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Entry
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- *605460 - ATP-BINDING CASSETTE, SUBFAMILY G, MEMBER 8; ABCG8
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- OMIM
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<p>
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<span class="h4">*605460</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</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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<a href="#biochemicalFeatures">Biochemical Features</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/605460">Table View</a>
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<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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<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 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=ENSG00000143921;t=ENST00000272286" 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=64241" 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=605460" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</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=ENSG00000143921;t=ENST00000272286" 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_001357321,NM_022437" 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_022437" 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=605460" 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=05679&isoform_id=05679_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/ABCG8" 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/11692802,11967971,15088540,15146444,15150316,15150320,17432916,62988623,109731355,119620690,219519465,1269361809" 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/Q9H221" 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=64241" 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=ENSG00000143921;t=ENST00000272286" 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=ABCG8" 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=ABCG8" 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+64241" 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/ABCG8" 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:64241" 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/64241" 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=ENST00000272286.4&hgg_start=43838971&hgg_end=43882988&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:13887" 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:13887" 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/abcg8" 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=605460[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=605460[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/ABCG8/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/ENSG00000143921" 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=ABCG8" 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=ABCG8" 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=ABCG8" 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=ABCG8&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/PA24412" 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:13887" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0051121.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1914720" 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/ABCG8#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:1914720" 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/64241/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=64241" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00006522;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-050517-41" 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:64241" 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=ABCG8&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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</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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605460
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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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ATP-BINDING CASSETTE, SUBFAMILY G, MEMBER 8; ABCG8
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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">
|
|
STEROLIN 2
|
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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=ABCG8" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">ABCG8</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/2/219?start=-3&limit=10&highlight=219">2p21</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr2:43838971-43882988&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'})">2:43,838,971-43,882,988</a> </span>
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</em>
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
|
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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>
|
|
Phenotype
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|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=611465,210250" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
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</a>
|
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</span>
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</th>
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<th>
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|
Phenotype <br /> MIM number
|
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</th>
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<th>
|
|
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>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/2/219?start=-3&limit=10&highlight=219">
|
|
2p21
|
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</a>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
{Gallbladder disease 4}
|
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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/611465"> 611465 </a>
|
|
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
</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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|
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</tr>
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<tr>
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<td>
|
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<span class="mim-font">
|
|
Sitosterolemia 1
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
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|
<a href="/entry/210250"> 210250 </a>
|
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|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<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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<p><a href="#2" class="mim-tip-reference" title="Berge, K. E., Tian, H., Graf, G. A., Yu, L., Grishin, N. V., Schultz, J., Kwiterovich, P., Shan, B., Barnes, R., Hobbs, H. H. <strong>Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters.</strong> Science 290: 1771-1775, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11099417/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11099417</a>] [<a href="https://doi.org/10.1126/science.290.5497.1771" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11099417">Berge et al. (2000)</a> identified 2 members of the adenosine triphosphate (ATP)-binding cassette (ABC) transporter family: ABCG8 and ABCG5 (<a href="/entry/605459">605459</a>). ABCG8 and ABCG5 encode deduced proteins of 673 and 651 amino acids, respectively, that share 28% sequence identity. ABCG8 is most similar to ABCG1 (<a href="/entry/603076">603076</a>), which resembles the Drosophila 'white' gene. Both the ABCG8 and ABCG5 proteins contain N-terminal ATP-binding motifs (Walker A and B motifs) and an ABC transporter signature motif (C motif), and both are predicted to contain 6 transmembrane segments in the C terminus. Both are highly expressed in liver and are also detectable in small intestine and colon. Cholesterol feeding induces coordinate increases in levels of Abcg5 and Abcg8 mRNA in mice (<a href="#2" class="mim-tip-reference" title="Berge, K. E., Tian, H., Graf, G. A., Yu, L., Grishin, N. V., Schultz, J., Kwiterovich, P., Shan, B., Barnes, R., Hobbs, H. H. <strong>Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters.</strong> Science 290: 1771-1775, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11099417/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11099417</a>] [<a href="https://doi.org/10.1126/science.290.5497.1771" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11099417">Berge et al., 2000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11099417" 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>Like the ABCG5 gene, the ABCG8 gene contains 13 exons and spans about 28 kb (<a href="#2" class="mim-tip-reference" title="Berge, K. E., Tian, H., Graf, G. A., Yu, L., Grishin, N. V., Schultz, J., Kwiterovich, P., Shan, B., Barnes, R., Hobbs, H. H. <strong>Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters.</strong> Science 290: 1771-1775, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11099417/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11099417</a>] [<a href="https://doi.org/10.1126/science.290.5497.1771" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11099417">Berge et al., 2000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11099417" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="#7" class="mim-tip-reference" title="Lee, J.-Y., Kinch, L. N., Borek, D. M., Wang, J., Wang, J., Urbatsch, I. L., Xie, X.-S., Grishin, N. V., Cohen, J. C., Otwinowski, Z., Hobbs, H. H., Rosenbaum, D. M. <strong>Crystal structure of the human sterol transporter ABCG5/ABCG8.</strong> Nature 533: 561-564, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27144356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27144356</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27144356[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/nature17666" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27144356">Lee et al. (2016)</a> used crystallization in lipid bilayers to determine the x-ray structure of the human ABCG5/ABCG8 heterodimer in a nucleotide-free state at 3.9-angstrom resolution, generating the first atomic model of an ABC sterol transporter. The structure revealed a novel transmembrane fold that is present in a large and functionally diverse superfamily of ABC transporters. The transmembrane domains are coupled to the nucleotide binding sites by networks of interactions that differ between the active and inactive ATPases, reflecting the catalytic asymmetry of the transporter. <a href="#7" class="mim-tip-reference" title="Lee, J.-Y., Kinch, L. N., Borek, D. M., Wang, J., Wang, J., Urbatsch, I. L., Xie, X.-S., Grishin, N. V., Cohen, J. C., Otwinowski, Z., Hobbs, H. H., Rosenbaum, D. M. <strong>Crystal structure of the human sterol transporter ABCG5/ABCG8.</strong> Nature 533: 561-564, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27144356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27144356</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27144356[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/nature17666" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27144356">Lee et al. (2016)</a> concluded that the ABCG5/ABCG8 structure provides a mechanistic framework for understanding sterol transport and the disruptive effects of mutations causing sitosterolemia (see <a href="/entry/615460">615460</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27144356" 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="#2" class="mim-tip-reference" title="Berge, K. E., Tian, H., Graf, G. A., Yu, L., Grishin, N. V., Schultz, J., Kwiterovich, P., Shan, B., Barnes, R., Hobbs, H. H. <strong>Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters.</strong> Science 290: 1771-1775, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11099417/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11099417</a>] [<a href="https://doi.org/10.1126/science.290.5497.1771" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11099417">Berge et al. (2000)</a> identified the ABCG8 and ABCG5 genes on chromosome 2p21 between markers D2S177 and D2S119. The 2 genes are tandemly arrayed in a head-to-head orientation separated by 374 basepairs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11099417" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><strong><em>Sitosterolemia 1</em></strong></p><p>
