3277 lines
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Entry
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- *604402 - ST3 BETA-GALACTOSIDE ALPHA-2,3-SIALYLTRANSFERASE 5; ST3GAL5
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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">*604402</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/604402">Table View</a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000115525;t=ENST00000638572" 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=8869" 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=604402" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000115525;t=ENST00000638572" 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_001042437,NM_001354223,NM_001354224,NM_001354226,NM_001354227,NM_001354229,NM_001354233,NM_001354234,NM_001354238,NM_001354247,NM_001354248,NM_001363847,NM_003896,XM_047446237,XM_047446238,XM_047446239,XM_047446240,XM_047446241,XR_007084231,XR_007084237" 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_003896" 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=604402" 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=05098&isoform_id=05098_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/ST3GAL5" 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/3779139,4262430,6841206,7670071,34530764,37183327,62988760,94958325,109633044,109633046,114325459,119619880,119619881,119619882,119619883,119619884,119619885,119619886,189047140,193785528,221040684,221045298,957950542,957950545,1229385524,1229385560,1229385622,1229385666,1237937880,1237937904,1237938199,1241781232,1241781258,1241781353,1394533344,2217331850,2217331852,2217331854,2217331856,2217331858,2462578206,2462578208,2462578210,2462578212,2462578214" 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/Q9UNP4" 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=8869" 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=ENSG00000115525;t=ENST00000638572" 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=ST3GAL5" 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=ST3GAL5" 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+8869" 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/ST3GAL5" 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:8869" 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/8869" 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=chr2&hgg_gene=ENST00000638572.2&hgg_start=85837120&hgg_end=85889034&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:10872" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:10872" 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/st3gal5" 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=604402[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=604402[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/ST3GAL5/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/ENSG00000115525" 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=ST3GAL5" 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=ST3GAL5" 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=ST3GAL5" 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=ST3GAL5&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/PA35773" 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:10872" 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://www.mousephenotype.org/data/genes/MGI:1339963" 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/ST3GAL5#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:1339963" 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/8869/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=8869" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-060322-1" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:8869" 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=ST3GAL5&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> 722762005<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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604402
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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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ST3 BETA-GALACTOSIDE ALPHA-2,3-SIALYLTRANSFERASE 5; ST3GAL5
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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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SIALYLTRANSFERASE 9; SIAT9<br />
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CMP-NeuAc:LACTOSYLCERAMIDE ALPHA-2,3-SIALYLTRANSFERASE<br />
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ALPHA-2,3-SIALYLTRANSFERASE V; ST3GALV<br />
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GM3 SYNTHASE<br />
|
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SATI
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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=ST3GAL5" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">ST3GAL5</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/2/435?start=-3&limit=10&highlight=435">2p11.2</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr2:85837120-85889034&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'})">2:85,837,120-85,889,034</a> </span>
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</em>
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</strong>
|
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</div>
|
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<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
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<tr class="active">
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<th>
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Location
|
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</th>
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<th>
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Phenotype
|
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
|
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</th>
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<th>
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Phenotype <br /> mapping key
|
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</th>
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</tr>
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</thead>
|
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<tbody>
|
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|
<tr>
|
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<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/2/435?start=-3&limit=10&highlight=435">
|
|
2p11.2
|
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</a>
|
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</span>
|
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</td>
|
|
|
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<td>
|
|
<span class="mim-font">
|
|
Salt and pepper developmental regression syndrome
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<a href="/entry/609056"> 609056 </a>
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
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|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
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<p>The ST3GAL5 gene encodes a sialyltransferase that synthesizes ganglioside GM3 synthase (<a href="https://enzyme.expasy.org/EC/2.4.99.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 2.4.99.9</a>), a glycosphingolipid enriched in neural tissue, by adding sialic acid to lactosylceramide (summary by <a href="#2" class="mim-tip-reference" title="Boccuto, L., Aoki, K., Flanagan-Steet, H., Chen, C.-F., Fan, X., Bartel, F., Petukh, M., Pittman, A., Saul, R., Chaubey, A., Alexov, E., Tiemeyer, M., Steet, R., Schwartz, C. E. <strong>A mutation in a ganglioside biosynthetic enzyme, ST3GAL5, results in salt & pepper syndrome, a neurocutaneous disorder with altered glycolipid and glycoprotein glycosylation.</strong> Hum. Molec. Genet. 23: 418-433, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24026681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24026681</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24026681[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddt434" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24026681">Boccuto et al., 2014</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24026681" 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>Sialic acid-containing glycosphingolipids, or gangliosides, have various important biologic functions. In vertebrates, almost all the ganglio-series gangliosides are synthesized from a common precursor, ganglioside GM3, which has the simplest structure among the major gangliosides. GM3, a plasma membrane glycosphingolipid, participates in induction of differentiation, modulation of proliferation, maintenance of fibroblast morphology, signal transduction, and integrin-mediated cell adhesion. ST3GAL5 is responsible for the synthesis of GM3 (<a href="#4" class="mim-tip-reference" title="Ishii, A., Ohta, M., Watanabe, Y., Matsuda, K., Ishiyama, K., Sakoe, K., Nakamura, M., Inokuchi, J., Sanai, Y., Saito, M. <strong>Expression cloning and functional characterization of human cDNA for ganglioside GM3 synthase.</strong> J. Biol. Chem. 273: 31652-31655, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9822625/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9822625</a>] [<a href="https://doi.org/10.1074/jbc.273.48.31652" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9822625">Ishii et al., 1998</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9822625" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using a cDNA library prepared from a monocyte-differentiated human myelogenous leukemia cell line, <a href="#4" class="mim-tip-reference" title="Ishii, A., Ohta, M., Watanabe, Y., Matsuda, K., Ishiyama, K., Sakoe, K., Nakamura, M., Inokuchi, J., Sanai, Y., Saito, M. <strong>Expression cloning and functional characterization of human cDNA for ganglioside GM3 synthase.