the 16th century was identified. They referred to these 2 mutations as Nordic mutations, whereas the 1523delAG mutation (<a href="#0002">603707.0002</a>) in the MOCS1B gene, found in Italy, Greece, and Turkey, is primarily a Mediterranean mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12754701" 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 MOLYBDENUM COFACTOR DEFICIENCY, TYPE A</strong>
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<p>In a Afghan patient, born to consanguineous parents, with a mild form of molybdenum cofactor deficiency type A (MOCODA; <a href="/entry/252150">252150</a>), <a href="#4" class="mim-tip-reference" title="Mayr, S. J., Sass, J. O., Vry, J., Kirschner, J., Mader, I., Hovener, J. B., Reiss, J., Santamaria-Araujo, J. A., Schwarz, G., Grunert, S. C. <strong>A mild case of molybdenum cofactor deficiency defines an alternative route of MOCS1 protein maturation.</strong> J. Inherit. Metab. Dis. 41: 187-196, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29368224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29368224</a>] [<a href="https://doi.org/10.1007/s10545-018-0138-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29368224">Mayr et al. (2018)</a> identified homozygosity for a 1-bp deletion (c.1338delG) in the MOCS1 gene, resulting in a frameshift and premature termination (Ser442fs). The mutation was identified by sequencing of molybdenum cofactor-associated genes. The parents were heterozygous for the mutation. The patient had increased urine xanthine, hypoxanthine, and S-sulfocysteine. Sulfite oxidase activity in patient fibroblasts was below the limit of quantitation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29368224" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV003470159" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV003470159" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV003470159</a>
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<div class="mim-changed mim-change"><p>In a patient with neonatal onset of molybdenum cofactor deficiency type A (MOCODA; <a href="/entry/252150">252150</a>), <a href="#10" class="mim-tip-reference" title="Schwahn, B. C., Hart, C., Smith, L. A., Hart, A., Fairbanks, L., Arenas-Hernandez, M., Turner, C., Horman, A., Rust, S., Santamaria-Araujo, J. A., Mayr, S. J., Schwarz, G., Sharrard, M. <strong>cPMP rescue of a neonate with severe molybdenum cofactor deficiency after serendipitous early diagnosis, and characterisation of a novel MOCS1 variant.</strong> Molec. Genet. Metab. 143: 108598, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/39488078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">39488078</a>] [<a href="https://doi.org/10.1016/j.ymgme.2024.108598" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="39488078">Schwahn et al. (2024)</a> identified compound heterozygous mutations in the MOCS1 gene, a c.1027C-T transition in exon 8, resulting in an arg343-to-ter (R343X) substitution, and a c.251-2A-G transition (<a href="#0008">603707.0008</a>) in intron 1, resulting in a splicing defect. The parents were shown to be mutation carriers. Sulfite oxidase activity and sulfite oxidase protein were absent in patient fibroblasts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=39488078" 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></div>
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<strong><div class="mim-changed mim-change">.0008 MOLYBDENUM COFACTOR DEFICIENCY, TYPE A</div></strong>
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<div class="mim-changed mim-change">MOCS1, IVSA1, A-G, -2</div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV004801484" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV004801484" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV004801484</a>
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<div class="mim-changed mim-change"><p>For discussion of the c.251-2A-G transition (<a href="#0008">603707.0008</a>) in intron 1 of the MOCS1 gene, resulting in a splicing defect, that was identified in compound heterozygous state in a patient with neonatal onset of molybdenum cofactor deficiency type A (MOCODA; <a href="/entry/252150">252150</a>) by <a href="#10" class="mim-tip-reference" title="Schwahn, B. C., Hart, C., Smith, L. A., Hart, A., Fairbanks, L., Arenas-Hernandez, M., Turner, C., Horman, A., Rust, S., Santamaria-Araujo, J. A., Mayr, S. J., Schwarz, G., Sharrard, M. <strong>cPMP rescue of a neonate with severe molybdenum cofactor deficiency after serendipitous early diagnosis, and characterisation of a novel MOCS1 variant.</strong> Molec. Genet. Metab. 143: 108598, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/39488078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">39488078</a>] [<a href="https://doi.org/10.1016/j.ymgme.2024.108598" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="39488078">Schwahn et al. (2024)</a>, see <a href="#0007">603707.0007</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=39488078" 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></div>
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<strong>REFERENCES</strong>
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[<a href="https://doi.org/10.1074/jbc.M313398200" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1074/jbc.M200947200" target="_blank">Full Text</a>]
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<strong>Alternative splicing of the bicistronic gene molybdenum cofactor synthesis 1 (MOCS1) uncovers a novel mitochondrial protein maturation mechanism.</strong>
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[<a href="https://doi.org/10.1074/jbc.RA119.010720" target="_blank">Full Text</a>]
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Mayr, S. J., Sass, J. O., Vry, J., Kirschner, J., Mader, I., Hovener, J. B., Reiss, J., Santamaria-Araujo, J. A., Schwarz, G., Grunert, S. C.