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In patients with sitosterolemia-1 (STSL1; <a href="/entry/210250">210250</a>) and STSL2 (<a href="/entry/618666">618666</a>), <a href="#2" class="mim-tip-reference" title="Berge, K. E., Tian, H., Graf, G. A., Yu, L., Grishin, N. V., Schultz, J., Kwiterovich, P., Shan, B., Barnes, R., Hobbs, H. H. <strong>Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters.</strong> Science 290: 1771-1775, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11099417/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11099417</a>] [<a href="https://doi.org/10.1126/science.290.5497.1771" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11099417">Berge et al. (2000)</a> identified multiple mutations in the ABCG8 gene and 1 mutation in the ABCG5 gene, respectively. All mutations in the ABCG8 gene were found in homozygosity or compound heterozygosity, consistent with the autosomal recessive nature of the disorder. Nonsense and missense mutations were identified. <a href="#2" class="mim-tip-reference" title="Berge, K. E., Tian, H., Graf, G. A., Yu, L., Grishin, N. V., Schultz, J., Kwiterovich, P., Shan, B., Barnes, R., Hobbs, H. H. <strong>Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters.</strong> Science 290: 1771-1775, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11099417/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11099417</a>] [<a href="https://doi.org/10.1126/science.290.5497.1771" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11099417">Berge et al. (2000)</a> concluded from their data that ABCG5 and ABCG8 normally cooperate to limit intestinal absorption and to promote biliary excretion of sterols, and that mutated forms of these transporters predispose to sterol accumulation and atherosclerosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11099417" 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="Lu, K., Lee, M.-H., Hazard, S., Brooks-Wilson, A., Hidaka, H., Kojima, H., Ose, L., Stalenhoef, A. F. H., Mietinnen, T., Bjorkhem, I., Bruckert, E., Pandya, A., Brewer, H. B., Jr., Salen, G., Dean, M., Srivastava, A., Patel, S. B. <strong>Two genes that map to the STSL locus cause sitosterolemia: genomic structure and spectrum of mutations involving sterolin-1 and sterolin-2, encoded by ABCG5 and ABCG8, respectively.</strong> Am. J. Hum. Genet. 69: 278-290, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11452359/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11452359</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11452359[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/10.1086/321294" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11452359">Lu et al. (2001)</a> provided a detailed characterization of the molecular defects in a very large multiethnic cohort of patients with sitosterolemia. All affected individuals in 37 families carried a mutation in either ABCG5 or ABCG8 but not in both. Clinically, there were no readily apparent features that differentiated individuals with mutations in sterolin-1 versus sterolin-2. The authors suggested that these 2 proteins either act as functional heterodimers or are tightly coupled along a pathway that regulates dietary sterol absorption. Thus, complete loss of any of the sterolins will lead to a functional deficiency. An individual who, hypothetically, carries a mutation in 1 copy of ABCG5 and in 1 copy of ABCG8 may not have sitosterolemia, since he or she would be predicted to have 25% or more normally functioning sterolins. Consistent with this interpretation, the obligate heterozygous parents of the probands did not appear to manifest any clinical or biochemical features, although they were predicted to have 50% normally functioning sterolins. All Japanese probands appeared to have mutations in the ABCG5 gene only; however, mutations in ABCG5 were not exclusively limited to the Japanese. Despite the presence of only 1 known consanguineous marriage, there was a very high degree of homozygosity for informative markers around the 2 loci and evidence of linkage disequilibrium. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11452359" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 59-year-old Corsican woman with sitosterolemia with a hematologic presentation, <a href="#9" class="mim-tip-reference" title="Melenotte, C., Carrie, A., Serratrice, J., Weiller, P.-J. <strong>Sitosterolemia: a new mutation in a Mediterranean patient.</strong> J. Clin. Lipid. 8: 451-454, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25110228/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25110228</a>] [<a href="https://doi.org/10.1016/j.jacl.2014.06.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25110228">Melenotte et al. (2014)</a> identified homozygosity for a nonsense mutation in the ABCG8 gene (Q302X; <a href="#0011">605460.0011</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25110228" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Role in Familial Hypercholesterolemia</em></strong></p><p>
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<a href="#14" class="mim-tip-reference" title="Tada, H., Okada, H., Nomura, A., Yashiro, S., Nohara, A., Ishigaki, Y., Takamura, M., Kawashiri, M. <strong>Rare and deleterious mutations in ABCG5/ABCG8 genes contribute to mimicking and worsening of familial hypercholesterolemia phenotype.</strong> Circ. J. 83: 1917-1924, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31327807/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31327807</a>] [<a href="https://doi.org/10.1253/circj.CJ-19-0317" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31327807">Tada et al. (2019)</a> analyzed 487 patients that met 2 of 3 of the Japanese clinical diagnostic criteria of familial hypercholesterolemia (FH): (1) LDL-C at or above 180 mg/dL; (2) tendon xanthoma; and (3) family history of FH or premature coronary artery disease (CAD) among a patient's second-degree relatives. They identified 276 individuals (57%) with mutations in 1 FH gene (LDLR, <a href="/entry/606945">606945</a>; PCSK9, <a href="/entry/607786">607786</a>; or APOB, <a href="/entry/107730">107730</a>) and no causative mutations in 156 patients (32%). Mutations in ABCG5 or ABCG8 were found in 37 patients (8%) without FH gene mutations; 3 of the 37 patients had sitosterolemia (0.8%) with biallelic mutations. Eighteen patients (4%) had a mutation in an FH gene as well as an ABCG5 or ABCG8 mutation, which was designated as the ABCG5/8 oligogenic FH group. LDL-C was significantly higher in patients with mutations in the ABCG5/8 oligogenic FH group than in patients with only an FH gene mutation (266 vs 234 mg/dl, p less that 0.05). <a href="#14" class="mim-tip-reference" title="Tada, H., Okada, H., Nomura, A., Yashiro, S., Nohara, A., Ishigaki, Y., Takamura, M., Kawashiri, M. <strong>Rare and deleterious mutations in ABCG5/ABCG8 genes contribute to mimicking and worsening of familial hypercholesterolemia phenotype.</strong> Circ. J. 83: 1917-1924, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31327807/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31327807</a>] [<a href="https://doi.org/10.1253/circj.CJ-19-0317" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31327807">Tada et al. (2019)</a> concluded that mutations in ABCG5 or ABCG8 cause at least a portion of FH and may exacerbate FH due to higher LDL-C. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31327807" 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="#11" class="mim-tip-reference" title="Reeskamp, L. F., Volta, A., Zuurbier, L., Defesche, J. C., Kees Hovingh, G., Grefhorst, A. <strong>ABCG5 and ABCG8 genetic variants in familial hypercholesterolemia.</strong> J. Clin. Lipid. 14: 207-217, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32088153/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32088153</a>] [<a href="https://doi.org/10.1016/j.jacl.2020.01.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32088153">Reeskamp et al. (2020)</a> used next-generation sequencing of 3,031 patients referred for familial hypercholesterolemia. Multiple genes were sequenced, including LDLR, APOB, PCSK9, ABCG5, and ABCG8. The frequency of likely heterozygous pathogenic mutations in the FH patients varied from 346 patients (11.42%) with LDLR mutations to 48 patients (1.48%) with ABCG8 mutations and 29 patients (0.96%) with ABCG5 mutations. LDL-C levels were significantly lower in heterozygous carriers of a likely pathogenic ABCG5 or ABCG8 mutation compared to LDLR mutation carriers (6.2 +/- 1.7 vs 7.2 +/- 1.7 mmol/L, P less than .001). In contrast to <a href="#14" class="mim-tip-reference" title="Tada, H., Okada, H., Nomura, A., Yashiro, S., Nohara, A., Ishigaki, Y., Takamura, M., Kawashiri, M. <strong>Rare and deleterious mutations in ABCG5/ABCG8 genes contribute to mimicking and worsening of familial hypercholesterolemia phenotype.</strong> Circ. J. 83: 1917-1924, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31327807/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31327807</a>] [<a href="https://doi.org/10.1253/circj.CJ-19-0317" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31327807">Tada et al. (2019)</a>, who found that patients with an ABCG5 or ABCG8 mutation and a mutation in another FH gene had higher LDL-C levels, <a href="#11" class="mim-tip-reference" title="Reeskamp, L. F., Volta, A., Zuurbier, L., Defesche, J. C., Kees Hovingh, G., Grefhorst, A. <strong>ABCG5 and ABCG8 genetic variants in familial hypercholesterolemia.</strong> J. Clin. Lipid. 14: 207-217, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32088153/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32088153</a>] [<a href="https://doi.org/10.1016/j.jacl.2020.01.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32088153">Reeskamp et al. (2020)</a> found that heterozygosity for ABCG5 or ABCG8 variants with an additional LDLR mutation did not contribute to higher LDL-C levels (p = 0.259). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=31327807+32088153" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Susceptibility to Gallstone Disease</em></strong></p><p>