</strong> J. Biol. Chem. 273: 31652-31655, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9822625/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9822625</a>] [<a href="https://doi.org/10.1074/jbc.273.48.31652" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9822625">Ishii et al. (1998)</a> isolated a cDNA encoding SIAT9, which they called GM3 synthase, by a modified expression cloning strategy. The predicted 362-amino acid SIAT9 protein has features characteristic of the sialyltransferase family, including a type II transmembrane topology and the sialyl motifs L in the center and S in the C-terminal region. However, SIAT9 contains the nonconservative substitution of asp to his at a position in sialyl motif L that is invariant in all other known sialyltransferases. Hydropathy plot analysis suggested that SIAT9 may by anchored to the luminal side of the Golgi membrane. SIAT9 shares approximately 27 to 41% amino acid sequence similarity with other known sialyltransferases that catalyze formation of the alpha-2,3 and alpha-2,6 linkages of sialic acid to the acceptor galactose moiety, but not with enzymes that catalyze formation of the alpha-2,8 linkage to the nonreducing terminal sialic acid residue of glycosphingolipids and glycoproteins. Northern blot analysis detected a major 2.4-kb SIAT9 transcript in all tissues tested, with highest expression in brain, skeletal muscle, placenta, and testis. SIAT9 was widely distributed in human brain, with slightly elevated expression in the cerebral cortex, temporal lobe, and putamen. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9822625" 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 screening a fetal brain cDNA library, followed by 5-prime RACE, <a href="#5" class="mim-tip-reference" title="Kim, K.-W., Kim, S.-W., Min, K.-S., Kim, C.-H., Lee, Y.-C. <strong>Genomic structure of human GM3 synthase gene (hST3Gal V) and identification of mRNA isoforms in the 5-prime-untranslated region.</strong> Gene 273: 163-171, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11595162/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11595162</a>] [<a href="https://doi.org/10.1016/s0378-1119(01)00595-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11595162">Kim et al. (2001)</a> identified 4 ST3GAL5 variants that differed only in the 5-prime UTR. The variants resulted from a combination of alternative splicing and alternative promoter utilization. Northern blot analysis of adult and fetal tissue detected a 2.4-kb transcript expressed at highest levels in fetal brain and lung and in adult brain, placenta, and skeletal muscle. Lower expression was detected in fetal kidney. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11595162" 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="Ishii, A., Ohta, M., Watanabe, Y., Matsuda, K., Ishiyama, K., Sakoe, K., Nakamura, M., Inokuchi, J., Sanai, Y., Saito, M. <strong>Expression cloning and functional characterization of human cDNA for ganglioside GM3 synthase.</strong> J. Biol. Chem. 273: 31652-31655, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9822625/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9822625</a>] [<a href="https://doi.org/10.1074/jbc.273.48.31652" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9822625">Ishii et al. (1998)</a> determined that the substrate specificity of SIAT9 was highly restricted to lactosylceramide as the acceptor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9822625" 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="#5" class="mim-tip-reference" title="Kim, K.-W., Kim, S.-W., Min, K.-S., Kim, C.-H., Lee, Y.-C. <strong>Genomic structure of human GM3 synthase gene (hST3Gal V) and identification of mRNA isoforms in the 5-prime-untranslated region.</strong> Gene 273: 163-171, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11595162/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11595162</a>] [<a href="https://doi.org/10.1016/s0378-1119(01)00595-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11595162">Kim et al. (2001)</a> determined that the ST3GAL5 gene contains 9 exons and spans about 44 kb. The coding region is located in exons 4 to 9. <a href="#6" class="mim-tip-reference" title="Kim, S.-W., Lee, S.-H., Kim, K.-S., Kim, C.-H., Choo, Y.-K., Lee, Y.-C. <strong>Isolation and characterization of the promoter region of the human GM3 synthase gene.</strong> Biochim. Biophys. Acta 1578: 84-89, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12393190/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12393190</a>] [<a href="https://doi.org/10.1016/s0167-4781(02)00505-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12393190">Kim et al. (2002)</a> determined that the 5-prime flanking region of the ST3GAL5 gene lacks canonical TATA and CAAT boxes, but contains several putative transcription factor-binding sites, with both positive and negative regulatory elements. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11595162+12393190" 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 genomic sequence analysis, <a href="#13" class="mim-tip-reference" title="Zeng, G., Gao, L., Xia, T., Tencomnao, T., Yu, R. K. <strong>Characterization of the 5-prime-flanking fragment of the human GM3-synthase gene.</strong> Biochim. Biophys. Acta 1625: 30-35, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12527423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12527423</a>] [<a href="https://doi.org/10.1016/s0167-4781(02)00573-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12527423">Zeng et al. (2003)</a> determined that the SIAT9 gene contains 7 exons and spans more than 62 kb. They noted that the SIAT9 introns were larger in their analysis than those reported by <a href="#5" class="mim-tip-reference" title="Kim, K.-W., Kim, S.-W., Min, K.-S., Kim, C.-H., Lee, Y.-C. <strong>Genomic structure of human GM3 synthase gene (hST3Gal V) and identification of mRNA isoforms in the 5-prime-untranslated region.</strong> Gene 273: 163-171, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11595162/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11595162</a>] [<a href="https://doi.org/10.1016/s0378-1119(01)00595-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11595162">Kim et al. (2001)</a>. <a href="#13" class="mim-tip-reference" title="Zeng, G., Gao, L., Xia, T., Tencomnao, T., Yu, R. K. <strong>Characterization of the 5-prime-flanking fragment of the human GM3-synthase gene.</strong> Biochim. Biophys. Acta 1625: 30-35, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12527423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12527423</a>] [<a href="https://doi.org/10.1016/s0167-4781(02)00573-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12527423">Zeng et al. (2003)</a> identified 2 transcription start sites upstream of exon 1. A 5-prime proximal fragment bound several transcription factors in a DNA-binding assay. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12527423+11595162" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By genomic sequence analysis, <a href="#5" class="mim-tip-reference" title="Kim, K.-W., Kim, S.-W., Min, K.-S., Kim, C.-H., Lee, Y.-C. <strong>Genomic structure of human GM3 synthase gene (hST3Gal V) and identification of mRNA isoforms in the 5-prime-untranslated region.</strong> Gene 273: 163-171, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11595162/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11595162</a>] [<a href="https://doi.org/10.1016/s0378-1119(01)00595-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11595162">Kim et al. (2001)</a> mapped the SIAT9 gene to chromosome 2. <a href="#13" class="mim-tip-reference" title="Zeng, G., Gao, L., Xia, T., Tencomnao, T., Yu, R. K. <strong>Characterization of the 5-prime-flanking fragment of the human GM3-synthase gene.</strong> Biochim. Biophys. Acta 1625: 30-35, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12527423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12527423</a>] [<a href="https://doi.org/10.1016/s0167-4781(02)00573-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12527423">Zeng et al. (2003)</a> mapped the SAIT9 gene to chromosome 2p24.3-p24.1 by genomic sequence analysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12527423+11595162" 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="Simpson, M. A., Cross, H., Proukakis, C., Priestman, D. A., Neville, D. C. A., Reinkensmeier, G., Wang, H., Wiznitzer, M., Gurtz, K., Verganelaki, A., Pryde, A., Patton, M. A., Dwek, R. A., Butters, T. D., Platt, F. M., Crosby, A. H. <strong>Infantile-onset symptomatic epilepsy syndrome caused by a homozygous loss-of-function mutation of GM3 synthase.</strong> Nature Genet. 36: 1225-1229, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15502825/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15502825</a>] [<a href="https://doi.org/10.1038/ng1460" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15502825">Simpson et al. (2004)</a> mapped an infantile-onset symptomatic epilepsy syndrome (<a href="/entry/609056">609056</a>) to 2p12-p11.2 by identification of a region of homozygosity and found a nonsense mutation in the SIAT9 gene, which was located in that region. Thus, the location of the gene appeared to be more proximal than had been thought. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15502825" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a large Old Order Amish pedigree in Geauga County, Ohio, <a href="#9" class="mim-tip-reference" title="Simpson, M. A., Cross, H., Proukakis, C., Priestman, D. A., Neville, D. C. A., Reinkensmeier, G., Wang, H., Wiznitzer, M., Gurtz, K., Verganelaki, A., Pryde, A., Patton, M. A., Dwek, R. A., Butters, T. D., Platt, F. M., Crosby, A. H. <strong>Infantile-onset symptomatic epilepsy syndrome caused by a homozygous loss-of-function mutation of GM3 synthase.</strong> Nature Genet. 