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Entry
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- *108370 - ASPARAGINE SYNTHETASE; ASNS
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*108370</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<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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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#geneFunction">Gene Function</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/108370">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<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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<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 id="mimExternalLinksFold" class="collapse in">
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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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<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=ENSG00000070669;t=ENST00000394308" 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=440" 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=108370" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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<div class="panel 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=ENSG00000070669;t=ENST00000394308" 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_001178075,NM_001178076,NM_001178077,NM_001352496,NM_001673,NM_133436,NM_183356" 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_001673" 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=108370" 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=00153&isoform_id=00153_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/ASNS" 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/179100,339987,533200,703119,13432102,14250542,15779114,30583065,37674405,51094870,119597129,119597136,119597137,119597138,119597139,168229248,168229250,168229252,194378776,194378858,221045836,296010848,296010850,296010852,1206655258" 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/P08243" 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=440" 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=ENSG00000070669;t=ENST00000394308" 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=ASNS" 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=ASNS" 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+440" 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/ASNS" 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:440" 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/440" 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=chr7&hgg_gene=ENST00000394308.8&hgg_start=97851677&hgg_end=97928441&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 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:753" 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/asns" 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=108370[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=108370[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/ASNS/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000070669" 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=ASNS" 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=ASNS" 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=ASNS" 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=ASNS&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/PA25052" 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:753" 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/FBgn0270926.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:1350929" 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/ASNS#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:1350929" 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/440/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=440" 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=WBGene00003816;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00003816 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00019730;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00019730 </a></div>
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</div>
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<div><a href="https://zfin.org/ZDB-GENE-040426-1091" 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:440" 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=ASNS&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> 782757004<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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108370
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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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ASPARAGINE SYNTHETASE; ASNS
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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HUMAN COMPLEMENT FOR HAMSTER TEMPERATURE-SENSITIVE MUTANT ts11
|
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</span>
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</h4>
|
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=ASNS" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">ASNS</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/7/440?start=-3&limit=10&highlight=440">7q21.3</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr7:97851677-97928441&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'})">7:97,851,677-97,928,441</a> </span>
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</em>
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</strong>
|
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
|
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<br />
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</div>
|
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<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
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<tr class="active">
|
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<th>
|
|
Location
|
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</th>
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<th>
|
|
Phenotype
|
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</th>
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<th>
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|
Phenotype <br /> MIM number
|
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</th>
|
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<th>
|
|
Inheritance
|
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</th>
|
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<th>
|
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Phenotype <br /> mapping key
|
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</th>
|
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</tr>
|
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</thead>
|
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<tbody>
|
|
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|
<tr>
|
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<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/7/440?start=-3&limit=10&highlight=440">
|
|
7q21.3
|
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</a>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
Asparagine synthetase deficiency
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
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|
<a href="/entry/615574"> 615574 </a>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/108370" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/108370" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