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<a href="#4" class="mim-tip-reference" title="Buch, S., Schafmayer, C., Volzke, H., Becker, C., Franke, A., von Eller-Eberstein, H., Kluck, C., Bassmann, I., Brosch, M., Lammert, F., Miquel, J. F., Nervi, F., and 15 others. <strong>A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease.</strong> Nature Genet. 39: 995-999, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17632509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17632509</a>] [<a href="https://doi.org/10.1038/ng2101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17632509">Buch et al. (2007)</a> identified a SNP (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs11887534;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs11887534</a>) in the ABCG8 gene (D19H; <a href="#0009">605460.0009</a>) that was associated with gallstone disease (see GBD4, <a href="/entry/611465">611465</a>) in several patient cohorts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17632509" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#12" class="mim-tip-reference" title="Repa, J. J., Berge, K. E., Pomajzl, C., Richardson, J. A., Hobbs, H., Mangelsdorf, D. J. <strong>Regulation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 by the liver X receptors alpha and beta.</strong> J. Biol. Chem. 277: 18793-18800, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11901146/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11901146</a>] [<a href="https://doi.org/10.1074/jbc.M109927200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11901146">Repa et al. (2002)</a> presented evidence for the direct control of the ATP-binding cassette sterol transporters Abca1, Abcg5, and Abcg8 by the liver X receptors (LXRA, <a href="/entry/602423">602423</a>; LXRB, <a href="/entry/600380">600380</a>). By in situ localization of normal mouse sections, they found that expression of Abcg5 and Abcg8 was localized to hepatocytes of the liver and showed a uniform distribution across the hepatic lobule; in jejunal sections, expression was detected exclusively in enterocytes lining the villi. In comparison, expression of Abca1 was found predominantly in lamina propria and occasionally in enterocytes. The intensity of hepatic and jejunal staining for Abcg5/g8 and Abca1 was increased in normal mice fed cholesterol or other Lxr agonists. Cholesterol feeding resulted in upregulation of Abcg5 and Abcg8 in the Lxrb null mice, but not in the Lxra null or double knockout mice, suggesting that Lxra is required for sterol upregulation of Abcg5/g8 in this model. In a rat hepatoma cell line, Lxr-dependent transcription of the Abcg5/g8 genes was cycloheximide-resistant, indicating that these genes are directly regulated by the liver X receptors. <a href="#12" class="mim-tip-reference" title="Repa, J. J., Berge, K. E., Pomajzl, C., Richardson, J. A., Hobbs, H., Mangelsdorf, D. J. <strong>Regulation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 by the liver X receptors alpha and beta.</strong> J. Biol. Chem. 277: 18793-18800, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11901146/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11901146</a>] [<a href="https://doi.org/10.1074/jbc.M109927200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11901146">Repa et al. (2002)</a> concluded that the data provide evidence that Abca1, Abcg5, and Abcg8 are expressed in absorptive enterocytes and that all 3 ABC transporters have a role in regulating cholesterol flux in the intestine. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11901146" 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 Abcg5/Abcg8-deficient mice, <a href="#15" class="mim-tip-reference" title="Yang, C., Yu, L., Li, W., Xu, F., Cohen, J. C., Hobbs, H. H. <strong>Disruption of cholesterol homeostasis by plant sterols.</strong> J. Clin. Invest. 114: 813-822, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15372105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15372105</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15372105[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/10.1172/JCI22186" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15372105">Yang et al. (2004)</a> demonstrated that accumulation of plant sterols perturbed cholesterol homeostasis in the adrenal gland, with a 91% reduction in its cholesterol content. Despite very low cholesterol levels, there was no compensatory increase in cholesterol synthesis or in lipoprotein receptor expression. Adrenal cholesterol levels returned to near-normal levels in mice treated with ezetimibe, which blocks phytosterol absorption. In cultured adrenal cells, stigmasterol but not sitosterol inhibited SREBP2 (<a href="/entry/600481">600481</a>) processing and reduced cholesterol synthesis; stigmasterol also activated the liver X receptor in a cell-based reporter assay. <a href="#15" class="mim-tip-reference" title="Yang, C., Yu, L., Li, W., Xu, F., Cohen, J. C., Hobbs, H. H. <strong>Disruption of cholesterol homeostasis by plant sterols.</strong> J. Clin. Invest. 114: 813-822, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15372105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15372105</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15372105[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/10.1172/JCI22186" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15372105">Yang et al. (2004)</a> concluded that selected dietary plant sterols disrupt cholesterol homeostasis by affecting 2 critical regulatory pathways of lipid metabolism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15372105" 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> rs137852987 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852987;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/rs137852987?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=rs137852987" 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=rs137852987" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a German Swiss patient with sitosterolemia (STSL1; <a href="/entry/210250">210250</a>), the first to be described with this disorder (<a href="#3" class="mim-tip-reference" title="Bhattacharyya, A. K., Connor, W. E. <strong>Beta-sitosterolemia and xanthomatosis: a newly described lipid storage disease in two sisters.</strong> J. Clin. Invest. 53: 1033-1043, 1974.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4360855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4360855</a>] [<a href="https://doi.org/10.1172/JCI107640" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4360855">Bhattacharyya and Connor, 1974</a>), <a href="#2" class="mim-tip-reference" title="Berge, K. E., Tian, H., Graf, G. A., Yu, L., Grishin, N. V., Schultz, J., Kwiterovich, P., Shan, B., Barnes, R., Hobbs, H. H. <strong>Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters.</strong> Science 290: 1771-1775, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11099417/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11099417</a>] [<a href="https://doi.org/10.1126/science.290.5497.1771" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11099417">Berge et al. (2000)</a> identified a homozygous G-to-A transition at nucleotide 1083 in the ABCG8 gene, resulting in a trp361-to-ter (W361X) substitution. The patient's cholesterol was 195 mg/dl. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4360855+11099417" 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 studies of a multiethnic cohort of patients with sitosterolemia, <a href="#8" class="mim-tip-reference" title="Lu, K., Lee, M.-H., Hazard, S., Brooks-Wilson, A., Hidaka, H., Kojima, H., Ose, L., Stalenhoef, A. F. H., Mietinnen, T., Bjorkhem, I., Bruckert, E., Pandya, A., Brewer, H. B., Jr., Salen, G., Dean, M., Srivastava, A., Patel, S. B. <strong>Two genes that map to the STSL locus cause sitosterolemia: genomic structure and spectrum of mutations involving sterolin-1 and sterolin-2, encoded by ABCG5 and ABCG8, respectively.</strong> Am. J. Hum. Genet. 69: 278-290, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11452359/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11452359</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11452359[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/10.1086/321294" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11452359">Lu et al. (2001)</a> found that 19 of 49 mutant alleles of the ABCG8 gene carried the trp361-to-ter mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11452359" 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="Rees, D. C., Iolascon, A., Carella, M., O'Marcaigh, A. S., Kendra, J. R., Jowitt, S. N., Wales, J. K., Vora, A., Makris, M., Manning, N., Nicolaou, A., Fisher, J., Mann, A., Machin, S. J., Clayton, P. T., Gasparini, P., Stewart, G. W. <strong>Stomatocytic haemolysis and macrothrombocytopenia (Mediterranean stomatocytosis/macrothrombocytopenia) is the haematological presentation of phytosterolaemia.</strong> Brit. J. Haemat. 130: 297-309, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16029460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16029460</a>] [<a href="https://doi.org/10.1111/j.1365-2141.2005.05599.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16029460">Rees et al. (2005)</a> identified homozygosity for the W361X mutation in 2 unrelated patients with sitosterolemia. One patient presented with postsurgical bleeding tendency and xanthomata. Both had evidence of mild hemolytic anemia with reticulocytosis, as well as increased platelet volume. <a href="#10" class="mim-tip-reference" title="Rees, D. C., Iolascon, A., Carella, M., O'Marcaigh, A. S., Kendra, J. R., Jowitt, S. N., Wales, J. K., Vora, A., Makris, M., Manning, N., Nicolaou, A., Fisher, J., Mann, A., Machin, S. J., Clayton, P. T., Gasparini, P., Stewart, G. W. <strong>Stomatocytic haemolysis and macrothrombocytopenia (Mediterranean stomatocytosis/macrothrombocytopenia) is the haematological presentation of phytosterolaemia.</strong> Brit. J. Haemat. 130: 297-309, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16029460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16029460</a>] [<a href="https://doi.org/10.1111/j.1365-2141.2005.05599.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16029460">Rees et al. (2005)</a> noted that the phenotype was reminiscent of so-called Mediterranean stomatocytosis/macrothrombocytopenia (see <a href="/entry/210250">210250</a>), and that the results indicated that these hematologic features are part of the manifestation of sitosterolemia, perhaps due to abnormal membrane lipid content in red cells and platelets. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16029460" 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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ABCG8, GLY574ARG
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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> rs137852988 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852988;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/rs137852988?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=rs137852988" 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=rs137852988" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005256 OR RCV000726168 OR RCV000993692 OR RCV002408452 OR RCV003407278" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005256, RCV000726168, RCV000993692, RCV002408452, RCV003407278" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005256...</a>