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[<a href="https://doi.org/10.1007/s10545-018-0138-7" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/(sici)1097-0223(199904)19:4<386::aid-pd550>3.0.co;2-#" target="_blank">Full Text</a>]
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Reiss, J., Christensen, E., Kurlemann, G., Zabot, M.-T., Dorche, C.
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[<a href="https://doi.org/10.1007/s004390050884" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/1706" target="_blank">Full Text</a>]
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Reiss, J., Dorche, B., Stallmeyer, B., Mendel, R. R., Cohen, N., Zabot, M. T.
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[<a href="https://doi.org/10.1002/humu.10223" target="_blank">Full Text</a>]
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Schwahn, B. C., Hart, C., Smith, L. A., Hart, A., Fairbanks, L., Arenas-Hernandez, M., Turner, C., Horman, A., Rust, S., Santamaria-Araujo, J. A., Mayr, S. J., Schwarz, G., Sharrard, M.
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<strong>cPMP rescue of a neonate with severe molybdenum cofactor deficiency after serendipitous early diagnosis, and characterisation of a novel MOCS1 variant.</strong>
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Molec. Genet. Metab. 143: 108598, 2024.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/39488078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">39488078</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=39488078" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ymgme.2024.108598" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1086/301916" target="_blank">Full Text</a>]
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Van Gennip, A. H., Mandel, H., Stroomer, L. E., van Cruchten, A. G.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7660932/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7660932</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7660932" 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/10.1007/978-1-4615-2584-4_81" target="_blank">Full Text</a>]
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<span class="mim-text-font">
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Hilary J. Vernon - updated : 12/09/2024
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<div class="row collapse" id="mimCollapseContributors">
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<span class="mim-text-font">
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Bao Lige - updated : 06/14/2024<br>Hilary J. Vernon - updated : 05/14/2024<br>Victor A. McKusick - updated : 7/11/2003<br>Victor A. McKusick - updated : 6/8/1999
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<a id="creationDate" class="mim-anchor"></a>
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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<div 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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Victor A. McKusick : 4/8/1999
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 12/20/2024
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<span class="mim-text-font">
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carol : 12/09/2024<br>mgross : 06/14/2024<br>carol : 05/14/2024<br>carol : 05/06/2024<br>carol : 05/12/2015<br>carol : 5/8/2015<br>mcolton : 5/5/2015<br>carol : 11/5/2013<br>carol : 11/4/2013<br>ckniffin : 10/30/2013<br>mgross : 2/3/2009<br>cwells : 7/15/2003<br>cwells : 7/15/2003<br>terry : 7/11/2003<br>terry : 6/8/1999<br>carol : 4/8/1999<br>carol : 4/8/1999
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<h3>
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<span class="mim-font">
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<strong>*</strong> 603707
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<h3>
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<span class="mim-font">
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MOLYBDENUM COFACTOR SYNTHESIS GENE 1; MOCS1
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</h3>
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<span class="mim-font">
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Other entities represented in this entry:
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<span class="h3 mim-font">
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MOCS1A, INCLUDED
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<span class="h4 mim-font">
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MOCS1B, INCLUDED
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: MOCS1</em></strong>
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</span>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 1003367004;