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<p>The ASNS gene encodes asparagine synthetase (<a href="https://enzyme.expasy.org/EC/6.3.5.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 6.3.5.4</a>), an enzyme that catalyzes the transfer of ammonia from glutamine to aspartic acid to form asparagine. It is expressed in most mammalian cells (summary by <a href="#12" class="mim-tip-reference" title="Zhang, Y. P., Lambert, M. A., Cairney, A. E. L., Wills, D., Ray, P. N., Andrulis, I. L. <strong>Molecular structure of the human asparagine synthetase gene.</strong> Genomics 4: 259-265, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2565875/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2565875</a>] [<a href="https://doi.org/10.1016/0888-7543(89)90329-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2565875">Zhang et al., 1989</a> and <a href="#8" class="mim-tip-reference" title="Ruzzo, E. K., Capo-Chichi, J.-M., Ben-Zeev, B., Chitayat, D., Mao, H., Pappas, A. L., Hitomi, Y., Lu, Y.-F., Yao, X., Hamdan, F. F., Pelak, K., Reznik-Wolf, H., and 32 others. <strong>Deficiency of asparagine synthetase causes congenital microcephaly and a progressive form of encephalopathy.</strong> Neuron 80: 429-441, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24139043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24139043</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24139043[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.neuron.2013.08.013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24139043">Ruzzo et al., 2013</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2565875+24139043" 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="Greco, A., Ittmann, M., Basilico, C. <strong>Molecular cloning of a gene that is necessary for G(1) progression in mammalian cells.</strong> Proc. Nat. Acad. Sci. 84: 1565-1569, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3470743/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3470743</a>] [<a href="https://doi.org/10.1073/pnas.84.6.1565" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3470743">Greco et al. (1987)</a> cloned human ASNS based on its ability to complement ts11, a temperature-sensitive (ts) mutant of the BHK hamster cell line that at the nonpermissive temperature is blocked in progression through the G1 phase of the cell growth cycle. The gene was transcribed into an mRNA of 2 kb that was expressed in all human, hamster, and mouse cell lines tested. It encodes a protein of about 550 amino acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3470743" 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>Asns is highly expressed in the adult mouse brain. <a href="#8" class="mim-tip-reference" title="Ruzzo, E. K., Capo-Chichi, J.-M., Ben-Zeev, B., Chitayat, D., Mao, H., Pappas, A. L., Hitomi, Y., Lu, Y.-F., Yao, X., Hamdan, F. F., Pelak, K., Reznik-Wolf, H., and 32 others. <strong>Deficiency of asparagine synthetase causes congenital microcephaly and a progressive form of encephalopathy.</strong> Neuron 80: 429-441, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24139043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24139043</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24139043[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.neuron.2013.08.013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24139043">Ruzzo et al. (2013)</a> found that Asns is also expressed in the developing embryonic mouse brain in the cortical plate and the ventricular and subventricular zones where neural progenitors reside. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24139043" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#12" class="mim-tip-reference" title="Zhang, Y. P., Lambert, M. A., Cairney, A. E. L., Wills, D., Ray, P. N., Andrulis, I. L. <strong>Molecular structure of the human asparagine synthetase gene.</strong> Genomics 4: 259-265, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2565875/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2565875</a>] [<a href="https://doi.org/10.1016/0888-7543(89)90329-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2565875">Zhang et al. (1989)</a> demonstrated that the ASNS gene spans 35 kb and contains 13 exons. The 5-prime upstream region of this gene, like other housekeeping genes, lacks conventional TATA and CAAT boxes. Both the human and the hamster genes have a high 5-prime G+C content which may play a role in expression through DNA methylation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2565875" 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 gene for ASNS has been assigned to chromosome 7 by enzymatic analyses of human/hamster hybrids (<a href="#2" class="mim-tip-reference" title="Arfin, S. M., Cirullo, R. E., Arredondo-Vega, F. X., Smith, M. <strong>Assignment of the structural gene for asparagine synthetase to human chromosome 7.</strong> Somat. Cell Genet. 9: 517-531, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6137879/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6137879</a>] [<a href="https://doi.org/10.1007/BF01574256" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6137879">Arfin et al., 1983</a>). <a href="#7" class="mim-tip-reference" title="Lambert, M. A., Cairney, A. E. L., Ray, P. N., Weksberg, R., Andrulis, I. L. <strong>Genomic characterization of the human asparagine synthetase gene. (Abstract)</strong> Am. J. Hum. Genet. 39: A207 only, 1986."None>Lambert et al. (1986)</a> confirmed this assignment with molecular probes. Using a genomic probe, <a href="#3" class="mim-tip-reference" title="Greco, A., Ittmann, M., Barletta, C., Basilico, C., Croce, C. M., Cannizzaro, L. A., Huebner, K. <strong>Chromosomal localization of human genes required for G(1) progression in mammalian cells.</strong> Genomics 4: 240-245, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2714790/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2714790</a>] [<a href="https://doi.org/10.1016/0888-7543(89)90326-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2714790">Greco et al. (1989)</a> found that the ts11 locus is derived from the long arm of human chromosome 7, proximal to the TCRB locus (see <a href="/entry/186930">186930</a>). In situ hybridization mapped the locus more precisely to chromosome 7q21-q31. Two other members of the gene family detected by the ts11 probe were mapped to chromosomes 8pter-q24 and 21pter-q22. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6137879+2714790" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Heng, H. H. Q., Shi, X.-M., Scherer, S. W., Andrulis, I. L., Tsui, L.-C. <strong>Refined localization of the asparagine synthetase gene (ASNS) to chromosome 7, region q21.3, and characterization of the somatic cell hybrid line 4AF/106/KO15.</strong> Cytogenet. Cell Genet. 66: 135-138, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7904551/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7904551</a>] [<a href="https://doi.org/10.1159/000133685" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7904551">Heng et al. (1994)</a> refined the localization of the ASNS gene to chromosome 7q21.3 by fluorescence in situ hybridization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7904551" 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="#10" class="mim-tip-reference" title="Siu, F., Bain, P. J., LeBlanc-Chaffin, R., Chen, H., Kilberg, M. S. <strong>ATF4 is a mediator of the nutrient-sensing response pathway that activates the human asparagine synthetase gene.</strong> J. Biol. Chem. 277: 24120-24127, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11960987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11960987</a>] [<a href="https://doi.org/10.1074/jbc.M201959200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11960987">Siu et al. (2002)</a> presented evidence that ATF4 (<a href="/entry/604064">604064</a>) binds nutrient-sensing response element-1 (NSRE1) in the human ASNS gene and activates ASNS transcription in response to nutrient stress. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11960987" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In 9 patients from 4 unrelated families with asparagine synthetase deficiency (ASNSD; <a href="/entry/615574">615574</a>), <a href="#8" class="mim-tip-reference" title="Ruzzo, E. K., Capo-Chichi, J.-M., Ben-Zeev, B., Chitayat, D., Mao, H., Pappas, A. L., Hitomi, Y., Lu, Y.-F., Yao, X., Hamdan, F. F., Pelak, K., Reznik-Wolf, H., and 32 others. <strong>Deficiency of asparagine synthetase causes congenital microcephaly and a progressive form of encephalopathy.</strong> Neuron 80: 429-441, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24139043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24139043</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24139043[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.neuron.2013.08.013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24139043">Ruzzo et al. (2013)</a> identified 3 different homozygous or compound heterozygous missense mutations in the ASNS gene (<a href="#0001">108370.0001</a>-<a href="#0003">108370.0003</a>). The mutations were found by whole-exome sequencing and segregated with the disorder in all families. The phenotype was characterized by microcephaly, severely delayed psychomotor development, progressive encephalopathy, and seizure or hyperekplexic activity. Brain imaging showed cortical atrophy, enlarged ventricles, and cortical dysplasia. Affected individuals had onset in utero or at birth, and 6 died in infancy. Functional studies were not performed, but cellular studies showed that 2 of the mutant proteins were expressed at lower levels compared to wildtype and the third mutant protein was expressed at higher levels than wildtype. Two patients had decreased levels of asparagine, whereas a third had increased levels of glutamine and aspartic acid. <a href="#8" class="mim-tip-reference" title="Ruzzo, E. K., Capo-Chichi, J.