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<p>In an Amish American patient with sitosterolemia (STSL1; <a href="/entry/210250">210250</a>), <a href="#2" class="mim-tip-reference" title="Berge, K. E., Tian, H., Graf, G. A., Yu, L., Grishin, N. V., Schultz, J., Kwiterovich, P., Shan, B., Barnes, R., Hobbs, H. H. <strong>Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters.</strong> Science 290: 1771-1775, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11099417/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11099417</a>] [<a href="https://doi.org/10.1126/science.290.5497.1771" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11099417">Berge et al. (2000)</a> identified a G-to-A transition at nucleotide 1720 of the ABCG8 gene, resulting in a gly574-to-arg (G574R) substitution. The patient died of coronary artery disease at 13 years of age. This patient was the proband of the extensive Amish kindred studied by <a href="#1" class="mim-tip-reference" title="Beaty, T. H., Kwiterovich, P. O., Jr., Khoury, M. J., White, S., Bachorik, P. S., Smith, H. H., Teng, B., Sniderman, A. <strong>Genetic analysis of plasma sitosterol, apoprotein B, and lipoproteins in a large Amish pedigree with sitosterolemia.</strong> Am. J. Hum. Genet. 38: 492-504, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3706300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3706300</a>]" pmid="3706300">Beaty et al. (1986)</a> and also by <a href="#6" class="mim-tip-reference" title="Kwiterovich, P. O., Jr., Bachorik, P. S., Smith, H. H., McKusick, V. A., Connor, W. E., Teng, B., Sniderman, A. D. <strong>Hyperapobetalipoproteinaemia in two families with xanthomas and phytosterolaemia.</strong> Lancet 317: 466-469, 1981. Note: Originally Volume 1.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6110091/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6110091</a>] [<a href="https://doi.org/10.1016/s0140-6736(81)91850-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6110091">Kwiterovich et al., 1981</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3706300+6110091+11099417" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a Swiss woman with sitosterolemia who had typical xanthomas and also mitral and aortic valvular disease, <a href="#13" class="mim-tip-reference" title="Solca, C., Stanga, Z., Pandit, B., Diem, P., Greeve, J., Patel, S. B. <strong>Sitosterolaemia in Switzerland: molecular genetics links the US Amish-Mennonites to their European roots.</strong> Clin. Genet. 68: 174-178, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15996216/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15996216</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15996216[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/10.1111/j.1399-0004.2005.00472.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15996216">Solca et al. (2005)</a> identified homozygosity for the G574R mutation in the ABCG8 gene. Extended haplotype analysis of this patient and 2 Amish-Mennonite patients with the same mutation revealed that the Swiss patient and 1 Amish-Mennonite patient had identical SNPs, with minor differences between the 2 Amish-Mennonite patients. <a href="#13" class="mim-tip-reference" title="Solca, C., Stanga, Z., Pandit, B., Diem, P., Greeve, J., Patel, S. B. <strong>Sitosterolaemia in Switzerland: molecular genetics links the US Amish-Mennonites to their European roots.</strong> Clin. Genet. 68: 174-178, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15996216/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15996216</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15996216[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/10.1111/j.1399-0004.2005.00472.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15996216">Solca et al. (2005)</a> concluded that the G574R mutation in the Amish-Mennonite population originated in Europe more than 250 years ago. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15996216" 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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<span class="mim-font">
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<strong>.0003 SITOSTEROLEMIA 1</strong>
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ABCG8, TYR658TER
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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> rs137852989 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852989;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/rs137852989?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=rs137852989" 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=rs137852989" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005257 OR RCV000593346 OR RCV004742213 OR RCV004766981" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005257, RCV000593346, RCV004742213, RCV004766981" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005257...</a>
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<span class="mim-text-font">
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<p>In an 8-month-old Caucasian American with sitosterolemia (STSL1; <a href="/entry/210250">210250</a>), <a href="#2" class="mim-tip-reference" title="Berge, K. E., Tian, H., Graf, G. A., Yu, L., Grishin, N. V., Schultz, J., Kwiterovich, P., Shan, B., Barnes, R., Hobbs, H. H. <strong>Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters.</strong> Science 290: 1771-1775, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11099417/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11099417</a>] [<a href="https://doi.org/10.1126/science.290.5497.1771" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11099417">Berge et al. (2000)</a> identified a C-to-G transversion at nucleotide 1974 of the ABCG8 gene, resulting in a tyr658-to-ter substitution. The child was compound heterozygous for the W361X mutation (<a href="#0001">605460.0001</a>). The cholesterol fell from 800 to 151 mg/dl on a low cholesterol diet. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11099417" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0004" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0004 SITOSTEROLEMIA 1</strong>
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ABCG8, ARG263GLN
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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> rs137852990 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852990;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/rs137852990?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=rs137852990" 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=rs137852990" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005258 OR RCV000727975 OR RCV003407279 OR RCV004984635" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005258, RCV000727975, RCV003407279, RCV004984635" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005258...</a>
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<p>In a Chinese child with sitosterolemia (STSL1; <a href="/entry/210250">210250</a>), <a href="#2" class="mim-tip-reference" title="Berge, K. E., Tian, H., Graf, G. A., Yu, L., Grishin, N. V., Schultz, J., Kwiterovich, P., Shan, B., Barnes, R., Hobbs, H. H. <strong>Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters.</strong> Science 290: 1771-1775, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11099417/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11099417</a>] [<a href="https://doi.org/10.1126/science.290.5497.1771" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11099417">Berge et al. (2000)</a> identified a G-to-A transition at nucleotide 788 of the ABCG8 gene, resulting in an arg263-to-gln substitution. The other allele had a deletion of C at nucleotide 547 resulting in termination at codon 191 (<a href="#0005">605460.0005</a>). The child's cholesterol was 556 mg/dl. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11099417" 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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ABCG8, 1-BP DEL, 547C
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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> rs387906323 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906323;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/rs387906323?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=rs387906323" 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=rs387906323" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005259 OR RCV000726960" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005259, RCV000726960" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005259...</a>
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<p>For discussion of the 1-bp deletion in the ABCG8 gene (547delC) that was found in compound heterozygous state in a patient with sitosterolemia (STSL1; <a href="/entry/210250">210250</a>) by <a href="#2" class="mim-tip-reference" title="Berge, K. E., Tian, H., Graf, G. A., Yu, L., Grishin, N. V., Schultz, J., Kwiterovich, P., Shan, B., Barnes, R., Hobbs, H. H. <strong>Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters.</strong> Science 290: 1771-1775, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11099417/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11099417</a>] [<a href="https://doi.org/10.1126/science.290.5497.1771" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11099417">Berge et al. (2000)</a>, see <a href="#0004">605460.0004</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11099417" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0006" class="mim-anchor"></a>
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<strong>.0006 SITOSTEROLEMIA 1</strong>
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ABCG8, ARG412TER
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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> rs137852991 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852991;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/rs137852991?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=rs137852991" 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=rs137852991" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005260 OR RCV000993691 OR RCV001699176 OR RCV003298028 OR RCV003952343" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005260, RCV000993691, RCV001699176, RCV003298028, RCV003952343" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005260...</a>
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<p>In a Caucasian American child with sitosterolemia (STSL1; <a href="/entry/210250">210250</a>), <a href="#2" class="mim-tip-reference" title="Berge, K. E., Tian, H., Graf, G. A., Yu, L., Grishin, N. V., Schultz, J., Kwiterovich, P., Shan, B., Barnes, R., Hobbs, H. H. <strong>Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters.</strong> Science 290: 1771-1775, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11099417/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11099417</a>] [<a href="https://doi.org/10.1126/science.290.5497.1771" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11099417">Berge et al. (2000)</a> identified a C-to-T transition at nucleotide 1234 of the ABCG8 gene, resulting in an arg412-to-ter substitution. The child was a compound heterozygote for the W361X mutation (<a href="#0001">605460.0001</a>). The child's cholesterol fell from 375 to 201 mg/dl on a low cholesterol diet. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11099417" 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>.0007 SITOSTEROLEMIA 1</strong>
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ABCG8, LEU596ARG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852992 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852992;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852992" 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=rs137852992" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005261" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005261" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005261</a>
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<p>In a Caucasian American child with sitosterolemia (STSL1; <a href="/entry/210250">210250</a>), <a href="#2" class="mim-tip-reference" title="Berge, K. E., Tian, H., Graf, G. A., Yu, L., Grishin, N. V., Schultz, J., Kwiterovich, P., Shan, B., Barnes, R., Hobbs, H. H. <strong>Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters.</strong> Science 290: 1771-1775, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11099417/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11099417</a>] [<a href="https://doi.org/10.1126/science.290.5497.1771" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11099417">Berge et al. (2000)</a> identified a T-to-G transversion at nucleotide 1787 of the ABCG8 gene, resulting in a leu596-to-arg substitution. A mutation was not identified on the other allele. The child's cholesterol fell from 753 to 106 mg/dl on a low cholesterol diet. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11099417" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0008" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0008 SITOSTEROLEMIA 1</strong>
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ABCG8, PRO231THR
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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> rs137852993 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852993;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/rs137852993?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=rs137852993" 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=rs137852993" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005262" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005262" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005262</a>