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<strong>
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<em>
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Cytogenetic location: 6p21.2
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Genomic coordinates <span class="small">(GRCh38)</span> : 6:39,904,170-39,934,462 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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<tbody>
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<span class="mim-font">
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6p21.2
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<span class="mim-font">
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Molybdenum cofactor deficiency A
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</td>
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<td>
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<span class="mim-font">
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252150
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<span class="mim-font">
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Autosomal recessive
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<span class="mim-font">
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3
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<span class="mim-font">
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<strong>TEXT</strong>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</h4>
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<span class="mim-text-font">
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<p>The MOCS1 gene encodes the first 2 enzymes required in the molybdenum cofactor (MoCo) biosynthesis pathway, MOCS1A and MOCS1B, in a single transcript. The biosynthetic pathway for molybdenum cofactor can be divided into (1) the formation of the unstable precursor Z from GTP, catalyzed by the gene designated MOCS1 (molybdenum cofactor synthesis-1), and (2) the conversion of Z, by molybdopterin synthase (MOCS2; 603708), into the organic moiety of molybdenum cofactor (Reiss et al., 1999). A third gene encoding the gephyrin protein (GPHN; 603930) is required during cofactor assembly for insertion of molybdenum (Reiss and Johnson, 2003). </p>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</h4>
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<span class="mim-text-font">
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<p>The genes necessary for the synthesis of the molybdenum cofactor have been characterized in bacteria and plants. The human homologs of these genes were approached as candidate genes for molybdenum cofactor deficiency by Reiss et al. (1998). Using oligonucleotides complementary to a conserved region in the moaA gene of E. coli, they isolated a human cDNA derived from liver mRNA. This transcript contained an open reading frame (ORF) encoding the human moaA homolog and a second ORF encoding the human homolog of a second molybdenum cofactor synthesizing enzyme of E. coli, moaC. The moaA homolog, which the authors referred to as MOCS1A, encodes a protein of 385 amino acids; the moaC homolog, MOCS1B, has 2 possible start codons. The gene encoding both homologs was named MOCS1 for 'molybdenum cofactor synthesis, step 1.' Northern blot analysis detected only full-length transcripts containing both consecutive ORFs in various human tissues. Reiss et al. (1998) estimated the transcript size as approximately 3.2 kb. The mRNA structure suggested a translation reinitiation mechanism for the second ORF. </p><p>Hanzelmann et al. (2002) stated that a bicistronic MOCS1 transcript has the potential to encode 2 separate proteins, MOCS1A and MOCS1B, with 385 and 223 amino acids and predicted molecular masses of 43 and 24 kD, respectively. MOCS1A contains 2 highly conserved cysteine clusters, one in the N-terminal region and the other in the C-terminal region. The N-terminal cysteine cluster is the major feature of the radical SAM superfamily harboring a 4Fe-4S cluster, whereas the C-terminal cluster is unique to MOCS1A and is absent in other members of the radical SAM family. In addition to the bicistronic MOCS1 transcript, 2 monocistronic MOCS1 transcripts are produced through alternative splicing. These monocistronic transcripts bypass the termination codon in MOCS1A, resulting in proteins of 636 and 620 amino acids and predicted molecular masses of 70 and 68 kD, respectively, containing both MOCS1A and MOCS1B domains. However, both of these MOCS1A-MOCS1B proteins lack the conserved double-glycine motif at the C-terminal end of MOCS1A. By overexpression analysis in HeLa cells, Hanzelmann et al. (2002) found that the bicistronic MOCS1 transcript produced only MOCS1A, and not MOCS1B. In contrast, MOCS1B was produced from the monocistronic transcripts, fused to an inactive MOCS1A. </p>