-M., Ben-Zeev, B., Chitayat, D., Mao, H., Pappas, A. L., Hitomi, Y., Lu, Y.-F., Yao, X., Hamdan, F. F., Pelak, K., Reznik-Wolf, H., and 32 others. <strong>Deficiency of asparagine synthetase causes congenital microcephaly and a progressive form of encephalopathy.</strong> Neuron 80: 429-441, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24139043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24139043</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24139043[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.neuron.2013.08.013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24139043">Ruzzo et al. (2013)</a> postulated a loss-of-function effect. <a href="#8" class="mim-tip-reference" title="Ruzzo, E. K., Capo-Chichi, J.-M., Ben-Zeev, B., Chitayat, D., Mao, H., Pappas, A. L., Hitomi, Y., Lu, Y.-F., Yao, X., Hamdan, F. F., Pelak, K., Reznik-Wolf, H., and 32 others. <strong>Deficiency of asparagine synthetase causes congenital microcephaly and a progressive form of encephalopathy.</strong> Neuron 80: 429-441, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24139043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24139043</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24139043[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.neuron.2013.08.013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24139043">Ruzzo et al. (2013)</a> suggested that the brain is responsible for local de novo synthesis of asparagine, which may explain why the phenotype was neurologically restricted. Brain accumulation of aspartate and glutamate may result in increased excitability, seizure activity, and neuronal damage. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24139043" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 sisters with ASNSD from a consanguineous Indian family, <a href="#11" class="mim-tip-reference" title="Sun, J., McGillivray, A. J., Pinner, J., Yan, Z., Liu, F., Bratkovic, D., Thompson, E., Wei, X., Jiang, H., Asan, Chopra, M. <strong>Diaphragmatic eventration in sisters with asparagine synthetase deficiency: a novel homozygous ASNS mutation and expanded phenotype.</strong> JIMD Rep. 34: 1-9, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27469131/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27469131</a>] [<a href="https://doi.org/10.1007/8904_2016_3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27469131">Sun et al. (2017)</a> identified a homozygous missense mutation in the ASNS gene (R340H; <a href="#0004">108370.0004</a>). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27469131" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By whole-exome sequencing of an archived newborn blood spot, <a href="#1" class="mim-tip-reference" title="Abhyankar, A., Lamendola-Essel, M., Brennan, K., Giordano, J. L., Esteves, C., Felice, V., Wapner, R., Jobanputra, V. <strong>Clinical whole exome sequencing from dried blood spot identifies novel genetic defect underlying asparagine synthetase deficiency.</strong> Clin. Case Rep. 6: 200-205, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29375865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29375865</a>] [<a href="https://doi.org/10.1002/ccr3.1284" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29375865">Abhyankar et al. (2018)</a> identified compound heterozygous mutations in the ASNS gene (G366D, <a href="#0005">108370.0005</a>; V243A, <a href="#0006">108370.0006</a>). The infant, who died at 15 months of age without a specific diagnosis, had typical findings consistent with asparagine synthetase deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29375865" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a girl with ASNSD from a nonconsanguineous Indian family, <a href="#5" class="mim-tip-reference" title="Gupta, N., Tewari, V. V., Kumar, M., Langeh, N., Gupta, A., Mishra, P., Kaur, P., Langeh, N., Gupta, A., Mishra, P., Kaur, P., Ramprasad, V., Murugan, S., Kumar, R., Jana, M., Kabra, M. <strong>Asparagine synthetase deficiency--report of a novel mutation and review of the literature.</strong> Metab. Brain Dis. 32: 1889-1900, 2017. Note: Erratum: Metab. Brain Dis. 32: 1901 only, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28776279/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28776279</a>] [<a href="https://doi.org/10.1007/s11011-017-0073-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28776279">Gupta et al. (2017)</a> identified a homozygous missense mutation in the ASNS gene (A380S; <a href="#0007">108370.0007</a>). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28776279" 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="Sacharow, S. J., Dudenhausen, E. E., Lomelino, C. L., Rodan, L., El Achkar, C. M., Olson, H. E., Genetti, C. A., Agrawal, P. B., McKenna, R., Kilberg, M. S. <strong>Characterization of a novel variant in siblings with asparagine synthetase deficiency.</strong> Molec. Genet. Metab. 123: 317-325, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29279279/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29279279</a>] [<a href="https://doi.org/10.1016/j.ymgme.2017.12.433" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29279279">Sacharow et al. (2018)</a> identified a homozygous mutation in the ASNS gene (R49Q; <a href="#0008">108370.0008</a>) in 2 sibs, born to consanguineous Emirati parents, with ASNSD. The mutation, which was found by whole-exome sequencing, segregated with the disorder in the family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29279279" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#8" class="mim-tip-reference" title="Ruzzo, E. K., Capo-Chichi, J.-M., Ben-Zeev, B., Chitayat, D., Mao, H., Pappas, A. L., Hitomi, Y., Lu, Y.-F., Yao, X., Hamdan, F. F., Pelak, K., Reznik-Wolf, H., and 32 others. <strong>Deficiency of asparagine synthetase causes congenital microcephaly and a progressive form of encephalopathy.</strong> Neuron 80: 429-441, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24139043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24139043</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24139043[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.neuron.2013.08.013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24139043">Ruzzo et al. (2013)</a> found that homozygous mice with a hypomorphic Asns mutation (about 20% residual enzyme activity) had structural brain abnormalities, including reduced cortical thickness and enlarged ventricles. Mutant mice also showed deficits in learning and memory. Mutant mice did not show abnormal motor activity or seizure activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24139043" 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">rs398122973 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs398122973;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=rs398122973" 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=rs398122973" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In affected members of 2 Iranian Jewish families with asparagine synthetase deficiency (ASNSD; <a href="/entry/615574">615574</a>), <a href="#8" class="mim-tip-reference" title="Ruzzo, E. K., Capo-Chichi, J.-M., Ben-Zeev, B., Chitayat, D., Mao, H., Pappas, A. L., Hitomi, Y., Lu, Y.-F., Yao, X., Hamdan, F. F., Pelak, K., Reznik-Wolf, H., and 32 others. <strong>Deficiency of asparagine synthetase causes congenital microcephaly and a progressive form of encephalopathy.</strong> Neuron 80: 429-441, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24139043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24139043</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24139043[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.neuron.2013.08.013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24139043">Ruzzo et al. (2013)</a> identified a homozygous c.1084T-G transversion in the ASNS gene, resulting in a phe362-to-val (F362V) substitution at a highly conserved residue. The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. The mutation segregated with the disorder in the family and was not found in the dbSNP (build 135), 1000 Genomes Project, or Exome Sequencing Project databases or in 1,160 controls or 261 in-house exomes. It was found in 1 of 80 ancestry-matched controls, yielding a carrier frequency of 0.0125 in individuals of Iranian Jewish ancestry. Haplotype analysis indicated a founder effect. In vitro functional expression studies showed decreased amounts of mutant ASNS protein in HEK293 and COS-7 cells compared to wildtype. Glutamine and aspartic acid were increased in patients from 1 of the families. <a href="#8" class="mim-tip-reference" title="Ruzzo, E. K., Capo-Chichi, J.-M., Ben-Zeev, B., Chitayat, D., Mao, H., Pappas, A. L., Hitomi, Y., Lu, Y.