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<span class="mim-text-font">
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<p>In a Mexican American patient with sitosterolemia (STSL1; <a href="/entry/210250">210250</a>), <a href="#2" class="mim-tip-reference" title="Berge, K. E., Tian, H., Graf, G. A., Yu, L., Grishin, N. V., Schultz, J., Kwiterovich, P., Shan, B., Barnes, R., Hobbs, H. H. <strong>Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters.</strong> Science 290: 1771-1775, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11099417/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11099417</a>] [<a href="https://doi.org/10.1126/science.290.5497.1771" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11099417">Berge et al. (2000)</a> identified an A-to-C transversion at nucleotide 691 of the ABCG8 gene, resulting in a pro231-to-thr substitution. The patient was a compound heterozygote for the arg412-to-ter mutation (R412X; <a href="#0006">605460.0006</a>). The patient's LDL cholesterol fell from 380 to 280 mg/dl. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11099417" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0009" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0009 GALLBLADDER DISEASE 4</strong>
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<div style="float: left;">
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ABCG8, ASP19HIS
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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> rs11887534 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs11887534;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/rs11887534?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=rs11887534" 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=rs11887534" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005263 OR RCV000266053 OR RCV000269126 OR RCV001094725 OR RCV001705581 OR RCV002345232 OR RCV002490320 OR RCV003982825" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005263, RCV000266053, RCV000269126, RCV001094725, RCV001705581, RCV002345232, RCV002490320, RCV003982825" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005263...</a>
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</span>
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<div>
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<span class="mim-text-font">
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<p><a href="#4" class="mim-tip-reference" title="Buch, S., Schafmayer, C., Volzke, H., Becker, C., Franke, A., von Eller-Eberstein, H., Kluck, C., Bassmann, I., Brosch, M., Lammert, F., Miquel, J. F., Nervi, F., and 15 others. <strong>A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease.</strong> Nature Genet. 39: 995-999, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17632509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17632509</a>] [<a href="https://doi.org/10.1038/ng2101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17632509">Buch et al. (2007)</a> identified a SNP (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs11887534;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs11887534</a>) in the ABCG8 gene, a G-to-C transversion corresponding to an asp19-to-his (D19H) substitution, that was significantly associated with gallstones (GBD4; <a href="/entry/611465">611465</a>) in 3 replication studies. In an initial genomewide screening panel among 280 affected individuals and 360 controls, the authors identified 235 significant SNPs, including D19H. A follow-up study in 1,105 additional affected individuals replicated the disease association of D19H (p = 4.1 x 10(-9), 1.1 x 10(-4) after Bonferroni correction). Additional significant replication was achieved in 728 Germans (p = 2.8 x 10(-7)). The overall odds ratio in the full German sample was 2.2 and 7.1 for heterozygous and homozygous H allele carriers, respectively, corresponding to a population risk of about 11%. The association was stronger in those with cholesterol gallstones, suggesting that his19 may be associated with increased efficiency of cholesterol transport into the bile lumen, causing cholesterol hypersaturation of bile and promoting the formation of gallstones. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17632509" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0010" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0010 SITOSTEROLEMIA 1</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<div style="float: left;">
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ABCG8, SER107TER (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137854891;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs137854891</a>)
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137854891 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137854891;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/rs137854891?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=rs137854891" 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=rs137854891" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000032718 OR RCV001384588" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032718, RCV001384588" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032718...</a>
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<p>In 4 Schmiedeleut (S-leut) Hutterite individuals with sitosterolemia (STSL1; <a href="/entry/210250">210250</a>), <a href="#5" class="mim-tip-reference" title="Chong, J. X., Ouwenga, R., Anderson, R. L., Waggoner, D. J., Ober, C. <strong>A population-based study of autosomal-recessive disease-causing mutations in a founder population.</strong> Am. J. Hum. Genet. 91: 608-620, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22981120/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22981120</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22981120[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2012.08.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22981120">Chong et al. (2012)</a> identified a homozygous C-to-G transition at nucleotide 320 of the ABCG8 gene, resulting in a ser-to-ter substitution at codon 107 (S107X). All 4 individuals (2 teenaged sibs and 2 adult sibs) had elevated sitosterol levels (4.29-19.0 mg/100ml). The mutation was identified in a carrier screening for mutations resulting in autosomal recessive disorders among 1,644 S-leut Hutterites in the United States. The mutation, private to the Hutterite population, was found in heterozygosity in 127 individuals and homozygosity in 4 among 1,515 screened, giving a carrier frequency among the Hutterites of 0.084, or 1 in 12. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22981120" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0011" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0011 SITOSTEROLEMIA 1</strong>
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</h4>
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ABCG8, GLN302TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1668974150 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1668974150;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1668974150" 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=rs1668974150" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV001248858" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001248858" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001248858</a>
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<p>In a 59-year-old Corsican woman with sitosterolemia-1 (STSL1; <a href="/entry/210250">210250</a>) who had premature atherosclerotic disease and hemolytic anemia with macrothrombocytopenia, <a href="#9" class="mim-tip-reference" title="Melenotte, C., Carrie, A., Serratrice, J., Weiller, P.-J. <strong>Sitosterolemia: a new mutation in a Mediterranean patient.</strong> J. Clin. Lipid. 8: 451-454, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25110228/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25110228</a>] [<a href="https://doi.org/10.1016/j.jacl.2014.06.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25110228">Melenotte et al. (2014)</a> identified a homozygous c.904C-T transition (c.904C-T, NM_022437.2) in the ABCG8 gene, resulting in a gln302-to-ter (Q302X) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25110228" 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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<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>REFERENCES</strong>
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</h4>
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[<a href="https://doi.org/10.1126/science.290.5497.1771" target="_blank">Full Text</a>]
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<a id="Bhattacharyya1974" class="mim-anchor"></a>
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Bhattacharyya, A. K., Connor, W. E.
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[<a href="https://doi.org/10.1172/JCI107640" target="_blank">Full Text</a>]
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<a id="Buch2007" class="mim-anchor"></a>
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Buch, S., Schafmayer, C., Volzke, H., Becker, C., Franke, A., von Eller-Eberstein, H., Kluck, C., Bassmann, I., Brosch, M., Lammert, F., Miquel, J. F., Nervi, F., and 15 others.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17632509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17632509</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17632509" 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/ng2101" target="_blank">Full Text</a>]
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<a id="Chong2012" class="mim-anchor"></a>
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Chong, J. X., Ouwenga, R., Anderson, R. L., Waggoner, D. J., Ober, C.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22981120/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22981120</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22981120[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=22981120" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ajhg.2012.08.007" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6110091/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6110091</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6110091" 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/s0140-6736(81)91850-x" target="_blank">Full Text</a>]
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Lee, J.-Y., Kinch, L. N., Borek, D. M., Wang, J., Wang, J., Urbatsch, I. L., Xie, X.-S., Grishin, N. V., Cohen, J. C., Otwinowski, Z., Hobbs, H. H., Rosenbaum, D. M.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27144356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27144356</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27144356[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=27144356" 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/nature17666" target="_blank">Full Text</a>]
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Lu, K., Lee, M.-H., Hazard, S., Brooks-Wilson, A., Hidaka, H., Kojima, H., Ose, L., Stalenhoef, A. F. H., Mietinnen, T., Bjorkhem, I., Bruckert, E., Pandya, A., Brewer, H. B., Jr., Salen, G., Dean, M., Srivastava, A., Patel, S. B.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11452359/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11452359</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11452359[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=11452359" 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/10.1086/321294" target="_blank">Full Text</a>]
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<a id="Melenotte2014" class="mim-anchor"></a>
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<div class="">
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Melenotte, C., Carrie, A., Serratrice, J., Weiller, P.-J.