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</span>
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<div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Hanzelmann et al. (2002) found that heterologous expression of human MOCS1A and MOCS1B in E. coli resulted in formation of precursor Z. The high level of precursor Z accumulation under the action of MOCS1A indicated that MOCS1A is the rate-limiting enzyme in precursor Z formation. Fusion proteins encoded by the monocistronic MOCS1 transcripts were also functional when heterologously expressed in E. coli. However, only the MOCS1B domain was functionally active in both fusion proteins, and the MOCS1A domain was not. Mutagenesis confirmed that the double-glycine motif at the C terminus of MOCS1A, which is absent in both fusion proteins, is essential and must be accessible for functionality of MOCS1A. Comparative mutation studies of MOCS1A and E. coli MoaD, the ortholog of human MOCS2A, suggested a different function for the double-glycine motifs in both proteins. </p><p>By heterologous expression in E. coli, Hanzelmann et al. (2004) showed that human MOCS1A required the assistance of chaperones and/or proteins for efficient de novo biosynthesis of the FeS clusters for its proper folding and/or insertion of the FeS cluster. Biophysical characterization of purified recombinant protein revealed that MOCS1A was a monomeric protein under anaerobic condition, containing 2 oxygen-sensitive FeS clusters. A redox-active (4Fe-4S)2+ cluster was coordinated by the conserved N-terminal Cx(3)Cx(2)C motif, whereas a (3Fe-4S)0 cluster was coordinated by the conserved C-terminal Cx(2)Cx(13)C motif unique to MOCS1A and its orthologs. Site-directed mutagenesis confirmed the presence of 2 different FeS-binding sites and showed that all 6 cysteines were essential for MOCS1A activity. However, MOCS1A could be reconstituted in vitro to yield a form containing 2 (4Fe-4S)2+ clusters, and both clusters appeared to be degraded via (3Fe-4S)0 and/or (2Fe-2S)2+ cluster intermediates on exposure to oxygen. </p><p>Mayr et al. (2020) noted that alternative splicing of exon 1 of MOCS1 generates 4 bicistronic transcripts encoding isoforms with 4 different N termini. Confocal microscopic analysis showed that MOCS1 isoforms containing exon 1a localized to mitochondrial matrix, whereas those with exon 1b remained in the cytoplasm of transfected COS7 cells. They confirmed that localization to mitochondrial matrix was facilitated by a classical mitochondrial targeting signal encoded by exon 1a. The authors also noted that alternative splicing within exon 9 of MOCS1 produces monocistronic transcripts encoding 2 different MOCS1AB isoforms. Confocal microscopic analysis suggested that exon 10 of MOCS1 encodes an additional mitochondrial translocation signal in the linker region connecting the MOCS1A and MOCS1B domains, as MOCS1AB proteins lacking the classical mitochondrial targeting signal encoded by exon 1a localized to mitochondria in transfected COS7 cells, on the outer side of the outer mitochondrial membrane. Further analysis revealed a novel mitochondrial protein maturation mechanism, in which the MOCS1AB protein was proteolytically cleaved by MPP (603131) at position 432 to produce the mature, soluble 188-amino acid MOCS1B protein. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Reiss et al. (1998) determined that the MOCS1 gene contains 10 exons. MOCS1A is encoded by the first 9 exons; the ORF for MOCS1B is contained in the tenth. </p><p>Reiss and Johnson (2003) stated that the MOCS1 and MOCS2 genes have a bicistronic architecture; i.e., each gene encodes 2 proteins in different ORFs. The protein products MOCS1A and B and MOCS2A and B are expressed either from different mRNAs generated by alternative splicing or by independent translation of a bicistronic mRNA. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Confirming results of linkage analysis in patients with MOCOD type A (Shalata et al., 1998), Reiss et al. (1998) localized the MOCS1 gene to chromosome 6p by fluorescence in situ hybridization using genomic clones. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Molybdenum cofactor deficiency is a rare autosomal recessive metabolic disorder characterized by neonatal onset of intractable seizures, opisthotonus, and facial dysmorphism associated with hypouricemia and elevated urinary sulfite levels. Affected individuals show severe neurologic damage and often die in early childhood. The disorder results from decreased activity of sulfite oxidase (SUOX; 606887) and xanthine dehydrogenase (XDH; 607633), both of which are dependent upon molybdenum cofactor for activity. In 2 unrelated patients with molybdenum cofactor deficiency type A (MOCODA; 252150), Reiss et al. (1998) identified homozygous truncating mutations in the MOCS1 gene (603707.0001 and 603707.0002); one of the mutations occurred in the MOCS1A transcript and the other occurred in the MOCS1B transcript. These findings indicated the existence of a eukaryotic mRNA which, as a single and uniform transcript, guides the synthesis of 2 different enzymatic polypeptides with disease-causing potential. Thus the MOCS1 gene is bicistronic. </p><p>Reiss et al. (1998) described the genomic structure of the MOCS1 gene as background for a comprehensive mutation analysis. In an initial cohort of 24 patients with molybdenum cofactor deficiency, they identified 13 different mutations on 34 of the 48 chromosomes, giving a mutation detection rate of 70%. Five mutations were observed in more than 1 patient and together accounted for two-thirds of detected mutations. All patients with identified mutations were either homozygous or compound heterozygous for mutations in either of the 2 open reading frames corresponding to MOCS1A and MOCS1B, respectively. </p><p>Reiss and Johnson (2003) collected a total of 32 different disease-causing mutations in the MOCS1, MOCS2, or GPHN genes, including several common to more than 1 family, that had been identified in molybdenum cofactor-deficient patients and their relatives. </p><p>Mayr et al. (2018) identified homozygosity for a 1-bp deletion in the MOCS1 gene (c.1338delG; 603707.0006) in an Afghan patient, born to consanguineous parents, with a mild form of MOCODA. The mutation was predicted to result in a premature termination at residue 477. Sulfite oxidase activity in patient fibroblasts was below the limit of quantitation. Expression of MOCS1 with the c.1338delG mutation in HEK293 cells resulted in 2 proteins, a 50-kD protein consistent with the MOCS1AB truncated protein and a smaller 25-kD protein. The smaller protein was shown to exhibit MOCS1B activity that could fully complement MoaC activity. Mayr et al. (2018) concluded that only the MOCS1B fragment of the MOCS1AB fusion protein was required for in vivo activity, and the residual enzyme activity afforded by the MOCS1B fragment in this patient provided sufficient activity to permit a mild form of MOCODA. The patient had increased urine xanthine, hypoxanthine, and S-sulfocysteine, but also had some urothione, a Moco degradation product. </p><p>In a patient with neonatal onset of MOCODA, Schwahn et al. (2024) identified compound heterozygous mutations in the MOCS1 gene: a nonsense mutation (R343X; 603707.0007) in exon 8 and a splice site mutation (c.221-2A-G; 603707.0008) in intron 1. mRNA sequencing in patient fibroblasts demonstrated only the full-length transcript, and not a smaller transcript missing exon 2, indicating that the transcript arising from the splice site mutation was degraded. Sulfite oxidase activity and sulfite oxidase protein were absent in patient fibroblasts. </p>
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</span>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>8 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 MOLYBDENUM COFACTOR DEFICIENCY, TYPE A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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MOCS1, 1-BP DEL, 722T
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<br />
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SNP: rs397518418,
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ClinVar: RCV000006491
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient of Israeli Arab origin whose family showed cosegregation of molybdenum cofactor deficiency (MOCODA; 252150) with anonymous 6p DNA markers (Shalata et al., 1998), Reiss et al. (1998) found homozygous deletion of thymine at position 722 in exon 5 of the MOCS1 gene in the MOCS1A transcript. The mutation caused a frameshift that resulted in a stop signal after 5 codons. The truncated protein lacked, among other residues, those at amino acid positions 312, 315, and 329 (encoded by exons 7 and 8), which form a conserved CysxxCys13xCys motif that is essential for moaA function in bacteria, probably by coordinating an FeS complex. The first affected patient in this family was reported by Van Gennip et al. (1994). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 MOLYBDENUM COFACTOR DEFICIENCY, TYPE A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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MOCS1, 2-BP DEL, 1523AG
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<br />
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SNP: rs397518419,
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gnomAD: rs397518419,
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ClinVar: RCV000006492, RCV004782010