-F., Yao, X., Hamdan, F. F., Pelak, K., Reznik-Wolf, H., and 32 others. <strong>Deficiency of asparagine synthetase causes congenital microcephaly and a progressive form of encephalopathy.</strong> Neuron 80: 429-441, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24139043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24139043</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24139043[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.neuron.2013.08.013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24139043">Ruzzo et al. (2013)</a> postulated a loss-of-function effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24139043" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In 3 male sibs, born of consanguineous Bangladeshi parents, with asparagine synthetase deficiency (ASNSD; <a href="/entry/615574">615574</a>), <a href="#8" class="mim-tip-reference" title="Ruzzo, E. K., Capo-Chichi, J.-M., Ben-Zeev, B., Chitayat, D., Mao, H., Pappas, A. L., Hitomi, Y., Lu, Y.-F., Yao, X., Hamdan, F. F., Pelak, K., Reznik-Wolf, H., and 32 others. <strong>Deficiency of asparagine synthetase causes congenital microcephaly and a progressive form of encephalopathy.</strong> Neuron 80: 429-441, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24139043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24139043</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24139043[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.neuron.2013.08.013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24139043">Ruzzo et al. (2013)</a> identified a homozygous c.1648C-T transition in the ASNS gene, resulting in an arg550-to-cys (R550C) substitution. Three male sibs from a French Canadian family with the disorder were found to be compound heterozygous for R550C and a c.17C-A transversion, resulting in an ala6-to-glu (A6E; <a href="#0003">108370.0003</a>) substitution. Both mutations occurred at highly conserved residues. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in both families. Neither mutation was found in the dbSNP (build 135), 1000 Genomes Project, or Exome Sequencing Project databases or in 1,160 controls, 169 in-house exomes, or 300 ancestry-matched controls. In vitro functional expression studies in HEK293 and COS-7 cells showed decreased amounts of mutant A6E protein compared to wildtype, whereas the mutant R550C protein was increased compared to wildtype. Asparagine levels were decreased in 1 patient from each family. <a href="#8" class="mim-tip-reference" title="Ruzzo, E. K., Capo-Chichi, J.-M., Ben-Zeev, B., Chitayat, D., Mao, H., Pappas, A. L., Hitomi, Y., Lu, Y.-F., Yao, X., Hamdan, F. F., Pelak, K., Reznik-Wolf, H., and 32 others. <strong>Deficiency of asparagine synthetase causes congenital microcephaly and a progressive form of encephalopathy.</strong> Neuron 80: 429-441, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24139043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24139043</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24139043[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.neuron.2013.08.013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24139043">Ruzzo et al. (2013)</a> postulated a loss-of-function effect, either by decreased amounts of ASNS protein (A6E) or decreased function (R550C). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24139043" 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> rs398122975 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs398122975;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/rs398122975?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=rs398122975" 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=rs398122975" 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=RCV000077750 OR RCV000414383" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000077750, RCV000414383" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000077750...</a>
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<p>For discussion of the ala6-to-glu (A6E) mutation in the ASNS gene that was found in compound heterozygous state in sibs with asparagine synthetase deficiency (ASNSD; <a href="/entry/615574">615574</a>) by <a href="#8" class="mim-tip-reference" title="Ruzzo, E. K., Capo-Chichi, J.-M., Ben-Zeev, B., Chitayat, D., Mao, H., Pappas, A. L., Hitomi, Y., Lu, Y.-F., Yao, X., Hamdan, F. F., Pelak, K., Reznik-Wolf, H., and 32 others. <strong>Deficiency of asparagine synthetase causes congenital microcephaly and a progressive form of encephalopathy.</strong> Neuron 80: 429-441, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24139043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24139043</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24139043[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.neuron.2013.08.013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24139043">Ruzzo et al. (2013)</a>, see <a href="#0002">108370.0002</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24139043" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 ASPARAGINE SYNTHETASE DEFICIENCY</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> rs1360484422 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1360484422;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/rs1360484422?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=rs1360484422" 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=rs1360484422" 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=RCV000787473 OR RCV001869187" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000787473, RCV001869187" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000787473...</a>
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<p>In 2 sisters, born of consanguineous Indian parents, with asparagine synthetase deficiency (ASNSD; <a href="/entry/615574">615574</a>) accompanied by diaphragmatic eventration, <a href="#11" class="mim-tip-reference" title="Sun, J., McGillivray, A. J., Pinner, J., Yan, Z., Liu, F., Bratkovic, D., Thompson, E., Wei, X., Jiang, H., Asan, Chopra, M. <strong>Diaphragmatic eventration in sisters with asparagine synthetase deficiency: a novel homozygous ASNS mutation and expanded phenotype.</strong> JIMD Rep. 34: 1-9, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27469131/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27469131</a>] [<a href="https://doi.org/10.1007/8904_2016_3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27469131">Sun et al. (2017)</a> identified a homozygous c.1019G-A transition in the ASNS gene, resulting in an arg340-to-his (R340H) substitution at a highly conserved residue in the C-terminal domain of the enzyme. The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. The parents and unaffected sibs were heterozygous for the mutation. The mutation was not found in public or internal databases. The one sister who was tested had reduced plasma asparagine levels, providing support for the diagnosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27469131" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 ASPARAGINE SYNTHETASE DEFICIENCY</strong>
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ASNS, GLY366GLU
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1584459666 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1584459666;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=rs1584459666" 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=rs1584459666" 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=RCV000787474 OR RCV004768648" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000787474, RCV004768648" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000787474...</a>
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<p>By whole-exome sequencing of an archived newborn blood spot, <a href="#1" class="mim-tip-reference" title="Abhyankar, A., Lamendola-Essel, M., Brennan, K., Giordano, J. L., Esteves, C., Felice, V., Wapner, R., Jobanputra, V. <strong>Clinical whole exome sequencing from dried blood spot identifies novel genetic defect underlying asparagine synthetase deficiency.</strong> Clin. Case Rep. 6: 200-205, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29375865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29375865</a>] [<a href="https://doi.org/10.1002/ccr3.1284" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29375865">Abhyankar et al. (2018)</a> identified an infant with compound heterozygous mutations in the ASNS gene: a c.1097G-A transition (c.1097G-A, NM_001673.4), resulting in a gly366-to-glu (G366E) substitution, and a c.728T-C transition, resulting in a val243-to-ala (V243A) substitution (<a href="#0006">108370.0006</a>). Both mutations occurred in the highly conserved asparagine synthetase domain. The mutations were confirmed by Sanger sequencing. Each parent was heterozygous for one of the mutations. The G366E variant was not present in the 1000 Genomes Project, ExAC, or UK10K databases; the V243A variant had a low minor allele frequency of 0.0002 and 0.000008 in the 1000 Genomes Project and ExAC databases, respectively, and was not seen in homozygosity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29375865" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0006" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0006 ASPARAGINE SYNTHETASE DEFICIENCY</strong>