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<strong>Sitosterolemia: a new mutation in a Mediterranean patient.</strong>
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J. Clin. Lipid. 8: 451-454, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25110228/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25110228</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25110228" 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.jacl.2014.06.003" target="_blank">Full Text</a>]
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<a id="Rees2005" class="mim-anchor"></a>
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Rees, D. C., Iolascon, A., Carella, M., O'Marcaigh, A. S., Kendra, J. R., Jowitt, S. N., Wales, J. K., Vora, A., Makris, M., Manning, N., Nicolaou, A., Fisher, J., Mann, A., Machin, S. J., Clayton, P. T., Gasparini, P., Stewart, G. W.
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<strong>Stomatocytic haemolysis and macrothrombocytopenia (Mediterranean stomatocytosis/macrothrombocytopenia) is the haematological presentation of phytosterolaemia.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16029460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16029460</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16029460" 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/j.1365-2141.2005.05599.x" target="_blank">Full Text</a>]
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<a id="Reeskamp2020" class="mim-anchor"></a>
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Reeskamp, L. F., Volta, A., Zuurbier, L., Defesche, J. C., Kees Hovingh, G., Grefhorst, A.
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<strong>ABCG5 and ABCG8 genetic variants in familial hypercholesterolemia.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32088153/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32088153</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32088153" 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.jacl.2020.01.007" target="_blank">Full Text</a>]
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Repa, J. J., Berge, K. E., Pomajzl, C., Richardson, J. A., Hobbs, H., Mangelsdorf, D. J.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11901146/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11901146</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11901146" 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.M109927200" target="_blank">Full Text</a>]
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Solca, C., Stanga, Z., Pandit, B., Diem, P., Greeve, J., Patel, S. B.
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<strong>Sitosterolaemia in Switzerland: molecular genetics links the US Amish-Mennonites to their European roots.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15996216/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15996216</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15996216[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=15996216" 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/j.1399-0004.2005.00472.x" target="_blank">Full Text</a>]
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<a id="14" class="mim-anchor"></a>
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<a id="Tada2019" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tada, H., Okada, H., Nomura, A., Yashiro, S., Nohara, A., Ishigaki, Y., Takamura, M., Kawashiri, M.
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<strong>Rare and deleterious mutations in ABCG5/ABCG8 genes contribute to mimicking and worsening of familial hypercholesterolemia phenotype.</strong>
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Circ. J. 83: 1917-1924, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31327807/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31327807</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31327807" 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/10.1253/circj.CJ-19-0317" target="_blank">Full Text</a>]
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</p>
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<a id="15" class="mim-anchor"></a>
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<a id="Yang2004" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yang, C., Yu, L., Li, W., Xu, F., Cohen, J. C., Hobbs, H. H.
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<strong>Disruption of cholesterol homeostasis by plant sterols.</strong>
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J. Clin. Invest. 114: 813-822, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15372105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15372105</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15372105[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=15372105" 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/10.1172/JCI22186" target="_blank">Full Text</a>]
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Kelly A. Przylepa - updated : 07/15/2020
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<div class="row collapse" id="mimCollapseContributors">
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<span class="mim-text-font">
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Ada Hamosh - updated : 07/06/2016<br>Ada Hamosh - updated : 2/11/2013<br>Ada Hamosh - updated : 2/7/2013<br>Cassandra L. Kniffin - updated : 11/12/2009<br>Cassandra L. Kniffin - updated : 8/17/2007<br>Marla J. F. O'Neill - updated : 5/24/2006<br>Marla J. F. O'Neill - updated : 10/14/2004<br>Victor A. McKusick - updated : 2/26/2003<br>Patricia A. Hartz - updated : 6/11/2002<br>Victor A. McKusick - updated : 8/30/2001
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<a id="creationDate" class="mim-anchor"></a>
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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Creation Date:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh : 12/7/2000
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 09/25/2022
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carol : 07/17/2020<br>carol : 07/16/2020<br>carol : 07/15/2020<br>carol : 03/17/2020<br>carol : 11/19/2019<br>carol : 08/20/2019<br>alopez : 07/06/2016<br>carol : 1/31/2016<br>mcolton : 2/10/2015<br>alopez : 2/11/2013<br>terry : 2/7/2013<br>carol : 11/16/2009<br>ckniffin : 11/12/2009<br>terry : 6/5/2009<br>alopez : 9/27/2007<br>ckniffin : 8/17/2007<br>ckniffin : 8/17/2007<br>wwang : 5/25/2006<br>terry : 5/24/2006<br>carol : 10/15/2004<br>terry : 10/14/2004<br>alopez : 2/28/2003<br>terry : 2/26/2003<br>carol : 6/11/2002<br>cwells : 9/20/2001<br>cwells : 9/10/2001<br>terry : 8/30/2001<br>carol : 12/19/2000<br>carol : 12/7/2000<br>carol : 12/7/2000
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<span class="mim-font">
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<strong>*</strong> 605460
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<h3>
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ATP-BINDING CASSETTE, SUBFAMILY G, MEMBER 8; ABCG8
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<span class="mim-font">
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STEROLIN 2
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: ABCG8</em></strong>
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Cytogenetic location: 2p21
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Genomic coordinates <span class="small">(GRCh38)</span> : 2:43,838,971-43,882,988 </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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<strong>Gene-Phenotype Relationships</strong>
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<table class="table table-bordered table-condensed small mim-table-padding">
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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<span class="mim-font">
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2p21
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<span class="mim-font">
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{Gallbladder disease 4}
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</td>
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<td>
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<span class="mim-font">
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611465
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<span class="mim-font">
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<span class="mim-font">
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3
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<span class="mim-font">
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Sitosterolemia 1
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<span class="mim-font">
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210250
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<span class="mim-font">
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Autosomal recessive
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<td>
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<span class="mim-font">
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3
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<span class="mim-font">
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<strong>TEXT</strong>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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<span class="mim-text-font">
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<p>Berge et al. (2000) identified 2 members of the adenosine triphosphate (ATP)-binding cassette (ABC) transporter family: ABCG8 and ABCG5 (605459). ABCG8 and ABCG5 encode deduced proteins of 673 and 651 amino acids, respectively, that share 28% sequence identity. ABCG8 is most similar to ABCG1 (603076), which resembles the Drosophila 'white' gene. Both the ABCG8 and ABCG5 proteins contain N-terminal ATP-binding motifs (Walker A and B motifs) and an ABC transporter signature motif (C motif), and both are predicted to contain 6 transmembrane segments in the C terminus. Both are highly expressed in liver and are also detectable in small intestine and colon. Cholesterol feeding induces coordinate increases in levels of Abcg5 and Abcg8 mRNA in mice (Berge et al., 2000). </p>
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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 class="mim-text-font">
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<p>Like the ABCG5 gene, the ABCG8 gene contains 13 exons and spans about 28 kb (Berge et al., 2000). </p>
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<br />
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<h4>
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<span class="mim-font">
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<strong>Biochemical Features</strong>
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<span class="mim-text-font">
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<p><strong><em>Crystal Structure</em></strong></p><p>