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a Turkish patient with molybdenum cofactor deficiency (MOCODA; 252150), Reiss et al. (1998) identified a 2-bp (AG) deletion (1523_1524delAG) in the MOCS1 gene. The mutation resided in the portion of the gene encoding the second ORF (MOCS1B) homologous to bacterial moaC. The mutation was present in homozygous state; the mutation was identified in heterozygous state in each parent. </p><p>The 1523_1523delAG mutation results in a frameshift at amino acid 90 of the 223-amino acid MOCS1B. The mutation has also been found in homozygous state in an Italian patient and a second Turkish patient (Reiss et al., 1998). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 MOLYBDENUM COFACTOR DEFICIENCY, TYPE A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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MOCS1, ARG319GLN
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<br />
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SNP: rs104893969,
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gnomAD: rs104893969,
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ClinVar: RCV000006493, RCV003407287
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a comprehensive search for mutations in the MOCS1 gene in 24 European and Israeli patients with molybdenum cofactor deficiency (MOCODA; 252150), Reiss et al. (1998) found that the arg319-to-gln (R319Q) mutation was the most common mutation, accounting for 14% of MOCOD alleles and 21% of all identified mutations. The mutation was detected exclusively in English patients. The amino acid substitution resulted from a CGA-to-CAA transition in exon 7, which is in the MOCS1A transcript. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 MOLYBDENUM COFACTOR DEFICIENCY, TYPE A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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MOCS1, IVS2DS, G-A, +1
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<br />
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SNP: rs141982812,
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gnomAD: rs141982812,
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ClinVar: RCV000006494, RCV000732511, RCV003914813
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 5 alleles in patients with molybdenum cofactor deficiency (MOCODA; 252150), Reiss et al. (1998) found a G-to-A transition in the first of 2 constitutive positions in the 5-prime splice site junction sequence, leading to skipping of exon 2 of the MOCS1 gene. The mutation was present in compound heterozygous state in 3 patients and in homozygous state in 1. The homozygote and 1 of the compound heterozygotes lived in Denmark; the other 2 compound heterozygotes lived in England. In a Danish family in which 2 sibs were homozygous for the 418+1G-A mutation, Reiss et al. (1999) performed prenatal diagnosis, demonstrating heterozygosity in the fetus. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0005 MOLYBDENUM COFACTOR DEFICIENCY, TYPE A</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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MOCS1, ARG73TRP
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<br />
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SNP: rs104893970,
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gnomAD: rs104893970,
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ClinVar: RCV000006495, RCV004018578
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>Reiss and Johnson (2003) suggested that the geographic concentration of the more frequent mutations in the MOCS genes are a consequence of a founder effect. An example is the identification in the MOCS1A gene of mutations arg73 to trp (R73W) and 418+1G-A (603707.0004) in families with molybdenum cofactor deficiency (MOCODA; 252150) from Denmark and the northern part of Germany. A common ancestor born in the 16th century was identified. They referred to these 2 mutations as Nordic mutations, whereas the 1523delAG mutation (603707.0002) in the MOCS1B gene, found in Italy, Greece, and Turkey, is primarily a Mediterranean mutation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 MOLYBDENUM COFACTOR DEFICIENCY, TYPE A</strong>
|
|
</span>
|
|
</h4>
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</div>
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<div>
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<span class="mim-text-font">
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MOCS1, 1-BP DEL, 1338G
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<br />
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ClinVar: RCV004555145
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</span>
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|