36: 1225-1229, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15502825/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15502825</a>] [<a href="https://doi.org/10.1038/ng1460" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15502825">Simpson et al. (2004)</a> identified an autosomal recessive infantile-onset epilepsy syndrome associated with developmental stagnation and blindness (SPDRS; <a href="/entry/609056">609056</a>). They sequenced genes in a region of homozygosity on 2p12-p11.2 and identified a nonsense mutation in SIAT9 (R288X; <a href="#0001">604402.0001</a>) that was predicted to result in a premature termination of the GM3 synthase enzyme (also called lactosylceramide alpha-2,3 sialyltransferase). GM3 synthase catalyzes the initial step in the biosynthesis of most complex gangliosides from lactosylceramide. Biochemical analysis of plasma glycosphingolipids confirmed that affected individuals lacked GM3 synthase activity, as marked by a complete lack of GM3 ganglioside and its biosynthetic derivatives and an increase in lactosylceramide and its alternative derivatives. Although the relationship between defects in ganglioside catabolism and a range of lysosomal storage diseases is well documented, this was, it seems, the first report of a disruption of ganglioside biosynthesis associated with human disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15502825" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 sibs, born of consanguineous French parents, with refractory epilepsy and delayed psychomotor development, <a href="#3" class="mim-tip-reference" title="Fragaki, K., Ait-El-Mkadem, S., Chaussenot, A., Gire, C., Mengual, R., Bonesso, L., Beneteau, M., Ricci, J.-E., Desquiret-Dumas, V., Procaccio, V., Rotig, A., Paquis-Flucklinger, V. <strong>Refractory epilepsy and mitochondrial dysfunction due to GM3 synthase deficiency.</strong> Europ. J. Hum. Genet. 21: 528-534, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22990144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22990144</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22990144[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2012.202" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22990144">Fragaki et al. (2013)</a> identified a homozygous truncating mutation in the SIAT9 gene (<a href="#0001">604402.0001</a>), which was the same mutation identified by <a href="#9" class="mim-tip-reference" title="Simpson, M. A., Cross, H., Proukakis, C., Priestman, D. A., Neville, D. C. A., Reinkensmeier, G., Wang, H., Wiznitzer, M., Gurtz, K., Verganelaki, A., Pryde, A., Patton, M. A., Dwek, R. A., Butters, T. D., Platt, F. M., Crosby, A. H. <strong>Infantile-onset symptomatic epilepsy syndrome caused by a homozygous loss-of-function mutation of GM3 synthase.</strong> Nature Genet. 36: 1225-1229, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15502825/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15502825</a>] [<a href="https://doi.org/10.1038/ng1460" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15502825">Simpson et al. (2004)</a> in Amish patients with a similar disorder. The mutation, which was identified by exome sequencing, segregated with the disorder in the family. Mass spectrometry analysis of patient fibroblasts showed complete absence of GM3 ganglioside and its biosynthetic derivatives and an upregulation of the alternative globoside pathway. Fibroblasts also showed a decrease in mitochondrial membrane potential, consistent with secondary dysfunction of the respiratory chain, as well as increased apoptosis. <a href="#3" class="mim-tip-reference" title="Fragaki, K., Ait-El-Mkadem, S., Chaussenot, A., Gire, C., Mengual, R., Bonesso, L., Beneteau, M., Ricci, J.-E., Desquiret-Dumas, V., Procaccio, V., Rotig, A., Paquis-Flucklinger, V. <strong>Refractory epilepsy and mitochondrial dysfunction due to GM3 synthase deficiency.</strong> Europ. J. Hum. Genet. 21: 528-534, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22990144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22990144</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22990144[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2012.202" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22990144">Fragaki et al. (2013)</a> suggested that the accumulation of globosides may have had a role in the respiratory chain dysfunction. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=22990144+15502825" 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="#8" class="mim-tip-reference" title="Saul, R. A., Wilkes, G., Stevenson, R. E. <strong>'Salt-and-pepper' pigmentary changes with severe mental retardation: a new neurocutaneous syndrome?</strong> Proc. Greenwood Genet. Center 2: 6-9, 1983."None>Saul et al. (1983)</a> reported sibs from an African American family with pigmentary disturbances, which they described as 'salt and pepper' pigmentary changes, and severe mental retardation. <a href="#2" class="mim-tip-reference" title="Boccuto, L., Aoki, K., Flanagan-Steet, H., Chen, C.-F., Fan, X., Bartel, F., Petukh, M., Pittman, A., Saul, R., Chaubey, A., Alexov, E., Tiemeyer, M., Steet, R., Schwartz, C. E. <strong>A mutation in a ganglioside biosynthetic enzyme, ST3GAL5, results in salt & pepper syndrome, a neurocutaneous disorder with altered glycolipid and glycoprotein glycosylation.</strong> Hum. Molec. Genet. 23: 418-433, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24026681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24026681</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24026681[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddt434" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24026681">Boccuto et al. (2014)</a> detected a homozygous mutation in the ST3GAL5 gene in affected family members (<a href="#0002">604402.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24026681" 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>Gangliosides are present on all mammalian plasma membranes, where they participate in recognition and signaling activities. <a href="#11" class="mim-tip-reference" title="Yamashita, T., Hashiramoto, A., Haluzik, M., Mizukami, H., Beck, S., Norton, A., Kono, M., Tsuji, S., Daniotti, J. L., Werth, N., Sandhoff, R., Sandhoff, K., Proia, R. L. <strong>Enhanced insulin sensitivity in mice lacking ganglioside GM3.</strong> Proc. Nat. Acad. Sci. 100: 3445-3449, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12629211/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12629211</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12629211[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0635898100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12629211">Yamashita et al. (2003)</a> generated mice lacking GM3 synthase which were unable to synthesize GM3 ganglioside. The mutant mice were viable and appeared to be without major abnormalities, but showed a heightened sensitivity to insulin, the basis of which was found to be enhanced insulin receptor phosphorylation in skeletal muscle. Importantly, the mutant mice were protected from high-fat diet-induced insulin resistance. The results showed that GM3 ganglioside is a negative regulator of insulin signaling, making it a potential therapeutic target in type II diabetes (<a href="/entry/125853">125853</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12629211" 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="#12" class="mim-tip-reference" title="Yoshikawa, M., Go, S., Takasaki, K., Kakazu, Y., Ohashi, M., Nagafuku, M., Kabayama, K., Sekimoto, J., Suzuki, S., Takaiwa, K., Kimitsuki, T., Matsumoto, N., Komune, S., Kamei, D., Saito, M., Fujiwara, M., Iwasaki, K., Inokuchi, J. <strong>Mice lacking ganglioside GM3 synthase exhibit complete hearing loss due to selective degeneration of the organ of Corti.</strong> Proc. Nat. Acad. Sci. 106: 9483-9488, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19470479/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19470479</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19470479[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0903279106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19470479">Yoshikawa et al. (2009)</a> found that Sati -/- mice exhibited no startle reflex in response to various acoustic stimulations, yet they demonstrated normal startle responses to air puffs. Electrophysiologic and histologic analyses of Sati -/- mice revealed that the organ of Corti in the inner ear was selectively degenerated and the spiral ganglion was scattered, but all other regions of the cochlea appeared normal. Scanning electron microscopy showed a significant deficit in hair bundles of outer hair cells, but not inner hair cells, in the organ of Corti of Sati -/- mice. Examination of brainstem auditory-evoked potentials revealed attenuated auditory responses in Sati -/- mice at postnatal day 14 (P14), when auditory responses were first observed in wildtype mice. No auditory responses were detected in Sati -/- mice by P17. Thin-layer chromatography revealed dramatic changes in several gangliosides during development in wildtype cochlea. At P13, GM3 was expressed in all regions of the cochlea, but at P14 and in adult mice, GM3 expression was limited to stria vascularis, spiral ganglion, and the organ of Corti. No GM3 was detected in the cochlea of Sati -/- mice. <a href="#12" class="mim-tip-reference" title="Yoshikawa, M., Go, S., Takasaki, K., Kakazu, Y., Ohashi, M., Nagafuku, M., Kabayama, K., Sekimoto, J., Suzuki, S., Takaiwa, K., Kimitsuki, T., Matsumoto, N., Komune, S., Kamei, D., Saito, M., Fujiwara, M., Iwasaki, K., Inokuchi, J. <strong>Mice lacking ganglioside GM3 synthase exhibit complete hearing loss due to selective degeneration of the organ of Corti.</strong> Proc. Nat. Acad. Sci. 106: 9483-9488, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19470479/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19470479</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19470479[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0903279106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19470479">Yoshikawa et al. (2009)</a> concluded that SATI-mediated synthesis of GM3 in the cochlea is essential for acquisition and maintenance of hearing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19470479" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Bharathi, S. S., Zhang, B. B., Paul, E., Zhang, Y., Schmidt, A. V., Fowler, B., Wu, Y., Tiemeyer, M., Inamori, K. I., Inokuchi, J. I., Goetzman, E. S. <strong>GM3 synthase deficiency increases brain glucose metabolism in mice.