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Lee et al. (2016) used crystallization in lipid bilayers to determine the x-ray structure of the human ABCG5/ABCG8 heterodimer in a nucleotide-free state at 3.9-angstrom resolution, generating the first atomic model of an ABC sterol transporter. The structure revealed a novel transmembrane fold that is present in a large and functionally diverse superfamily of ABC transporters. The transmembrane domains are coupled to the nucleotide binding sites by networks of interactions that differ between the active and inactive ATPases, reflecting the catalytic asymmetry of the transporter. Lee et al. (2016) concluded that the ABCG5/ABCG8 structure provides a mechanistic framework for understanding sterol transport and the disruptive effects of mutations causing sitosterolemia (see 615460). </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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<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>Berge et al. (2000) identified the ABCG8 and ABCG5 genes on chromosome 2p21 between markers D2S177 and D2S119. The 2 genes are tandemly arrayed in a head-to-head orientation separated by 374 basepairs. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Sitosterolemia 1</em></strong></p><p>
|
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In patients with sitosterolemia-1 (STSL1; 210250) and STSL2 (618666), Berge et al. (2000) identified multiple mutations in the ABCG8 gene and 1 mutation in the ABCG5 gene, respectively. All mutations in the ABCG8 gene were found in homozygosity or compound heterozygosity, consistent with the autosomal recessive nature of the disorder. Nonsense and missense mutations were identified. Berge et al. (2000) concluded from their data that ABCG5 and ABCG8 normally cooperate to limit intestinal absorption and to promote biliary excretion of sterols, and that mutated forms of these transporters predispose to sterol accumulation and atherosclerosis. </p><p>Lu et al. (2001) provided a detailed characterization of the molecular defects in a very large multiethnic cohort of patients with sitosterolemia. All affected individuals in 37 families carried a mutation in either ABCG5 or ABCG8 but not in both. Clinically, there were no readily apparent features that differentiated individuals with mutations in sterolin-1 versus sterolin-2. The authors suggested that these 2 proteins either act as functional heterodimers or are tightly coupled along a pathway that regulates dietary sterol absorption. Thus, complete loss of any of the sterolins will lead to a functional deficiency. An individual who, hypothetically, carries a mutation in 1 copy of ABCG5 and in 1 copy of ABCG8 may not have sitosterolemia, since he or she would be predicted to have 25% or more normally functioning sterolins. Consistent with this interpretation, the obligate heterozygous parents of the probands did not appear to manifest any clinical or biochemical features, although they were predicted to have 50% normally functioning sterolins. All Japanese probands appeared to have mutations in the ABCG5 gene only; however, mutations in ABCG5 were not exclusively limited to the Japanese. Despite the presence of only 1 known consanguineous marriage, there was a very high degree of homozygosity for informative markers around the 2 loci and evidence of linkage disequilibrium. </p><p>In a 59-year-old Corsican woman with sitosterolemia with a hematologic presentation, Melenotte et al. (2014) identified homozygosity for a nonsense mutation in the ABCG8 gene (Q302X; 605460.0011). </p><p><strong><em>Role in Familial Hypercholesterolemia</em></strong></p><p>
|
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Tada et al. (2019) analyzed 487 patients that met 2 of 3 of the Japanese clinical diagnostic criteria of familial hypercholesterolemia (FH): (1) LDL-C at or above 180 mg/dL; (2) tendon xanthoma; and (3) family history of FH or premature coronary artery disease (CAD) among a patient's second-degree relatives. They identified 276 individuals (57%) with mutations in 1 FH gene (LDLR, 606945; PCSK9, 607786; or APOB, 107730) and no causative mutations in 156 patients (32%). Mutations in ABCG5 or ABCG8 were found in 37 patients (8%) without FH gene mutations; 3 of the 37 patients had sitosterolemia (0.8%) with biallelic mutations. Eighteen patients (4%) had a mutation in an FH gene as well as an ABCG5 or ABCG8 mutation, which was designated as the ABCG5/8 oligogenic FH group. LDL-C was significantly higher in patients with mutations in the ABCG5/8 oligogenic FH group than in patients with only an FH gene mutation (266 vs 234 mg/dl, p less that 0.05). Tada et al. (2019) concluded that mutations in ABCG5 or ABCG8 cause at least a portion of FH and may exacerbate FH due to higher LDL-C. </p><p>Reeskamp et al. (2020) used next-generation sequencing of 3,031 patients referred for familial hypercholesterolemia. Multiple genes were sequenced, including LDLR, APOB, PCSK9, ABCG5, and ABCG8. The frequency of likely heterozygous pathogenic mutations in the FH patients varied from 346 patients (11.42%) with LDLR mutations to 48 patients (1.48%) with ABCG8 mutations and 29 patients (0.96%) with ABCG5 mutations. LDL-C levels were significantly lower in heterozygous carriers of a likely pathogenic ABCG5 or ABCG8 mutation compared to LDLR mutation carriers (6.2 +/- 1.7 vs 7.2 +/- 1.7 mmol/L, P less than .001). In contrast to Tada et al. (2019), who found that patients with an ABCG5 or ABCG8 mutation and a mutation in another FH gene had higher LDL-C levels, Reeskamp et al. (2020) found that heterozygosity for ABCG5 or ABCG8 variants with an additional LDLR mutation did not contribute to higher LDL-C levels (p = 0.259). </p><p><strong><em>Susceptibility to Gallstone Disease</em></strong></p><p>
|
|
Buch et al. (2007) identified a SNP (rs11887534) in the ABCG8 gene (D19H; 605460.0009) that was associated with gallstone disease (see GBD4, 611465) in several patient cohorts. </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>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>Repa et al. (2002) presented evidence for the direct control of the ATP-binding cassette sterol transporters Abca1, Abcg5, and Abcg8 by the liver X receptors (LXRA, 602423; LXRB, 600380). By in situ localization of normal mouse sections, they found that expression of Abcg5 and Abcg8 was localized to hepatocytes of the liver and showed a uniform distribution across the hepatic lobule; in jejunal sections, expression was detected exclusively in enterocytes lining the villi. In comparison, expression of Abca1 was found predominantly in lamina propria and occasionally in enterocytes. The intensity of hepatic and jejunal staining for Abcg5/g8 and Abca1 was increased in normal mice fed cholesterol or other Lxr agonists. Cholesterol feeding resulted in upregulation of Abcg5 and Abcg8 in the Lxrb null mice, but not in the Lxra null or double knockout mice, suggesting that Lxra is required for sterol upregulation of Abcg5/g8 in this model. In a rat hepatoma cell line, Lxr-dependent transcription of the Abcg5/g8 genes was cycloheximide-resistant, indicating that these genes are directly regulated by the liver X receptors. Repa et al. (2002) concluded that the data provide evidence that Abca1, Abcg5, and Abcg8 are expressed in absorptive enterocytes and that all 3 ABC transporters have a role in regulating cholesterol flux in the intestine. </p><p>In Abcg5/Abcg8-deficient mice, Yang et al. (2004) demonstrated that accumulation of plant sterols perturbed cholesterol homeostasis in the adrenal gland, with a 91% reduction in its cholesterol content. Despite very low cholesterol levels, there was no compensatory increase in cholesterol synthesis or in lipoprotein receptor expression. Adrenal cholesterol levels returned to near-normal levels in mice treated with ezetimibe, which blocks phytosterol absorption. In cultured adrenal cells, stigmasterol but not sitosterol inhibited SREBP2 (600481) processing and reduced cholesterol synthesis; stigmasterol also activated the liver X receptor in a cell-based reporter assay. Yang et al. (2004) concluded that selected dietary plant sterols disrupt cholesterol homeostasis by affecting 2 critical regulatory pathways of lipid metabolism. </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>11 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 SITOSTEROLEMIA 1</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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ABCG8, TRP361TER
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<br />
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SNP: rs137852987,
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gnomAD: rs137852987,
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ClinVar: RCV000005255, RCV000255446, RCV000993693, RCV002426490, RCV002504749, RCV003407277
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a German Swiss patient with sitosterolemia (STSL1; 210250), the first to be described with this disorder (Bhattacharyya and Connor, 1974), Berge et al. (2000) identified a homozygous G-to-A transition at nucleotide 1083 in the ABCG8 gene, resulting in a trp361-to-ter (W361X) substitution. The patient's cholesterol was 195 mg/dl. </p><p>In studies of a multiethnic cohort of patients with sitosterolemia, Lu et al. (2001) found that 19 of 49 mutant alleles of the ABCG8 gene carried the trp361-to-ter mutation. </p><p>Rees et al. (2005) identified homozygosity for the W361X mutation in 2 unrelated patients with sitosterolemia. One patient presented with postsurgical bleeding tendency and xanthomata. Both had evidence of mild hemolytic anemia with reticulocytosis, as well as increased platelet volume. Rees et al. (2005) noted that the phenotype was reminiscent of so-called Mediterranean stomatocytosis/macrothrombocytopenia (see 210250), and that the results indicated that these hematologic features are part of the manifestation of sitosterolemia, perhaps due to abnormal membrane lipid content in red cells and platelets. </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 SITOSTEROLEMIA 1</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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ABCG8, GLY574ARG
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<br />
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SNP: rs137852988,
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gnomAD: rs137852988,
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ClinVar: RCV000005256, RCV000726168, RCV000993692, RCV002408452, RCV003407278
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In an Amish American patient with sitosterolemia (STSL1; 210250), Berge et al. (2000) identified a G-to-A transition at nucleotide 1720 of the ABCG8 gene, resulting in a gly574-to-arg (G574R) substitution. The patient died of coronary artery disease at 13 years of age. This patient was the proband of the extensive Amish kindred studied by Beaty et al. (1986) and also by Kwiterovich et al., 1981. </p><p>In a Swiss woman with sitosterolemia who had typical xanthomas and also mitral and aortic valvular disease, Solca et al. (2005) identified homozygosity for the G574R mutation in the ABCG8 gene. Extended haplotype analysis of this patient and 2 Amish-Mennonite patients with the same mutation revealed that the Swiss patient and 1 Amish-Mennonite patient had identical SNPs, with minor differences between the 2 Amish-Mennonite patients. Solca et al. (2005) concluded that the G574R mutation in the Amish-Mennonite population originated in Europe more than 250 years ago. </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 SITOSTEROLEMIA 1</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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ABCG8, TYR658TER