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</span>
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</h4>
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ASNS, VAL243ALA
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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> rs148111963 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs148111963;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/rs148111963?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=rs148111963" 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=rs148111963" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000440696 OR RCV000787475" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000440696, RCV000787475" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000440696...</a>
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<p>For discussion of the c.728C-T transition (c.728C-T, NM_001673.4) in the ASNS gene, resulting in a val243-to-ala (V243A) substitution, that was found in compound heterozygous state in a patient with asparagine synthetase deficiency (ASNSD; <a href="/entry/615574">615574</a>) by <a href="#1" class="mim-tip-reference" title="Abhyankar, A., Lamendola-Essel, M., Brennan, K., Giordano, J. L., Esteves, C., Felice, V., Wapner, R., Jobanputra, V. <strong>Clinical whole exome sequencing from dried blood spot identifies novel genetic defect underlying asparagine synthetase deficiency.</strong> Clin. Case Rep. 6: 200-205, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29375865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29375865</a>] [<a href="https://doi.org/10.1002/ccr3.1284" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29375865">Abhyankar et al. (2018)</a>, see <a href="#0005">108370.0005</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29375865" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0007" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0007 ASPARAGINE SYNTHETASE DEFICIENCY</strong>
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</h4>
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ASNS, ALA380SER
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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> rs758183057 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs758183057;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/rs758183057?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=rs758183057" 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=rs758183057" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000787476 OR RCV003235394" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000787476, RCV003235394" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000787476...</a>
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<p>In a girl, born of nonconsanguineous Indian parents, with asparagine synthetase deficiency (ASNSD; <a href="/entry/615574">615574</a>), <a href="#5" class="mim-tip-reference" title="Gupta, N., Tewari, V. V., Kumar, M., Langeh, N., Gupta, A., Mishra, P., Kaur, P., Langeh, N., Gupta, A., Mishra, P., Kaur, P., Ramprasad, V., Murugan, S., Kumar, R., Jana, M., Kabra, M. <strong>Asparagine synthetase deficiency--report of a novel mutation and review of the literature.</strong> Metab. Brain Dis. 32: 1889-1900, 2017. Note: Erratum: Metab. Brain Dis. 32: 1901 only, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28776279/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28776279</a>] [<a href="https://doi.org/10.1007/s11011-017-0073-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28776279">Gupta et al. (2017)</a> identified a homozygous c.1138G-T transversion (chr7.97,483,992C-A, GRCh37) in exon 11 of the ASNS gene, resulting in an ala380-to-ser (A380S) substitution in the C-terminal asparagine synthetase domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The variant had a frequency of 0.000008313 in the ExAC database. Structural modeling suggested that the mutation affects the helix-turn-helix motif and ASNS function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28776279" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0008" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0008 ASPARAGINE SYNTHETASE DEFICIENCY</strong>
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</h4>
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ASNS, ARG49GLN
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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> rs769236847 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs769236847;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/rs769236847?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=rs769236847" 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=rs769236847" 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=RCV000432896 OR RCV000714524 OR RCV002274029" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000432896, RCV000714524, RCV002274029" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000432896...</a>
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<p>In 2 sibs, born to consanguineous Emirati parents, with asparagine synthetase deficiency (ASNSD; <a href="/entry/615574">615574</a>), <a href="#9" class="mim-tip-reference" title="Sacharow, S. J., Dudenhausen, E. E., Lomelino, C. L., Rodan, L., El Achkar, C. M., Olson, H. E., Genetti, C. A., Agrawal, P. B., McKenna, R., Kilberg, M. S. <strong>Characterization of a novel variant in siblings with asparagine synthetase deficiency.</strong> Molec. Genet. Metab. 123: 317-325, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29279279/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29279279</a>] [<a href="https://doi.org/10.1016/j.ymgme.2017.12.433" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29279279">Sacharow et al. (2018)</a> identified a homozygous c.146G-A transition (c.146G-A, NM_183356) in the ASNS gene, resulting in an arg49-to-gln (R49Q) substitution. The mutation, which was found by whole-exome sequencing, segregated with the disorder in the family. The variant has a low frequency (7.21 x 10(-6)) in the gnomAD database. Structural modeling suggested that the mutation affects the glutamine binding pocket of the protein. Studies in fibroblasts from patients showed that little to no cellular growth compared to controls in asparagine-depleted cell media, and fibroblasts from heterozygous parents showed moderate cellular growth compared to controls. The R49G variant did not appear to affect ASNS synthesis or stability. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29279279" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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Ruzzo, E. K., Capo-Chichi, J.-M., Ben-Zeev, B., Chitayat, D., Mao, H., Pappas, A. L., Hitomi, Y., Lu, Y.-F., Yao, X., Hamdan, F. F., Pelak, K., Reznik-Wolf, H., and 32 others.
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[<a href="https://doi.org/10.1016/j.neuron.2013.08.013" target="_blank">Full Text</a>]
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Sacharow, S. J., Dudenhausen, E. E., Lomelino, C. L., Rodan, L., El Achkar, C. M., Olson, H. E., Genetti, C. A., Agrawal, P. B., McKenna, R., Kilberg, M. S.
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<strong>Characterization of a novel variant in siblings with asparagine synthetase deficiency.</strong>
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Molec. Genet. Metab. 123: 317-325, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29279279/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29279279</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29279279" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.M201959200" target="_blank">Full Text</a>]
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Sun, J., McGillivray, A. J., Pinner, J., Yan, Z., Liu, F., Bratkovic, D., Thompson, E., Wei, X., Jiang, H., Asan, Chopra, M.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27469131/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27469131</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27469131" 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/10.1007/8904_2016_3" target="_blank">Full Text</a>]
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Zhang, Y. P., Lambert, M. A., Cairney, A. E. L., Wills, D., Ray, P. N., Andrulis, I. L.