</strong> Molec. Genet. Metab. 137: 342-348, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36335793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36335793</a>] [<a href="https://doi.org/10.1016/j.ymgme.2022.10.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="36335793">Bharathi et al. (2022)</a> demonstrated that, compared to wildtype mice, Gm3 synthase knockout mice (Gm3s -/-) had increased whole-body energy expenditure as evidenced by increased oxygen consumption and carbon dioxide production and a higher respiratory exchange rate, indicative of increased reliance on glucose for energy. PET scanning also demonstrated that the Gm3s -/- mice had greater brain glucose uptake compared to wildtype mice after short fasting. Complex I respiration and ADP-stimulated state 3 mitochondrial respiration was increased in brain homogenates from Gm3s -/- mice, which was attributed to increased expression of pyruvate dehydrogenase deficiency. Inhibition of glycolysis resulted in a decrease in kainate-induced seizures in the mutant mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36335793" 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 affected Amish individuals with autosomal recessive salt and pepper developmental regression syndrome (SPDRS; <a href="/entry/609056">609056</a>), <a href="#9" class="mim-tip-reference" title="Simpson, M. A., Cross, H., Proukakis, C., Priestman, D. A., Neville, D. C. A., Reinkensmeier, G., Wang, H., Wiznitzer, M., Gurtz, K., Verganelaki, A., Pryde, A., Patton, M. A., Dwek, R. A., Butters, T. D., Platt, F. M., Crosby, A. H. <strong>Infantile-onset symptomatic epilepsy syndrome caused by a homozygous loss-of-function mutation of GM3 synthase.</strong> Nature Genet. 36: 1225-1229, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15502825/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15502825</a>] [<a href="https://doi.org/10.1038/ng1460" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15502825">Simpson et al. (2004)</a> demonstrated homozygosity for a c.694C-T transition in the SIAT9 gene, resulting in an arg232-to-ter (R232X) substitution. Heterozygosity was found in several carriers. The mutation was predicted to cause a loss of function of GM3 synthase. Affected children completely lacked GM3 and its downstream biosynthetic derivatives but they had increased levels of the immediate precursor to GM3, lactosylceramide, and evidence of increased flux through the globoside and paragloboside pathways. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15502825" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Wang, H., Wang, A., Wang, D., Bright, A., Sency, V., Zhou, A., Xin, B. <strong>Early growth and development impairments in patients with ganglioside GM3 synthase deficiency.</strong> Clin. Genet. 89: 625-629, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26649472/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26649472</a>] [<a href="https://doi.org/10.1111/cge.12703" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26649472">Wang et al. (2016)</a> reported 37 Amish patients, including 8 previously reported by <a href="#9" class="mim-tip-reference" title="Simpson, M. A., Cross, H., Proukakis, C., Priestman, D. A., Neville, D. C. A., Reinkensmeier, G., Wang, H., Wiznitzer, M., Gurtz, K., Verganelaki, A., Pryde, A., Patton, M. A., Dwek, R. A., Butters, T. D., Platt, F. M., Crosby, A. H. <strong>Infantile-onset symptomatic epilepsy syndrome caused by a homozygous loss-of-function mutation of GM3 synthase.</strong> Nature Genet. 36: 1225-1229, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15502825/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15502825</a>] [<a href="https://doi.org/10.1038/ng1460" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15502825">Simpson et al. (2004)</a>, who were homozygous for the R288X mutation in exon 6 of the ST3GAL5 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15502825+26649472" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 sibs, born of consanguineous French parents, with refractory epilepsy and delayed psychomotor development, <a href="#3" class="mim-tip-reference" title="Fragaki, K., Ait-El-Mkadem, S., Chaussenot, A., Gire, C., Mengual, R., Bonesso, L., Beneteau, M., Ricci, J.-E., Desquiret-Dumas, V., Procaccio, V., Rotig, A., Paquis-Flucklinger, V. <strong>Refractory epilepsy and mitochondrial dysfunction due to GM3 synthase deficiency.</strong> Europ. J. Hum. Genet. 21: 528-534, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22990144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22990144</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22990144[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2012.202" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22990144">Fragaki et al. (2013)</a> identified a homozygous c.862C-T transition in exon 6 of the ST3GAL5 gene, resulting in an arg288-to-ter (R288X) substitution. The mutation was the same as that identified by <a href="#9" class="mim-tip-reference" title="Simpson, M. A., Cross, H., Proukakis, C., Priestman, D. A., Neville, D. C. A., Reinkensmeier, G., Wang, H., Wiznitzer, M., Gurtz, K., Verganelaki, A., Pryde, A., Patton, M. A., Dwek, R. A., Butters, T. D., Platt, F. M., Crosby, A. H. <strong>Infantile-onset symptomatic epilepsy syndrome caused by a homozygous loss-of-function mutation of GM3 synthase.</strong> Nature Genet. 36: 1225-1229, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15502825/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15502825</a>] [<a href="https://doi.org/10.1038/ng1460" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15502825">Simpson et al. (2004)</a> in Amish patients with a similar disorder; the numbering by <a href="#3" class="mim-tip-reference" title="Fragaki, K., Ait-El-Mkadem, S., Chaussenot, A., Gire, C., Mengual, R., Bonesso, L., Beneteau, M., Ricci, J.-E., Desquiret-Dumas, V., Procaccio, V., Rotig, A., Paquis-Flucklinger, V. <strong>Refractory epilepsy and mitochondrial dysfunction due to GM3 synthase deficiency.</strong> Europ. J. Hum. Genet. 21: 528-534, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22990144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22990144</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22990144[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2012.202" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22990144">Fragaki et al. (2013)</a> was based on a later reference sequence. The mutation was identified by exome sequencing and segregated with the disorder in the family. Mass spectrometry analysis of patient fibroblasts showed complete absence of GM3 ganglioside and its biosynthetic derivatives and an upregulation of the alternative globoside pathway. Fibroblasts also showed a decrease in mitochondrial membrane potential, consistent with secondary dysfunction of the respiratory chain, as well as increased apoptosis. <a href="#3" class="mim-tip-reference" title="Fragaki, K., Ait-El-Mkadem, S., Chaussenot, A., Gire, C., Mengual, R., Bonesso, L., Beneteau, M., Ricci, J.-E., Desquiret-Dumas, V., Procaccio, V., Rotig, A., Paquis-Flucklinger, V. <strong>Refractory epilepsy and mitochondrial dysfunction due to GM3 synthase deficiency.</strong> Europ. J. Hum. Genet. 21: 528-534, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22990144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22990144</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22990144[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2012.202" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22990144">Fragaki et al. (2013)</a> suggested that the accumulation of globosides may have had a role in the respiratory chain dysfunction. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=22990144+15502825" 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>.0002 SALT AND PEPPER DEVELOPMENTAL REGRESSION SYNDROME</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs534438354 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs534438354;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/rs534438354?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=rs534438354" 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=rs534438354" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 2 sibs originally reported by <a href="#8" class="mim-tip-reference" title="Saul, R. A., Wilkes, G., Stevenson, R. E. <strong>'Salt-and-pepper' pigmentary changes with severe mental retardation: a new neurocutaneous syndrome?</strong> Proc. Greenwood Genet. Center 2: 6-9, 1983."None>Saul et al. (1983)</a> as having 'salt and pepper' mental retardation syndrome (SPDRS; <a href="/entry/609056">609056</a>), <a href="#2" class="mim-tip-reference" title="Boccuto, L., Aoki, K., Flanagan-Steet, H., Chen, C.-F., Fan, X., Bartel, F., Petukh, M., Pittman, A., Saul, R., Chaubey, A., Alexov, E., Tiemeyer, M., Steet, R., Schwartz, C. E. <strong>A mutation in a ganglioside biosynthetic enzyme, ST3GAL5, results in salt & pepper syndrome, a neurocutaneous disorder with altered glycolipid and glycoprotein glycosylation.</strong> Hum. Molec. Genet. 23: 418-433, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24026681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24026681</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24026681[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddt434" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24026681">Boccuto et al. (2014)</a> identified a homozygous c.994G-A transition in exon 7 of the ST3GAL5 gene, resulting in a glu332-to-lys (E332K) substitution in the S-motif of the protein. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the dbSNP (build 137) database or in 561 individuals from South Carolina, the geographic region of the family. Molecular modeling studies suggested that the E332K substitution would destabilize the protein. Patient fibroblasts showed no GM2 or GM3, consistent with a loss of ST3GAL5 function. Analysis of the glycolipid profile in patient cells and plasma showed a shift toward ceramides with longer fatty acid chain length. Microarray analysis of glycosyltransferase mRNAs detected modestly increased expression of ST3GAL5 as well as greater changes in transcripts encoding enzymes that lie downstream of ST3GAL5 and in other glycosphingolipid biosynthetic pathways. Comprehensive glycomic analysis of N-linked, O-linked, and glycosphingolipid glycans revealed collateral modulation of glycoprotein sialylation in response to the loss of complex gangliosides. Morpholino knockdown of st3gal5 in zebrafish embryos caused increased neuronal cell death that could be rescued by expression of the wildtype gene. The findings indicated that human neural cells are extremely sensitive to ST3GAL5 deficiency and altered glycosphingolipid synthesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24026681" 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> rs886037930 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs886037930;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/rs886037930?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=rs886037930" 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=rs886037930" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 2 Korean sisters with salt and pepper developmental regression syndrome (SPDRS; <a href="/entry/609056">609056</a>), <a href="#7" class="mim-tip-reference" title="Lee, J. S., Yoo, Y., Lim, B. C., Kim, K. J., Song, J., Choi, M., Chae, J.-H. <strong>GM3 synthase deficiency due to ST3GAL5 variants in two Korean female siblings: masquerading as Rett syndrome-like phenotype.</strong> Am. J. Med. Genet. 170A: 2200-2205, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27232954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27232954</a>] [<a href="https://doi.org/10.1002/ajmg.a.37773" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27232954">Lee et al. (2016)</a> identified compound heterozygous missense mutations in the ST3GAL5 gene: a c.584G-C transversion (c.584G-C, NM_003896), resulting in a cys195-to-ser (C195S) substitution, and a c.601G-A transition, resulting in a gly201-to-arg (G201R; <a href="#0004">604402.0004</a>) substitution. The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The C195S variant was not found in the 1000 Genomes Project or ExAC databases, whereas the G201R variant was found at a low frequency (8.3 x 10(-6)). Both mutations occurred at highly conserved residues in the L-motif of the protein. Plasma gangliosides in the 2 sibs were barely detectable, suggesting a loss of function. Functional studies of the variants and measurement of enzyme activity in patient cell were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27232954" 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 SALT AND PEPPER DEVELOPMENTAL REGRESSION SYNDROME</strong>
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<p>For discussion of the c.601G-A transition (c.601G-A, NM_003896) in the ST3GAL5 gene, resulting in a gly201-to-arg (G201R) substitution, that was found in compound heterozygous state in 2 sibs with salt and pepper developmental regression syndrome (SPDRS; <a href="/entry/609056">609056</a>) by <a href="#7" class="mim-tip-reference" title="Lee, J. S., Yoo, Y., Lim, B. C., Kim, K. J., Song, J., Choi, M., Chae, J.-H. <strong>GM3 synthase deficiency due to ST3GAL5 variants in two Korean female siblings: masquerading as Rett syndrome-like phenotype.</strong> Am. J. Med. Genet. 170A: 2200-2205, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27232954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27232954</a>] [<a href="https://doi.org/10.1002/ajmg.a.37773" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27232954">Lee et al. (2016)</a>, see <a href="#0003">604402.0003</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27232954" 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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Bharathi, S. S., Zhang, B. B., Paul, E., Zhang, Y., Schmidt, A. V., Fowler, B., Wu, Y., Tiemeyer, M., Inamori, K. I., Inokuchi, J. I., Goetzman, E. S.
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<strong>GM3 synthase deficiency increases brain glucose metabolism in mice.</strong>
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Molec. Genet. Metab. 137: 342-348, 2022.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36335793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36335793</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36335793" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ymgme.2022.10.006" target="_blank">Full Text</a>]
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<a id="Boccuto2014" class="mim-anchor"></a>
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Boccuto, L., Aoki, K., Flanagan-Steet, H., Chen, C.-F., Fan, X., Bartel, F., Petukh, M., Pittman, A., Saul, R., Chaubey, A., Alexov, E., Tiemeyer, M., Steet, R., Schwartz, C. E.
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<strong>A mutation in a ganglioside biosynthetic enzyme, ST3GAL5, results in salt & pepper syndrome, a neurocutaneous disorder with altered glycolipid and glycoprotein glycosylation.</strong>
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Hum. Molec. Genet. 23: 418-433, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24026681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24026681</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24026681[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24026681" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddt434" target="_blank">Full Text</a>]
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<a id="Fragaki2013" class="mim-anchor"></a>
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Fragaki, K., Ait-El-Mkadem, S., Chaussenot, A., Gire, C., Mengual, R., Bonesso, L., Beneteau, M., Ricci, J.-E., Desquiret-Dumas, V., Procaccio, V., Rotig, A., Paquis-Flucklinger, V.
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<strong>Refractory epilepsy and mitochondrial dysfunction due to GM3 synthase deficiency.</strong>
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Europ. J. Hum. Genet. 21: 528-534, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22990144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22990144</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22990144[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22990144" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ejhg.2012.202" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9822625/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9822625</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9822625" 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.273.48.31652" target="_blank">Full Text</a>]
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Kim, K.-W., Kim, S.-W., Min, K.-S., Kim, C.-H., Lee, Y.-C.
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<strong>Genomic structure of human GM3 synthase gene (hST3Gal V) and identification of mRNA isoforms in the 5-prime-untranslated region.</strong>
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Gene 273: 163-171, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11595162/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11595162</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11595162" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0378-1119(01)00595-9" target="_blank">Full Text</a>]
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Kim, S.-W., Lee, S.-H., Kim, K.-S., Kim, C.-H., Choo, Y.-K., Lee, Y.-C.
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<strong>Isolation and characterization of the promoter region of the human GM3 synthase gene.</strong>
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Biochim. Biophys. Acta 1578: 84-89, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12393190/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12393190</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12393190" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0167-4781(02)00505-5" target="_blank">Full Text</a>]
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<a id="Lee2016" class="mim-anchor"></a>
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Lee, J. S., Yoo, Y., Lim, B. C., Kim, K. J., Song, J., Choi, M., Chae, J.-H.
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<strong>GM3 synthase deficiency due to ST3GAL5 variants in two Korean female siblings: masquerading as Rett syndrome-like phenotype.</strong>
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Am. J. Med. Genet. 170A: 2200-2205, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27232954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27232954</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27232954" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.37773" target="_blank">Full Text</a>]
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<a id="Saul1983" class="mim-anchor"></a>
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Saul, R. A., Wilkes, G., Stevenson, R. E.
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<strong>'Salt-and-pepper' pigmentary changes with severe mental retardation: a new neurocutaneous syndrome?</strong>
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Simpson, M. A., Cross, H., Proukakis, C., Priestman, D. A., Neville, D. C. A., Reinkensmeier, G., Wang, H., Wiznitzer, M., Gurtz, K., Verganelaki, A., Pryde, A., Patton, M. A., Dwek, R. A., Butters, T. D., Platt, F. M., Crosby, A. H.
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<strong>Infantile-onset symptomatic epilepsy syndrome caused by a homozygous loss-of-function mutation of GM3 synthase.</strong>
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Nature Genet. 36: 1225-1229, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15502825/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15502825</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15502825" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng1460" target="_blank">Full Text</a>]
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Wang, H., Wang, A., Wang, D., Bright, A., Sency, V., Zhou, A., Xin, B.