</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a Afghan patient, born to consanguineous parents, with a mild form of molybdenum cofactor deficiency type A (MOCODA; 252150), Mayr et al. (2018) identified homozygosity for a 1-bp deletion (c.1338delG) in the MOCS1 gene, resulting in a frameshift and premature termination (Ser442fs). The mutation was identified by sequencing of molybdenum cofactor-associated genes. The parents were heterozygous for the mutation. The patient had increased urine xanthine, hypoxanthine, and S-sulfocysteine. Sulfite oxidase activity in patient fibroblasts was below the limit of quantitation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 MOLYBDENUM COFACTOR DEFICIENCY, TYPE A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
|
MOCS1, ARG343TER
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|
<br />
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|
|
ClinVar: RCV003470159
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<div class="mim-changed mim-change"><p>In a patient with neonatal onset of molybdenum cofactor deficiency type A (MOCODA; 252150), Schwahn et al. (2024) identified compound heterozygous mutations in the MOCS1 gene, a c.1027C-T transition in exon 8, resulting in an arg343-to-ter (R343X) substitution, and a c.251-2A-G transition (603707.0008) in intron 1, resulting in a splicing defect. The parents were shown to be mutation carriers. Sulfite oxidase activity and sulfite oxidase protein were absent in patient fibroblasts. </p></div>
|
|
</span>
|
|
</div>
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<div>
|
|
<br />
|
|
</div>
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|
|
</div>
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|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 MOLYBDENUM COFACTOR DEFICIENCY, TYPE A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
MOCS1, IVSA1, A-G, -2
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV004801484
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<div class="mim-changed mim-change"><p>For discussion of the c.251-2A-G transition (603707.0008) in intron 1 of the MOCS1 gene, resulting in a splicing defect, that was identified in compound heterozygous state in a patient with neonatal onset of molybdenum cofactor deficiency type A (MOCODA; 252150) by Schwahn et al. (2024), see 603707.0007. </p></div>
|
|
</span>
|
|
</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
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<div>
|
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<ol>
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<li>
|
|
<p class="mim-text-font">
|
|
Hanzelmann, P., Hernandez, H. L., Menzel, C., Garcia-Serres, R., Huynh, B. H., Johnson, M. K., Mendel, R. R., Schindelin, H.
|
|
<strong>Characterization of MOCS1A, an oxygen-sensitive iron-sulfur protein involved in human molybdenum cofactor biosynthesis.</strong>
|
|
J. Biol. Chem. 279: 34721-34732, 2004.
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|
[PubMed: 15180982]
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[Full Text: https://doi.org/10.1074/jbc.M313398200]
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Hanzelmann, P., Schwarz, G., Mendel, R. R.
|
|
<strong>Functionality of alternative splice forms of the first enzymes involved in human molybdenum cofactor biosynthesis.</strong>
|
|
J. Biol. Chem. 277: 18303-18312, 2002.
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|
|
[PubMed: 11891227]
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[Full Text: https://doi.org/10.1074/jbc.M200947200]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Mayr, S. J., Roper, J., Schwarz, G.
|
|
<strong>Alternative splicing of the bicistronic gene molybdenum cofactor synthesis 1 (MOCS1) uncovers a novel mitochondrial protein maturation mechanism.</strong>
|
|
J. Biol. Chem. 295: 3029-3039, 2020.
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[PubMed: 31996372]
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[Full Text: https://doi.org/10.1074/jbc.RA119.010720]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Mayr, S. J., Sass, J. O., Vry, J., Kirschner, J., Mader, I., Hovener, J. B., Reiss, J., Santamaria-Araujo, J. A., Schwarz, G., Grunert, S. C.
|
|
<strong>A mild case of molybdenum cofactor deficiency defines an alternative route of MOCS1 protein maturation.</strong>
|
|
J. Inherit. Metab. Dis. 41: 187-196, 2018.
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|
[PubMed: 29368224]
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[Full Text: https://doi.org/10.1007/s10545-018-0138-7]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Reiss, J., Christensen, E., Dorche, C.
|
|
<strong>Molybdenum cofactor deficiency: first prenatal genetic analysis.</strong>
|
|
Prenatal Diag. 19: 386-388, 1999.