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<strong>Molecular structure of the human asparagine synthetase gene.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2565875/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2565875</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2565875" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Hilary J. Vernon - updated : 05/26/2020
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Sonja A. Rasmussen - updated : 07/17/2019<br>Cassandra L. Kniffin - updated : 12/18/2013
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 6/4/1986
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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<div 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 : 05/26/2020
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 10/01/2019<br>carol : 07/18/2019<br>carol : 07/17/2019<br>carol : 05/08/2015<br>mcolton : 5/4/2015<br>carol : 12/19/2013<br>ckniffin : 12/18/2013<br>mgross : 10/7/2013<br>mgross : 4/9/2009<br>carol : 11/26/2001<br>carol : 11/25/2001<br>terry : 7/9/1998<br>jason : 7/12/1994<br>mimadm : 4/9/1994<br>supermim : 3/16/1992<br>supermim : 3/20/1990<br>supermim : 2/17/1990<br>ddp : 10/26/1989
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</span>
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</div>
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<div class="container visible-print-block">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 108370
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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ASPARAGINE SYNTHETASE; ASNS
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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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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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HUMAN COMPLEMENT FOR HAMSTER TEMPERATURE-SENSITIVE MUTANT ts11
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: ASNS</em></strong>
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 782757004;
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</span>
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</p>
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<div>
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<br />
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 7q21.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 7:97,851,677-97,928,441 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
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7q21.3
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</span>
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</td>
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<td>
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<span class="mim-font">
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Asparagine synthetase deficiency
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</span>
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</td>
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<td>
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<span class="mim-font">
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615574
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The ASNS gene encodes asparagine synthetase (EC 6.3.5.4), an enzyme that catalyzes the transfer of ammonia from glutamine to aspartic acid to form asparagine. It is expressed in most mammalian cells (summary by Zhang et al., 1989 and Ruzzo et al., 2013). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Greco et al. (1987) cloned human ASNS based on its ability to complement ts11, a temperature-sensitive (ts) mutant of the BHK hamster cell line that at the nonpermissive temperature is blocked in progression through the G1 phase of the cell growth cycle. The gene was transcribed into an mRNA of 2 kb that was expressed in all human, hamster, and mouse cell lines tested. It encodes a protein of about 550 amino acids. </p><p>Asns is highly expressed in the adult mouse brain. Ruzzo et al. (2013) found that Asns is also expressed in the developing embryonic mouse brain in the cortical plate and the ventricular and subventricular zones where neural progenitors reside. </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>Zhang et al. (1989) demonstrated that the ASNS gene spans 35 kb and contains 13 exons. The 5-prime upstream region of this gene, like other housekeeping genes, lacks conventional TATA and CAAT boxes. Both the human and the hamster genes have a high 5-prime G+C content which may play a role in expression through DNA methylation. </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>The gene for ASNS has been assigned to chromosome 7 by enzymatic analyses of human/hamster hybrids (Arfin et al., 1983). Lambert et al. (1986) confirmed this assignment with molecular probes. Using a genomic probe, Greco et al. (1989) found that the ts11 locus is derived from the long arm of human chromosome 7, proximal to the TCRB locus (see 186930). In situ hybridization mapped the locus more precisely to chromosome 7q21-q31. Two other members of the gene family detected by the ts11 probe were mapped to chromosomes 8pter-q24 and 21pter-q22. </p><p>Heng et al. (1994) refined the localization of the ASNS gene to chromosome 7q21.3 by fluorescence in situ hybridization. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Siu et al. (2002) presented evidence that ATF4 (604064) binds nutrient-sensing response element-1 (NSRE1) in the human ASNS gene and activates ASNS transcription in response to nutrient stress. </p>
|
|
</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>In 9 patients from 4 unrelated families with asparagine synthetase deficiency (ASNSD; 615574), Ruzzo et al. (2013) identified 3 different homozygous or compound heterozygous missense mutations in the ASNS gene (108370.0001-108370.0003). The mutations were found by whole-exome sequencing and segregated with the disorder in all families. The phenotype was characterized by microcephaly, severely delayed psychomotor development, progressive encephalopathy, and seizure or hyperekplexic activity. Brain imaging showed cortical atrophy, enlarged ventricles, and cortical dysplasia. Affected individuals had onset in utero or at birth, and 6 died in infancy. Functional studies were not performed, but cellular studies showed that 2 of the mutant proteins were expressed at lower levels compared to wildtype and the third mutant protein was expressed at higher levels than wildtype. Two patients had decreased levels of asparagine, whereas a third had increased levels of glutamine and aspartic acid. Ruzzo et al. (2013) postulated a loss-of-function effect. Ruzzo et al. (2013) suggested that the brain is responsible for local de novo synthesis of asparagine, which may explain why the phenotype was neurologically restricted. Brain accumulation of aspartate and glutamate may result in increased excitability, seizure activity, and neuronal damage. </p><p>In 2 sisters with ASNSD from a consanguineous Indian family, Sun et al. (2017) identified a homozygous missense mutation in the ASNS gene (R340H; 108370.0004). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. </p><p>By whole-exome sequencing of an archived newborn blood spot, Abhyankar et al. (2018) identified compound heterozygous mutations in the ASNS gene (G366D, 108370.0005; V243A, 108370.0006). The infant, who died at 15 months of age without a specific diagnosis, had typical findings consistent with asparagine synthetase deficiency. </p><p>In a girl with ASNSD from a nonconsanguineous Indian family, Gupta et al. (2017) identified a homozygous missense mutation in the ASNS gene (A380S; 108370.0007). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. </p><p>Sacharow et al. (2018) identified a homozygous mutation in the ASNS gene (R49Q; 108370.0008) in 2 sibs, born to consanguineous Emirati parents, with ASNSD. The mutation, which was found by whole-exome sequencing, segregated with the disorder in the family. </p>
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|
</span>
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<div>
|
|
<br />
|
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
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</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Ruzzo et al. (2013) found that homozygous mice with a hypomorphic Asns mutation (about 20% residual enzyme activity) had structural brain abnormalities, including reduced cortical thickness and enlarged ventricles. Mutant mice also showed deficits in learning and memory. Mutant mice did not show abnormal motor activity or seizure activity. </p>
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|
</span>
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<div>
|
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<br />
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</div>
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</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>8 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 ASPARAGINE SYNTHETASE DEFICIENCY</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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ASNS, PHE362VAL
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<br />
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|
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SNP: rs398122973,
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ClinVar: RCV000077748, RCV000812578