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<strong>Early growth and development impairments in patients with ganglioside GM3 synthase deficiency.</strong>
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Clin. Genet. 89: 625-629, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26649472/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26649472</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26649472" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/cge.12703" target="_blank">Full Text</a>]
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Yamashita, T., Hashiramoto, A., Haluzik, M., Mizukami, H., Beck, S., Norton, A., Kono, M., Tsuji, S., Daniotti, J. L., Werth, N., Sandhoff, R., Sandhoff, K., Proia, R. L.
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<strong>Enhanced insulin sensitivity in mice lacking ganglioside GM3.</strong>
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Proc. Nat. Acad. Sci. 100: 3445-3449, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12629211/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12629211</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12629211[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12629211" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.0635898100" target="_blank">Full Text</a>]
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Yoshikawa, M., Go, S., Takasaki, K., Kakazu, Y., Ohashi, M., Nagafuku, M., Kabayama, K., Sekimoto, J., Suzuki, S., Takaiwa, K., Kimitsuki, T., Matsumoto, N., Komune, S., Kamei, D., Saito, M., Fujiwara, M., Iwasaki, K., Inokuchi, J.
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<strong>Mice lacking ganglioside GM3 synthase exhibit complete hearing loss due to selective degeneration of the organ of Corti.</strong>
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Proc. Nat. Acad. Sci. 106: 9483-9488, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19470479/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19470479</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19470479[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19470479" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.0903279106" target="_blank">Full Text</a>]
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Zeng, G., Gao, L., Xia, T., Tencomnao, T., Yu, R. K.
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<strong>Characterization of the 5-prime-flanking fragment of the human GM3-synthase gene.</strong>
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Biochim. Biophys. Acta 1625: 30-35, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12527423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12527423</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12527423" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0167-4781(02)00573-0" target="_blank">Full Text</a>]
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Hilary J. Vernon - updated : 02/09/2023
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Carol A. Bocchini - updated : 02/28/2017<br>Cassandra L. Kniffin - updated : 09/12/2016<br>Cassandra L. Kniffin - updated : 7/15/2014<br>Cassandra L. Kniffin - updated : 5/13/2013<br>Patricia A. Hartz - updated : 12/2/2010<br>Victor A. McKusick - updated : 11/19/2004<br>Victor A. McKusick - updated : 4/25/2003
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carol : 02/09/2023<br>carol : 05/13/2020<br>carol : 02/28/2017<br>carol : 09/16/2016<br>ckniffin : 09/12/2016<br>alopez : 07/21/2014<br>mcolton : 7/16/2014<br>ckniffin : 7/15/2014<br>carol : 5/20/2013<br>ckniffin : 5/13/2013<br>mgross : 12/2/2010<br>terry : 12/2/2010<br>terry : 7/26/2006<br>mgross : 5/22/2006<br>mgross : 5/1/2006<br>mgross : 4/28/2006<br>mgross : 4/28/2006<br>alopez : 11/30/2004<br>terry : 11/19/2004<br>mgross : 11/9/2004<br>terry : 11/5/2004<br>tkritzer : 5/6/2003<br>terry : 4/25/2003<br>mgross : 8/22/2002<br>mgross : 1/5/2000<br>psherman : 1/5/2000
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 604402
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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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ST3 BETA-GALACTOSIDE ALPHA-2,3-SIALYLTRANSFERASE 5; ST3GAL5
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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SIALYLTRANSFERASE 9; SIAT9<br />
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CMP-NeuAc:LACTOSYLCERAMIDE ALPHA-2,3-SIALYLTRANSFERASE<br />
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ALPHA-2,3-SIALYLTRANSFERASE V; ST3GALV<br />
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GM3 SYNTHASE<br />
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SATI
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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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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: ST3GAL5</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> 722762005;
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</span>
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</p>
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<div>
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 2p11.2
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Genomic coordinates <span class="small">(GRCh38)</span> : 2:85,837,120-85,889,034 </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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<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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2p11.2
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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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Salt and pepper developmental regression syndrome
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</span>
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</td>
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<td>
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<span class="mim-font">
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609056
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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 ST3GAL5 gene encodes a sialyltransferase that synthesizes ganglioside GM3 synthase (EC 2.4.99.9), a glycosphingolipid enriched in neural tissue, by adding sialic acid to lactosylceramide (summary by Boccuto et al., 2014). </p><p>Sialic acid-containing glycosphingolipids, or gangliosides, have various important biologic functions. In vertebrates, almost all the ganglio-series gangliosides are synthesized from a common precursor, ganglioside GM3, which has the simplest structure among the major gangliosides. GM3, a plasma membrane glycosphingolipid, participates in induction of differentiation, modulation of proliferation, maintenance of fibroblast morphology, signal transduction, and integrin-mediated cell adhesion. ST3GAL5 is responsible for the synthesis of GM3 (Ishii et al., 1998). </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>Using a cDNA library prepared from a monocyte-differentiated human myelogenous leukemia cell line, Ishii et al. (1998) isolated a cDNA encoding SIAT9, which they called GM3 synthase, by a modified expression cloning strategy. The predicted 362-amino acid SIAT9 protein has features characteristic of the sialyltransferase family, including a type II transmembrane topology and the sialyl motifs L in the center and S in the C-terminal region. However, SIAT9 contains the nonconservative substitution of asp to his at a position in sialyl motif L that is invariant in all other known sialyltransferases. Hydropathy plot analysis suggested that SIAT9 may by anchored to the luminal side of the Golgi membrane. SIAT9 shares approximately 27 to 41% amino acid sequence similarity with other known sialyltransferases that catalyze formation of the alpha-2,3 and alpha-2,6 linkages of sialic acid to the acceptor galactose moiety, but not with enzymes that catalyze formation of the alpha-2,8 linkage to the nonreducing terminal sialic acid residue of glycosphingolipids and glycoproteins. Northern blot analysis detected a major 2.4-kb SIAT9 transcript in all tissues tested, with highest expression in brain, skeletal muscle, placenta, and testis. SIAT9 was widely distributed in human brain, with slightly elevated expression in the cerebral cortex, temporal lobe, and putamen. </p><p>By screening a fetal brain cDNA library, followed by 5-prime RACE, Kim et al. (2001) identified 4 ST3GAL5 variants that differed only in the 5-prime UTR. The variants resulted from a combination of alternative splicing and alternative promoter utilization. Northern blot analysis of adult and fetal tissue detected a 2.4-kb transcript expressed at highest levels in fetal brain and lung and in adult brain, placenta, and skeletal muscle. Lower expression was detected in fetal kidney. </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>Ishii et al. (1998) determined that the substrate specificity of SIAT9 was highly restricted to lactosylceramide as the acceptor. </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>Kim et al. (2001) determined that the ST3GAL5 gene contains 9 exons and spans about 44 kb. The coding region is located in exons 4 to 9. Kim et al. (2002) determined that the 5-prime flanking region of the ST3GAL5 gene lacks canonical TATA and CAAT boxes, but contains several putative transcription factor-binding sites, with both positive and negative regulatory elements. </p><p>By genomic sequence analysis, Zeng et al. (2003) determined that the SIAT9 gene contains 7 exons and spans more than 62 kb. They noted that the SIAT9 introns were larger in their analysis than those reported by Kim et al. (2001). Zeng et al. (2003) identified 2 transcription start sites upstream of exon 1. A 5-prime proximal fragment bound several transcription factors in a DNA-binding assay. </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>By genomic sequence analysis, Kim et al. (2001) mapped the SIAT9 gene to chromosome 2. Zeng et al. (2003) mapped the SAIT9 gene to chromosome 2p24.3-p24.1 by genomic sequence analysis. </p><p>Simpson et al. (2004) mapped an infantile-onset symptomatic epilepsy syndrome (609056) to 2p12-p11.2 by identification of a region of homozygosity and found a nonsense mutation in the SIAT9 gene, which was located in that region. Thus, the location of the gene appeared to be more proximal than had been thought. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In a large Old Order Amish pedigree in Geauga County, Ohio, Simpson et al. (2004) identified an autosomal recessive infantile-onset epilepsy syndrome associated with developmental stagnation and blindness (SPDRS; 609056). They sequenced genes in a region of homozygosity on 2p12-p11.2 and identified a nonsense mutation in SIAT9 (R288X; 604402.0001) that was predicted to result in a premature termination of the GM3 synthase enzyme (also called lactosylceramide alpha-2,3 sialyltransferase). GM3 synthase catalyzes the initial step in the biosynthesis of most complex gangliosides from lactosylceramide. Biochemical analysis of plasma glycosphingolipids confirmed that affected individuals lacked GM3 synthase activity, as marked by a complete lack of GM3 ganglioside and its biosynthetic derivatives and an increase in lactosylceramide and its alternative derivatives. Although the relationship between defects in ganglioside catabolism and a range of lysosomal storage diseases is well documented, this was, it seems, the first report of a disruption of ganglioside biosynthesis associated with human disease. </p><p>In 2 sibs, born of consanguineous French parents, with refractory epilepsy and delayed psychomotor development, Fragaki et al. (2013) identified a homozygous truncating mutation in the SIAT9 gene (604402.0001), which was the same mutation identified by Simpson et al. (2004) in Amish patients with a similar disorder. The mutation, which was identified by exome sequencing, segregated with the disorder in the family. Mass spectrometry analysis of patient fibroblasts showed complete absence of GM3 ganglioside and its biosynthetic derivatives and an upregulation of the alternative globoside pathway. Fibroblasts also showed a decrease in mitochondrial membrane potential, consistent with secondary dysfunction of the respiratory chain, as well as increased apoptosis. Fragaki et al. (2013) suggested that the accumulation of globosides may have had a role in the respiratory chain dysfunction. </p><p>Saul et al. (1983) reported sibs from an African American family with pigmentary disturbances, which they described as 'salt and pepper' pigmentary changes, and severe mental retardation. Boccuto et al. (2014) detected a homozygous mutation in the ST3GAL5 gene in affected family members (604402.0002). </p>