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|
|
[PubMed: 10327149]
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[Full Text: https://doi.org/10.1002/(sici)1097-0223(199904)19:4<386::aid-pd550>3.0.co;2-#]
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Reiss, J., Christensen, E., Kurlemann, G., Zabot, M.-T., Dorche, C.
|
|
<strong>Genomic structure and mutational spectrum of the bicistronic MOCS1 gene defective in molybdenum cofactor deficiency type A.</strong>
|
|
Hum. Genet. 103: 639-644, 1998.
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|
|
[PubMed: 9921896]
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[Full Text: https://doi.org/10.1007/s004390050884]
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Reiss, J., Cohen, N., Dorche, C., Mandel, H., Mendel, R. R., Stallmeyer, B., Zabot, M.-T., Dierks, T.
|
|
<strong>Mutations in a polycistronic nuclear gene associated with molybdenum cofactor deficiency.</strong>
|
|
Nature Genet. 20: 51-53, 1998.
|
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|
|
[PubMed: 9731530]
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|
|
[Full Text: https://doi.org/10.1038/1706]
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Reiss, J., Dorche, B., Stallmeyer, B., Mendel, R. R., Cohen, N., Zabot, M. T.
|
|
<strong>Human molybdopterin synthase gene: genomic structure and mutations in molybdenum cofactor deficiency type B.</strong>
|
|
Am. J. Hum. Genet. 64: 706-711, 1999.
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|
|
[PubMed: 10053004]
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[Full Text: https://doi.org/10.1086/302296]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Reiss, J., Johnson, J. L.
|
|
<strong>Mutations in the molybdenum cofactor biosynthetic genes MOCS1, MOCS2, and GEPH.</strong>
|
|
Hum. Mutat. 21: 569-576, 2003.
|
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|
|
[PubMed: 12754701]
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|
|
[Full Text: https://doi.org/10.1002/humu.10223]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Schwahn, B. C., Hart, C., Smith, L. A., Hart, A., Fairbanks, L., Arenas-Hernandez, M., Turner, C., Horman, A., Rust, S., Santamaria-Araujo, J. A., Mayr, S. J., Schwarz, G., Sharrard, M.
|
|
<strong>cPMP rescue of a neonate with severe molybdenum cofactor deficiency after serendipitous early diagnosis, and characterisation of a novel MOCS1 variant.</strong>
|
|
Molec. Genet. Metab. 143: 108598, 2024.
|
|
|
|
|
|
[PubMed: 39488078]
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|
[Full Text: https://doi.org/10.1016/j.ymgme.2024.108598]
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Shalata, A., Mandel, H., Reiss, J., Szargel, R., Cohen-Akenine, A., Dorche, C., Zabot, M.-T., Van Gennip, A., Abeling, N., Berant, M., Cohen, N.
|
|
<strong>Localization of a gene for molybdenum cofactor deficiency, on the short arm of chromosome 6, by homozygosity mapping.</strong>
|
|
Am. J. Hum. Genet. 63: 148-154, 1998.
|
|
|
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|
|
[PubMed: 9634514]
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|
|
[Full Text: https://doi.org/10.1086/301916]
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Van Gennip, A. H., Mandel, H., Stroomer, L. E., van Cruchten, A. G.
|
|
<strong>Effect of allopurinol on the xanthinuria in a patient with molybdenum cofactor deficiency.</strong>
|
|
Adv. Exp. Med. Biol. 370: 375-378, 1994.
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|
|
[PubMed: 7660932]
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|
|
[Full Text: https://doi.org/10.1007/978-1-4615-2584-4_81]
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</p>
|
|
</li>
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</ol>
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<div>
|
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<br />
|
|
</div>
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</div>
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</div>
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<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
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Hilary J. Vernon - updated : 12/09/2024<br>Bao Lige - updated : 06/14/2024<br>Hilary J. Vernon - updated : 05/14/2024<br>Victor A. McKusick - updated : 7/11/2003<br>Victor A. McKusick - updated : 6/8/1999
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Victor A. McKusick : 4/8/1999
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