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<br />
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SNP: rs137852989,
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gnomAD: rs137852989,
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ClinVar: RCV000005257, RCV000593346, RCV004742213, RCV004766981
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In an 8-month-old Caucasian American with sitosterolemia (STSL1; 210250), Berge et al. (2000) identified a C-to-G transversion at nucleotide 1974 of the ABCG8 gene, resulting in a tyr658-to-ter substitution. The child was compound heterozygous for the W361X mutation (605460.0001). The cholesterol fell from 800 to 151 mg/dl on a low cholesterol diet. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0004 SITOSTEROLEMIA 1</strong>
|
|
</span>
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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ABCG8, ARG263GLN
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<br />
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SNP: rs137852990,
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gnomAD: rs137852990,
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ClinVar: RCV000005258, RCV000727975, RCV003407279, RCV004984635
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</span>
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</div>
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<div>
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|
<span class="mim-text-font">
|
|
<p>In a Chinese child with sitosterolemia (STSL1; 210250), Berge et al. (2000) identified a G-to-A transition at nucleotide 788 of the ABCG8 gene, resulting in an arg263-to-gln substitution. The other allele had a deletion of C at nucleotide 547 resulting in termination at codon 191 (605460.0005). The child's cholesterol was 556 mg/dl. </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 SITOSTEROLEMIA 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
|
ABCG8, 1-BP DEL, 547C
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|
|
<br />
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|
|
SNP: rs387906323,
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|
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|
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gnomAD: rs387906323,
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|
|
ClinVar: RCV000005259, RCV000726960
|
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|
|
</span>
|
|
</div>
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 1-bp deletion in the ABCG8 gene (547delC) that was found in compound heterozygous state in a patient with sitosterolemia (STSL1; 210250) by Berge et al. (2000), see 605460.0004. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
|
</div>
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</div>
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<div>
|
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 SITOSTEROLEMIA 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCG8, ARG412TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852991,
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|
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|
|
|
gnomAD: rs137852991,
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|
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|
|
ClinVar: RCV000005260, RCV000993691, RCV001699176, RCV003298028, RCV003952343
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Caucasian American child with sitosterolemia (STSL1; 210250), Berge et al. (2000) identified a C-to-T transition at nucleotide 1234 of the ABCG8 gene, resulting in an arg412-to-ter substitution. The child was a compound heterozygote for the W361X mutation (605460.0001). The child's cholesterol fell from 375 to 201 mg/dl on a low cholesterol diet. </p>
|
|
</span>
|
|
</div>
|
|
|
|
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|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 SITOSTEROLEMIA 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCG8, LEU596ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852992,
|
|
|
|
|
|
|
|
ClinVar: RCV000005261
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Caucasian American child with sitosterolemia (STSL1; 210250), Berge et al. (2000) identified a T-to-G transversion at nucleotide 1787 of the ABCG8 gene, resulting in a leu596-to-arg substitution. A mutation was not identified on the other allele. The child's cholesterol fell from 753 to 106 mg/dl on a low cholesterol diet. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
|
</div>
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|
|
</div>
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<div>
|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 SITOSTEROLEMIA 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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|
|
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCG8, PRO231THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852993,
|
|
|
|
|
|
gnomAD: rs137852993,
|
|
|
|
|
|
ClinVar: RCV000005262
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Mexican American patient with sitosterolemia (STSL1; 210250), Berge et al. (2000) identified an A-to-C transversion at nucleotide 691 of the ABCG8 gene, resulting in a pro231-to-thr substitution. The patient was a compound heterozygote for the arg412-to-ter mutation (R412X; 605460.0006). The patient's LDL cholesterol fell from 380 to 280 mg/dl. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
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|
|
<div>
|
|
<br />
|
|
</div>
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|
|
|
</div>
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 GALLBLADDER DISEASE 4</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
ABCG8, ASP19HIS
|
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|
|
|
|
<br />
|
|
|
|
SNP: rs11887534,
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|
|
|
|
|
gnomAD: rs11887534,
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|
|
|
|
|
ClinVar: RCV000005263, RCV000266053, RCV000269126, RCV001094725, RCV001705581, RCV002345232, RCV002490320, RCV003982825
|
|
|
|
|
|
</span>
|
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>Buch et al. (2007) identified a SNP (rs11887534) in the ABCG8 gene, a G-to-C transversion corresponding to an asp19-to-his (D19H) substitution, that was significantly associated with gallstones (GBD4; 611465) in 3 replication studies. In an initial genomewide screening panel among 280 affected individuals and 360 controls, the authors identified 235 significant SNPs, including D19H. A follow-up study in 1,105 additional affected individuals replicated the disease association of D19H (p = 4.1 x 10(-9), 1.1 x 10(-4) after Bonferroni correction). Additional significant replication was achieved in 728 Germans (p = 2.8 x 10(-7)). The overall odds ratio in the full German sample was 2.2 and 7.1 for heterozygous and homozygous H allele carriers, respectively, corresponding to a population risk of about 11%. The association was stronger in those with cholesterol gallstones, suggesting that his19 may be associated with increased efficiency of cholesterol transport into the bile lumen, causing cholesterol hypersaturation of bile and promoting the formation of gallstones. </p>
|
|
</span>
|
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</div>
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<div>
|
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<br />
|
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 SITOSTEROLEMIA 1</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
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|
ABCG8, SER107TER ({dbSNP rs137854891})
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<br />
|
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|
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SNP: rs137854891,
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|
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gnomAD: rs137854891,
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|
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ClinVar: RCV000032718, RCV001384588
|
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|
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In 4 Schmiedeleut (S-leut) Hutterite individuals with sitosterolemia (STSL1; 210250), Chong et al. (2012) identified a homozygous C-to-G transition at nucleotide 320 of the ABCG8 gene, resulting in a ser-to-ter substitution at codon 107 (S107X). All 4 individuals (2 teenaged sibs and 2 adult sibs) had elevated sitosterol levels (4.29-19.0 mg/100ml). The mutation was identified in a carrier screening for mutations resulting in autosomal recessive disorders among 1,644 S-leut Hutterites in the United States. The mutation, private to the Hutterite population, was found in heterozygosity in 127 individuals and homozygosity in 4 among 1,515 screened, giving a carrier frequency among the Hutterites of 0.084, or 1 in 12. </p>
|
|
</span>
|
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</div>
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<div>
|
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<br />
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</div>
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</div>
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<div>
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 SITOSTEROLEMIA 1</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
|
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|
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ABCG8, GLN302TER
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<br />
|
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|
|
SNP: rs1668974150,
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|
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|
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ClinVar: RCV001248858
|
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</span>
|
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</div>
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 59-year-old Corsican woman with sitosterolemia-1 (STSL1; 210250) who had premature atherosclerotic disease and hemolytic anemia with macrothrombocytopenia, Melenotte et al. (2014) identified a homozygous c.904C-T transition (c.904C-T, NM_022437.2) in the ABCG8 gene, resulting in a gln302-to-ter (Q302X) substitution. </p>
|
|
</span>
|
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
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