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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 affected members of 2 Iranian Jewish families with asparagine synthetase deficiency (ASNSD; 615574), Ruzzo et al. (2013) identified a homozygous c.1084T-G transversion in the ASNS gene, resulting in a phe362-to-val (F362V) substitution at a highly conserved residue. The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. The mutation segregated with the disorder in the family and was not found in the dbSNP (build 135), 1000 Genomes Project, or Exome Sequencing Project databases or in 1,160 controls or 261 in-house exomes. It was found in 1 of 80 ancestry-matched controls, yielding a carrier frequency of 0.0125 in individuals of Iranian Jewish ancestry. Haplotype analysis indicated a founder effect. In vitro functional expression studies showed decreased amounts of mutant ASNS protein in HEK293 and COS-7 cells compared to wildtype. Glutamine and aspartic acid were increased in patients from 1 of the families. Ruzzo et al. (2013) postulated a loss-of-function effect. </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 ASPARAGINE SYNTHETASE DEFICIENCY</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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ASNS, ARG550CYS
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<br />
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SNP: rs398122974,
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gnomAD: rs398122974,
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ClinVar: RCV000077749, RCV000201411, RCV001064729
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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 3 male sibs, born of consanguineous Bangladeshi parents, with asparagine synthetase deficiency (ASNSD; 615574), Ruzzo et al. (2013) identified a homozygous c.1648C-T transition in the ASNS gene, resulting in an arg550-to-cys (R550C) substitution. Three male sibs from a French Canadian family with the disorder were found to be compound heterozygous for R550C and a c.17C-A transversion, resulting in an ala6-to-glu (A6E; 108370.0003) substitution. Both mutations occurred at highly conserved residues. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in both families. Neither mutation was found in the dbSNP (build 135), 1000 Genomes Project, or Exome Sequencing Project databases or in 1,160 controls, 169 in-house exomes, or 300 ancestry-matched controls. In vitro functional expression studies in HEK293 and COS-7 cells showed decreased amounts of mutant A6E protein compared to wildtype, whereas the mutant R550C protein was increased compared to wildtype. Asparagine levels were decreased in 1 patient from each family. Ruzzo et al. (2013) postulated a loss-of-function effect, either by decreased amounts of ASNS protein (A6E) or decreased function (R550C). </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 ASPARAGINE SYNTHETASE DEFICIENCY</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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ASNS, ALA6GLU
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<br />
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SNP: rs398122975,
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gnomAD: rs398122975,
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ClinVar: RCV000077750, RCV000414383
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the ala6-to-glu (A6E) mutation in the ASNS gene that was found in compound heterozygous state in sibs with asparagine synthetase deficiency (ASNSD; 615574) by Ruzzo et al. (2013), see 108370.0002. </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 ASPARAGINE SYNTHETASE DEFICIENCY</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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ASNS, ARG340HIS
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<br />
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SNP: rs1360484422,
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gnomAD: rs1360484422,
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ClinVar: RCV000787473, RCV001869187
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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 2 sisters, born of consanguineous Indian parents, with asparagine synthetase deficiency (ASNSD; 615574) accompanied by diaphragmatic eventration, Sun et al. (2017) identified a homozygous c.1019G-A transition in the ASNS gene, resulting in an arg340-to-his (R340H) substitution at a highly conserved residue in the C-terminal domain of the enzyme. The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. The parents and unaffected sibs were heterozygous for the mutation. The mutation was not found in public or internal databases. The one sister who was tested had reduced plasma asparagine levels, providing support for the diagnosis. </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>.0005 ASPARAGINE SYNTHETASE DEFICIENCY</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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ASNS, GLY366GLU
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<br />
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SNP: rs1584459666,
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ClinVar: RCV000787474, RCV004768648
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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>By whole-exome sequencing of an archived newborn blood spot, Abhyankar et al. (2018) identified an infant with compound heterozygous mutations in the ASNS gene: a c.1097G-A transition (c.1097G-A, NM_001673.4), resulting in a gly366-to-glu (G366E) substitution, and a c.728T-C transition, resulting in a val243-to-ala (V243A) substitution (108370.0006). Both mutations occurred in the highly conserved asparagine synthetase domain. The mutations were confirmed by Sanger sequencing. Each parent was heterozygous for one of the mutations. The G366E variant was not present in the 1000 Genomes Project, ExAC, or UK10K databases; the V243A variant had a low minor allele frequency of 0.0002 and 0.000008 in the 1000 Genomes Project and ExAC databases, respectively, and was not seen in homozygosity. </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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<div>
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<h4>
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<span class="mim-font">
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<strong>.0006 ASPARAGINE SYNTHETASE DEFICIENCY</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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ASNS, VAL243ALA
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<br />
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SNP: rs148111963,
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gnomAD: rs148111963,
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ClinVar: RCV000440696, RCV000787475
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the c.728C-T transition (c.728C-T, NM_001673.4) in the ASNS gene, resulting in a val243-to-ala (V243A) substitution, that was found in compound heterozygous state in a patient with asparagine synthetase deficiency (ASNSD; 615574) by Abhyankar et al. (2018), see 108370.0005. </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>.0007 ASPARAGINE SYNTHETASE DEFICIENCY</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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ASNS, ALA380SER
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<br />
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SNP: rs758183057,
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gnomAD: rs758183057,
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ClinVar: RCV000787476, RCV003235394
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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 girl, born of nonconsanguineous Indian parents, with asparagine synthetase deficiency (ASNSD; 615574), Gupta et al. (2017) identified a homozygous c.1138G-T transversion (chr7.97,483,992C-A, GRCh37) in exon 11 of the ASNS gene, resulting in an ala380-to-ser (A380S) substitution in the C-terminal asparagine synthetase domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The variant had a frequency of 0.000008313 in the ExAC database. Structural modeling suggested that the mutation affects the helix-turn-helix motif and ASNS function. </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>.0008 ASPARAGINE SYNTHETASE DEFICIENCY</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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ASNS, ARG49GLN
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<br />
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SNP: rs769236847,
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gnomAD: rs769236847,
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ClinVar: RCV000432896, RCV000714524, RCV002274029
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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 2 sibs, born to consanguineous Emirati parents, with asparagine synthetase deficiency (ASNSD; 615574), Sacharow et al. (2018) identified a homozygous c.146G-A transition (c.146G-A, NM_183356) in the ASNS gene, resulting in an arg49-to-gln (R49Q) substitution. The mutation, which was found by whole-exome sequencing, segregated with the disorder in the family. The variant has a low frequency (7.21 x 10(-6)) in the gnomAD database. Structural modeling suggested that the mutation affects the glutamine binding pocket of the protein. Studies in fibroblasts from patients showed that little to no cellular growth compared to controls in asparagine-depleted cell media, and fibroblasts from heterozygous parents showed moderate cellular growth compared to controls. The R49G variant did not appear to affect ASNS synthesis or stability. </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>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Abhyankar, A., Lamendola-Essel, M., Brennan, K., Giordano, J. L., Esteves, C., Felice, V., Wapner, R., Jobanputra, V.
|
|
<strong>Clinical whole exome sequencing from dried blood spot identifies novel genetic defect underlying asparagine synthetase deficiency.</strong>
|
|
Clin. Case Rep. 6: 200-205, 2018.