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</span>
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<div>
|
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
|
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<p>Gangliosides are present on all mammalian plasma membranes, where they participate in recognition and signaling activities. Yamashita et al. (2003) generated mice lacking GM3 synthase which were unable to synthesize GM3 ganglioside. The mutant mice were viable and appeared to be without major abnormalities, but showed a heightened sensitivity to insulin, the basis of which was found to be enhanced insulin receptor phosphorylation in skeletal muscle. Importantly, the mutant mice were protected from high-fat diet-induced insulin resistance. The results showed that GM3 ganglioside is a negative regulator of insulin signaling, making it a potential therapeutic target in type II diabetes (125853). </p><p>Yoshikawa et al. (2009) found that Sati -/- mice exhibited no startle reflex in response to various acoustic stimulations, yet they demonstrated normal startle responses to air puffs. Electrophysiologic and histologic analyses of Sati -/- mice revealed that the organ of Corti in the inner ear was selectively degenerated and the spiral ganglion was scattered, but all other regions of the cochlea appeared normal. Scanning electron microscopy showed a significant deficit in hair bundles of outer hair cells, but not inner hair cells, in the organ of Corti of Sati -/- mice. Examination of brainstem auditory-evoked potentials revealed attenuated auditory responses in Sati -/- mice at postnatal day 14 (P14), when auditory responses were first observed in wildtype mice. No auditory responses were detected in Sati -/- mice by P17. Thin-layer chromatography revealed dramatic changes in several gangliosides during development in wildtype cochlea. At P13, GM3 was expressed in all regions of the cochlea, but at P14 and in adult mice, GM3 expression was limited to stria vascularis, spiral ganglion, and the organ of Corti. No GM3 was detected in the cochlea of Sati -/- mice. Yoshikawa et al. (2009) concluded that SATI-mediated synthesis of GM3 in the cochlea is essential for acquisition and maintenance of hearing. </p><p>Bharathi et al. (2022) demonstrated that, compared to wildtype mice, Gm3 synthase knockout mice (Gm3s -/-) had increased whole-body energy expenditure as evidenced by increased oxygen consumption and carbon dioxide production and a higher respiratory exchange rate, indicative of increased reliance on glucose for energy. PET scanning also demonstrated that the Gm3s -/- mice had greater brain glucose uptake compared to wildtype mice after short fasting. Complex I respiration and ADP-stimulated state 3 mitochondrial respiration was increased in brain homogenates from Gm3s -/- mice, which was attributed to increased expression of pyruvate dehydrogenase deficiency. Inhibition of glycolysis resulted in a decrease in kainate-induced seizures in the mutant mice. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>ALLELIC VARIANTS</strong>
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</span>
|
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<strong>4 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0001 SALT AND PEPPER DEVELOPMENTAL REGRESSION SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ST3GAL5, ARG288TER
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<br />
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SNP: rs104893668,
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gnomAD: rs104893668,
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ClinVar: RCV000005895, RCV001553145, RCV003904809
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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 affected Amish individuals with autosomal recessive salt and pepper developmental regression syndrome (SPDRS; 609056), Simpson et al. (2004) demonstrated homozygosity for a c.694C-T transition in the SIAT9 gene, resulting in an arg232-to-ter (R232X) substitution. Heterozygosity was found in several carriers. The mutation was predicted to cause a loss of function of GM3 synthase. Affected children completely lacked GM3 and its downstream biosynthetic derivatives but they had increased levels of the immediate precursor to GM3, lactosylceramide, and evidence of increased flux through the globoside and paragloboside pathways. </p><p>Wang et al. (2016) reported 37 Amish patients, including 8 previously reported by Simpson et al. (2004), who were homozygous for the R288X mutation in exon 6 of the ST3GAL5 gene. </p><p>In 2 sibs, born of consanguineous French parents, with refractory epilepsy and delayed psychomotor development, Fragaki et al. (2013) identified a homozygous c.862C-T transition in exon 6 of the ST3GAL5 gene, resulting in an arg288-to-ter (R288X) substitution. The mutation was the same as that identified by Simpson et al. (2004) in Amish patients with a similar disorder; the numbering by Fragaki et al. (2013) was based on a later reference sequence. The mutation was identified by exome sequencing and segregated with the disorder in the family. Mass spectrometry analysis of patient fibroblasts showed complete absence of GM3 ganglioside and its biosynthetic derivatives and an upregulation of the alternative globoside pathway. Fibroblasts also showed a decrease in mitochondrial membrane potential, consistent with secondary dysfunction of the respiratory chain, as well as increased apoptosis. Fragaki et al. (2013) suggested that the accumulation of globosides may have had a role in the respiratory chain dysfunction. </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 SALT AND PEPPER DEVELOPMENTAL REGRESSION SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ST3GAL5, GLU332LYS
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<br />
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SNP: rs534438354,
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gnomAD: rs534438354,
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ClinVar: RCV000128792, RCV003151747
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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 originally reported by Saul et al. (1983) as having 'salt and pepper' mental retardation syndrome (SPDRS; 609056), Boccuto et al. (2014) identified a homozygous c.994G-A transition in exon 7 of the ST3GAL5 gene, resulting in a glu332-to-lys (E332K) substitution in the S-motif of the protein. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the dbSNP (build 137) database or in 561 individuals from South Carolina, the geographic region of the family. Molecular modeling studies suggested that the E332K substitution would destabilize the protein. Patient fibroblasts showed no GM2 or GM3, consistent with a loss of ST3GAL5 function. Analysis of the glycolipid profile in patient cells and plasma showed a shift toward ceramides with longer fatty acid chain length. Microarray analysis of glycosyltransferase mRNAs detected modestly increased expression of ST3GAL5 as well as greater changes in transcripts encoding enzymes that lie downstream of ST3GAL5 and in other glycosphingolipid biosynthetic pathways. Comprehensive glycomic analysis of N-linked, O-linked, and glycosphingolipid glycans revealed collateral modulation of glycoprotein sialylation in response to the loss of complex gangliosides. Morpholino knockdown of st3gal5 in zebrafish embryos caused increased neuronal cell death that could be rescued by expression of the wildtype gene. The findings indicated that human neural cells are extremely sensitive to ST3GAL5 deficiency and altered glycosphingolipid synthesis. </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 SALT AND PEPPER DEVELOPMENTAL REGRESSION SYNDROME</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ST3GAL5, CYS195SER
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<br />
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SNP: rs886037930,
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gnomAD: rs886037930,
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ClinVar: RCV000240853
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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 Korean sisters with salt and pepper developmental regression syndrome (SPDRS; 609056), Lee et al. (2016) identified compound heterozygous missense mutations in the ST3GAL5 gene: a c.584G-C transversion (c.584G-C, NM_003896), resulting in a cys195-to-ser (C195S) substitution, and a c.601G-A transition, resulting in a gly201-to-arg (G201R; 604402.0004) substitution. The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The C195S variant was not found in the 1000 Genomes Project or ExAC databases, whereas the G201R variant was found at a low frequency (8.3 x 10(-6)). Both mutations occurred at highly conserved residues in the L-motif of the protein. Plasma gangliosides in the 2 sibs were barely detectable, suggesting a loss of function. Functional studies of the variants and measurement of enzyme activity in patient cell were not performed. </p>
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<span class="mim-font">
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<strong>.0004 SALT AND PEPPER DEVELOPMENTAL REGRESSION SYNDROME</strong>
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ST3GAL5, GLY201ARG
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<br />
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SNP: rs771732955,
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gnomAD: rs771732955,
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ClinVar: RCV000240856
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<p>For discussion of the c.601G-A transition (c.601G-A, NM_003896) in the ST3GAL5 gene, resulting in a gly201-to-arg (G201R) substitution, that was found in compound heterozygous state in 2 sibs with salt and pepper developmental regression syndrome (SPDRS; 609056) by Lee et al. (2016), see 604402.0003. </p>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<ol>
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<li>
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Bharathi, S. S., Zhang, B. B., Paul, E., Zhang, Y., Schmidt, A. V., Fowler, B., Wu, Y., Tiemeyer, M., Inamori, K. I., Inokuchi, J. I., Goetzman, E. S.