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[PubMed: 29375865]
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[Full Text: https://doi.org/10.1002/ccr3.1284]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Arfin, S. M., Cirullo, R. E., Arredondo-Vega, F. X., Smith, M.
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<strong>Assignment of the structural gene for asparagine synthetase to human chromosome 7.</strong>
|
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Somat. Cell Genet. 9: 517-531, 1983.
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[PubMed: 6137879]
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[Full Text: https://doi.org/10.1007/BF01574256]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Greco, A., Ittmann, M., Barletta, C., Basilico, C., Croce, C. M., Cannizzaro, L. A., Huebner, K.
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|
<strong>Chromosomal localization of human genes required for G(1) progression in mammalian cells.</strong>
|
|
Genomics 4: 240-245, 1989.
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[PubMed: 2714790]
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[Full Text: https://doi.org/10.1016/0888-7543(89)90326-1]
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</p>
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<li>
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<p class="mim-text-font">
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Greco, A., Ittmann, M., Basilico, C.
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<strong>Molecular cloning of a gene that is necessary for G(1) progression in mammalian cells.</strong>
|
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Proc. Nat. Acad. Sci. 84: 1565-1569, 1987.
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[PubMed: 3470743]
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[Full Text: https://doi.org/10.1073/pnas.84.6.1565]
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</p>
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<li>
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<p class="mim-text-font">
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Gupta, N., Tewari, V. V., Kumar, M., Langeh, N., Gupta, A., Mishra, P., Kaur, P., Langeh, N., Gupta, A., Mishra, P., Kaur, P., Ramprasad, V., Murugan, S., Kumar, R., Jana, M., Kabra, M.
|
|
<strong>Asparagine synthetase deficiency--report of a novel mutation and review of the literature.</strong>
|
|
Metab. Brain Dis. 32: 1889-1900, 2017. Note: Erratum: Metab. Brain Dis. 32: 1901 only, 2017.
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[PubMed: 28776279]
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[Full Text: https://doi.org/10.1007/s11011-017-0073-6]
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</p>
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<li>
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<p class="mim-text-font">
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Heng, H. H. Q., Shi, X.-M., Scherer, S. W., Andrulis, I. L., Tsui, L.-C.
|
|
<strong>Refined localization of the asparagine synthetase gene (ASNS) to chromosome 7, region q21.3, and characterization of the somatic cell hybrid line 4AF/106/KO15.</strong>
|
|
Cytogenet. Cell Genet. 66: 135-138, 1994.
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[PubMed: 7904551]
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[Full Text: https://doi.org/10.1159/000133685]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Lambert, M. A., Cairney, A. E. L., Ray, P. N., Weksberg, R., Andrulis, I. L.
|
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<strong>Genomic characterization of the human asparagine synthetase gene. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 39: A207 only, 1986.
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Ruzzo, E. K., Capo-Chichi, J.-M., Ben-Zeev, B., Chitayat, D., Mao, H., Pappas, A. L., Hitomi, Y., Lu, Y.-F., Yao, X., Hamdan, F. F., Pelak, K., Reznik-Wolf, H., and 32 others.
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<strong>Deficiency of asparagine synthetase causes congenital microcephaly and a progressive form of encephalopathy.</strong>
|
|
Neuron 80: 429-441, 2013.
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[PubMed: 24139043]
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[Full Text: https://doi.org/10.1016/j.neuron.2013.08.013]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Sacharow, S. J., Dudenhausen, E. E., Lomelino, C. L., Rodan, L., El Achkar, C. M., Olson, H. E., Genetti, C. A., Agrawal, P. B., McKenna, R., Kilberg, M. S.
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<strong>Characterization of a novel variant in siblings with asparagine synthetase deficiency.</strong>
|
|
Molec. Genet. Metab. 123: 317-325, 2018.
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[PubMed: 29279279]
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[Full Text: https://doi.org/10.1016/j.ymgme.2017.12.433]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Siu, F., Bain, P. J., LeBlanc-Chaffin, R., Chen, H., Kilberg, M. S.
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<strong>ATF4 is a mediator of the nutrient-sensing response pathway that activates the human asparagine synthetase gene.</strong>
|
|
J. Biol. Chem. 277: 24120-24127, 2002.
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[PubMed: 11960987]
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[Full Text: https://doi.org/10.1074/jbc.M201959200]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Sun, J., McGillivray, A. J., Pinner, J., Yan, Z., Liu, F., Bratkovic, D., Thompson, E., Wei, X., Jiang, H., Asan, Chopra, M.
|
|
<strong>Diaphragmatic eventration in sisters with asparagine synthetase deficiency: a novel homozygous ASNS mutation and expanded phenotype.</strong>
|
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JIMD Rep. 34: 1-9, 2017.
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[PubMed: 27469131]
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[Full Text: https://doi.org/10.1007/8904_2016_3]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Zhang, Y. P., Lambert, M. A., Cairney, A. E. L., Wills, D., Ray, P. N., Andrulis, I. L.
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<strong>Molecular structure of the human asparagine synthetase gene.</strong>
|
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Genomics 4: 259-265, 1989.
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[PubMed: 2565875]
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[Full Text: https://doi.org/10.1016/0888-7543(89)90329-7]
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</p>
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</li>
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</ol>
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Contributors:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Hilary J. Vernon - updated : 05/26/2020<br>Sonja A. Rasmussen - updated : 07/17/2019<br>Cassandra L. Kniffin - updated : 12/18/2013
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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 : 6/4/1986
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carol : 05/26/2020<br>carol : 10/01/2019<br>carol : 07/18/2019<br>carol : 07/17/2019<br>carol : 05/08/2015<br>mcolton : 5/4/2015<br>carol : 12/19/2013<br>ckniffin : 12/18/2013<br>mgross : 10/7/2013<br>mgross : 4/9/2009<br>carol : 11/26/2001<br>carol : 11/25/2001<br>terry : 7/9/1998<br>jason : 7/12/1994<br>mimadm : 4/9/1994<br>supermim : 3/16/1992<br>supermim : 3/20/1990<br>supermim : 2/17/1990<br>ddp : 10/26/1989
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