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<strong>GM3 synthase deficiency increases brain glucose metabolism in mice.</strong>
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Molec. Genet. Metab. 137: 342-348, 2022.
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[PubMed: 36335793]
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[Full Text: https://doi.org/10.1016/j.ymgme.2022.10.006]
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Boccuto, L., Aoki, K., Flanagan-Steet, H., Chen, C.-F., Fan, X., Bartel, F., Petukh, M., Pittman, A., Saul, R., Chaubey, A., Alexov, E., Tiemeyer, M., Steet, R., Schwartz, C. E.
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<strong>A mutation in a ganglioside biosynthetic enzyme, ST3GAL5, results in salt & pepper syndrome, a neurocutaneous disorder with altered glycolipid and glycoprotein glycosylation.</strong>
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Hum. Molec. Genet. 23: 418-433, 2014.
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Fragaki, K., Ait-El-Mkadem, S., Chaussenot, A., Gire, C., Mengual, R., Bonesso, L., Beneteau, M., Ricci, J.-E., Desquiret-Dumas, V., Procaccio, V., Rotig, A., Paquis-Flucklinger, V.
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<strong>Refractory epilepsy and mitochondrial dysfunction due to GM3 synthase deficiency.</strong>
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Europ. J. Hum. Genet. 21: 528-534, 2013.
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Ishii, A., Ohta, M., Watanabe, Y., Matsuda, K., Ishiyama, K., Sakoe, K., Nakamura, M., Inokuchi, J., Sanai, Y., Saito, M.
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Kim, K.-W., Kim, S.-W., Min, K.-S., Kim, C.-H., Lee, Y.-C.
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<strong>Genomic structure of human GM3 synthase gene (hST3Gal V) and identification of mRNA isoforms in the 5-prime-untranslated region.</strong>
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Gene 273: 163-171, 2001.
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Kim, S.-W., Lee, S.-H., Kim, K.-S., Kim, C.-H., Choo, Y.-K., Lee, Y.-C.
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<strong>Isolation and characterization of the promoter region of the human GM3 synthase gene.</strong>
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Biochim. Biophys. Acta 1578: 84-89, 2002.
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<p class="mim-text-font">
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Lee, J. S., Yoo, Y., Lim, B. C., Kim, K. J., Song, J., Choi, M., Chae, J.-H.
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<strong>GM3 synthase deficiency due to ST3GAL5 variants in two Korean female siblings: masquerading as Rett syndrome-like phenotype.</strong>
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Am. J. Med. Genet. 170A: 2200-2205, 2016.
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Saul, R. A., Wilkes, G., Stevenson, R. E.
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<strong>'Salt-and-pepper' pigmentary changes with severe mental retardation: a new neurocutaneous syndrome?</strong>
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Proc. Greenwood Genet. Center 2: 6-9, 1983.
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Simpson, M. A., Cross, H., Proukakis, C., Priestman, D. A., Neville, D. C. A., Reinkensmeier, G., Wang, H., Wiznitzer, M., Gurtz, K., Verganelaki, A., Pryde, A., Patton, M. A., Dwek, R. A., Butters, T. D., Platt, F. M., Crosby, A. H.
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<strong>Infantile-onset symptomatic epilepsy syndrome caused by a homozygous loss-of-function mutation of GM3 synthase.</strong>
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Nature Genet. 36: 1225-1229, 2004.
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[PubMed: 15502825]
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Wang, H., Wang, A., Wang, D., Bright, A., Sency, V., Zhou, A., Xin, B.
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<strong>Early growth and development impairments in patients with ganglioside GM3 synthase deficiency.</strong>
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Clin. Genet. 89: 625-629, 2016.
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[PubMed: 26649472]
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[Full Text: https://doi.org/10.1111/cge.12703]
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Yamashita, T., Hashiramoto, A., Haluzik, M., Mizukami, H., Beck, S., Norton, A., Kono, M., Tsuji, S., Daniotti, J. L., Werth, N., Sandhoff, R., Sandhoff, K., Proia, R. L.
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<strong>Enhanced insulin sensitivity in mice lacking ganglioside GM3.</strong>
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Proc. Nat. Acad. Sci. 100: 3445-3449, 2003.
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Yoshikawa, M., Go, S., Takasaki, K., Kakazu, Y., Ohashi, M., Nagafuku, M., Kabayama, K., Sekimoto, J., Suzuki, S., Takaiwa, K., Kimitsuki, T., Matsumoto, N., Komune, S., Kamei, D., Saito, M., Fujiwara, M., Iwasaki, K., Inokuchi, J.
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<strong>Mice lacking ganglioside GM3 synthase exhibit complete hearing loss due to selective degeneration of the organ of Corti.</strong>
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Proc. Nat. Acad. Sci. 106: 9483-9488, 2009.
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[PubMed: 19470479]
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[Full Text: https://doi.org/10.1073/pnas.0903279106]
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<li>
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<p class="mim-text-font">
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Zeng, G., Gao, L., Xia, T., Tencomnao, T., Yu, R. K.
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<strong>Characterization of the 5-prime-flanking fragment of the human GM3-synthase gene.</strong>
|
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Biochim. Biophys. Acta 1625: 30-35, 2003.
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[PubMed: 12527423]
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[Full Text: https://doi.org/10.1016/s0167-4781(02)00573-0]
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Hilary J. Vernon - updated : 02/09/2023<br>Carol A. Bocchini - updated : 02/28/2017<br>Cassandra L. Kniffin - updated : 09/12/2016<br>Cassandra L. Kniffin - updated : 7/15/2014<br>Cassandra L. Kniffin - updated : 5/13/2013<br>Patricia A. Hartz - updated : 12/2/2010<br>Victor A. McKusick - updated : 11/19/2004<br>Victor A. McKusick - updated : 4/25/2003
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