3525 lines
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Entry
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- *605740 - SCLEROSTIN; SOST
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*605740</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/605740">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000167941;t=ENST00000301691" 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=50964" 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=605740" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000167941;t=ENST00000301691" 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_025237" 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_025237" 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=605740" 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=05762&isoform_id=05762_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/SOST" 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/13161011,13161020,13236418,13376846,20140220,33337958,33338190,37181518,37182376,58194643,71681839,71681842,71681845,71682767,119572054,684774527" 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/Q9BQB4" 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=50964" 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=ENSG00000167941;t=ENST00000301691" 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=SOST" 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=SOST" 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+50964" 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/SOST" 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:50964" 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/50964" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr17&hgg_gene=ENST00000301691.3&hgg_start=43753738&hgg_end=43758791&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:13771" 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://medlineplus.gov/genetics/gene/sost" 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=605740[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=605740[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000167941" 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.gwascentral.org/search?q=SOST" 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=SOST" 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="http://www.LOVD.nl/SOST" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=SOST&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/PA37809" 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:13771" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1921749" 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/SOST#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:1921749" 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/50964/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=50964" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-110411-139" 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:50964" 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=SOST&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 17568006<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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605740
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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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SCLEROSTIN; SOST
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<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=SOST" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">SOST</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/17/618?start=-3&limit=10&highlight=618">17q21.31</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr17:43753738-43758791&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">17:43,753,738-43,758,791</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="geneMap" class="mim-anchor"></a>
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<div style="margin-bottom: 10px;">
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<span class="h4 mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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<span class="hidden-sm hidden-xs pull-right">
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<a href="/clinicalSynopsis/table?mimNumber=122860,269500" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
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View Clinical Synopses
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</a>
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</span>
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="2">
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<span class="mim-font">
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<a href="/geneMap/17/618?start=-3&limit=10&highlight=618">
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17q21.31
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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Craniodiaphyseal dysplasia, autosomal dominant
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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/122860"> 122860 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Sclerosteosis 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/269500"> 269500 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
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</button>
|
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<ul class="dropdown-menu" style="width: 17em;">
|
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<li><a href="/graph/linear/605740" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
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<li><a href="/graph/radial/605740" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
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</div>
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|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></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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<a id="text" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
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<strong>TEXT</strong>
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</span>
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</span>
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</h4>
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<p>Sclerostin and noggin (NOG; <a href="/entry/602991">602991</a>) are bone morphogenic protein (BMP) antagonists that modulate mitogenic activity through sequestering BMPs (<a href="#15" class="mim-tip-reference" title="Winkler, D. G., Yu, C., Geoghegan, J. C., Ojala, E. W., Skonier, J. E., Shpektor, D., Sutherland, M. K., Latham, J. A. <strong>Noggin and sclerostin bone morphogenetic protein antagonists form a mutually inhibitory complex.</strong> J. Biol. Chem. 279: 36293-36298, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15199066/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15199066</a>] [<a href="https://doi.org/10.1074/jbc.M400521200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15199066">Winkler et al., 2004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15199066" 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>Through homozygosity mapping followed by positional cloning in Afrikaner families with sclerosteosis (<a href="/entry/269500">269500</a>), <a href="#4" class="mim-tip-reference" title="Brunkow, M. E., Gardner, J. C., Van Ness, J., Paeper, B. W., Kovacevich, B. R., Proll, S., Skonier, J. E., Zhao, L., Sabo, P. J., Fu, Y.-H., Alisch, R. S., Gillett, L., Colbert, T., Tacconi, P., Galas, D., Hamersma, H., Beighton, P., Mulligan, J. T. <strong>Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein.</strong> Am. J. Hum. Genet. 68: 577-589, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11179006/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11179006</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11179006[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/10.1086/318811" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11179006">Brunkow et al. (2001)</a> found 2 independent mutations in a novel gene, which they termed SOST. The SOST gene encodes a deduced 213-amino acid protein, sclerostin, that shares 89% and 88% sequence identity with the rat and mouse homologs. The protein contains a putative secretion signal and 2 N-glycosylation sites. It also contains a cystine knot motif (residues 80-167) with high similarity to the dan family of secreted glycoproteins, including dan (<a href="/entry/600613">600613</a>), cerberus (<a href="/entry/603777">603777</a>), gremlin (<a href="/entry/603054">603054</a>), and caronte (<a href="/entry/604172">604172</a>), which have been shown to act as antagonists of members of the transforming growth factor-beta superfamily (see <a href="/entry/190180">190180</a>). Quantitative RT-PCR showed relatively low overall expression of SOST, but significant expression in whole long bone, cartilage, kidney, and liver and lower expression in placenta and fetal skin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11179006" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Balemans, W., Ebeling, M., Patel, N., Van Hul, E., Olson, P., Dioszegi, M., Lacza, C., Wuyts, W., Van Den Ende, J., Willems, P., Paes-Alves, A. F., Hill, S., and 9 others. <strong>Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST).</strong> Hum. Molec. Genet. 10: 537-543, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11181578/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11181578</a>] [<a href="https://doi.org/10.1093/hmg/10.5.537" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11181578">Balemans et al. (2001)</a> independently isolated the SOST gene. Quantitative RT-PCR experiments revealed highest tissue expression in human kidney, followed by bone marrow and osteoblasts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11181578" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using in situ hybridization, <a href="#7" class="mim-tip-reference" title="Kusu, N., Laurikkala, J., Imanishi, M., Usui, H., Konishi, M., Miyake, A., Thesleff, I., Itoh, N. <strong>Sclerostin is a novel secreted osteoclast-derived bone morphogenetic protein antagonist with unique ligand specificity.</strong> J. Biol. Chem. 278: 24113-24117, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12702725/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12702725</a>] [<a href="https://doi.org/10.1074/jbc.M301716200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12702725">Kusu et al. (2003)</a> found that Sost was intensely expressed in developing bones of developing mouse embryos. Punctate expression of Sost was localized on the surface of both intramembranously forming skull bones and endochondrally forming long bones. Sost colocalized with Mmp9 (<a href="/entry/120361">120361</a>), an osteoclast marker. Recombinant Sost expressed in insect cells was secreted as a monomer. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12702725" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By RT-PCR, <a href="#14" class="mim-tip-reference" title="Winkler, D. G., Sutherland, M. K., Geoghegan, J. C., Yu, C., Hayes, T., Skonier, J. E., Shpektor, D., Jonas, M., Kovacevich, B. R., Staehling-Hampton, K., Appleby, M., Brunkow, M. E., Latham, J. A. <strong>Osteocyte control of bone formation via sclerostin, a novel BMP antagonist.</strong> EMBO J. 22: 6267-6276, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14633986/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14633986</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14633986[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/emboj/cdg599" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14633986">Winkler et al. (2003)</a> found human sclerostin expressed in primary human osteoblasts, mesenchymal cells differentiated in culture to osteoblasts, and hypertrophic chondrocytes in cartilage tissue. It was not expressed in adipocytes or adipose tissue. Immunohistochemical analysis of human bone detected expression in osteocytes and osteocytic canaliculi and/or cell processes in both cortical and trabecular bone. Staining was also observed in chondrocytes and weakly in other osteoblastic cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14633986" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The SOST gene contains 2 exons (<a href="#4" class="mim-tip-reference" title="Brunkow, M. E., Gardner, J. C., Van Ness, J., Paeper, B. W., Kovacevich, B. R., Proll, S., Skonier, J. E., Zhao, L., Sabo, P. J., Fu, Y.-H., Alisch, R. S., Gillett, L., Colbert, T., Tacconi, P., Galas, D., Hamersma, H., Beighton, P., Mulligan, J. T. <strong>Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein.</strong> Am. J. Hum. Genet. 68: 577-589, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11179006/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11179006</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11179006[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/10.1086/318811" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11179006">Brunkow et al., 2001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11179006" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The SOST gene maps to chromosome 17q12-q21 (<a href="#4" class="mim-tip-reference" title="Brunkow, M. E., Gardner, J. C., Van Ness, J., Paeper, B. W., Kovacevich, B. R., Proll, S., Skonier, J. E., Zhao, L., Sabo, P. J., Fu, Y.-H., Alisch, R. S., Gillett, L., Colbert, T., Tacconi, P., Galas, D., Hamersma, H., Beighton, P., Mulligan, J. T. <strong>Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein.</strong> Am. J. Hum. Genet. 68: 577-589, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11179006/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11179006</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11179006[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/10.1086/318811" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11179006">Brunkow et al., 2001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11179006" 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="#5" class="mim-tip-reference" title="Gross, M. B. <strong>Personal Communication.</strong> Baltimore, Md. 4/14/2014."None>Gross (2014)</a> mapped the SOST gene to chromosome 17q21.31 based on an alignment of the SOST sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=AF326736" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">AF326736</a>) with the genomic sequence (GRCh37).</p>
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<p><a href="#7" class="mim-tip-reference" title="Kusu, N., Laurikkala, J., Imanishi, M., Usui, H., Konishi, M., Miyake, A., Thesleff, I., Itoh, N. <strong>Sclerostin is a novel secreted osteoclast-derived bone morphogenetic protein antagonist with unique ligand specificity.</strong> J. Biol. Chem. 278: 24113-24117, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12702725/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12702725</a>] [<a href="https://doi.org/10.1074/jbc.M301716200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12702725">Kusu et al. (2003)</a> coexpressed mouse Sost with several human BMP cDNAs in a mouse preosteoblastic cell line and found that Sost inhibited differentiation stimulated by BMP6 (<a href="/entry/112266">112266</a>) and BMP7 (<a href="/entry/112267">112267</a>), but not BMP2 (<a href="/entry/112261">112261</a>) and BMP4 (<a href="/entry/112262">112262</a>). Sost bound BMP6 and BMP7 with high affinity and BMP2 and BMP4 with lower affinity. <a href="#7" class="mim-tip-reference" title="Kusu, N., Laurikkala, J., Imanishi, M., Usui, H., Konishi, M., Miyake, A., Thesleff, I., Itoh, N. <strong>Sclerostin is a novel secreted osteoclast-derived bone morphogenetic protein antagonist with unique ligand specificity.</strong> J. Biol. Chem. 278: 24113-24117, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12702725/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12702725</a>] [<a href="https://doi.org/10.1074/jbc.M301716200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12702725">Kusu et al. (2003)</a> concluded that SOST is a secreted osteoclast-derived BMP antagonist that represses BMP-induced osteoblast differentiation and/or function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12702725" 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="#14" class="mim-tip-reference" title="Winkler, D. G., Sutherland, M. K., Geoghegan, J. C., Yu, C., Hayes, T., Skonier, J. E., Shpektor, D., Jonas, M., Kovacevich, B. R., Staehling-Hampton, K., Appleby, M., Brunkow, M. E., Latham, J. A. <strong>Osteocyte control of bone formation via sclerostin, a novel BMP antagonist.</strong> EMBO J. 22: 6267-6276, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14633986/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14633986</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14633986[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/emboj/cdg599" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14633986">Winkler et al. (2003)</a> found that recombinant human sclerostin bound BMP2, BMP4, BMP5 (<a href="/entry/112265">112265</a>), BMP6, and BMP7 in vitro with similar binding kinetics and affinities. Competition studies indicated that the BMP proteins competed for the same site on sclerostin. Sclerostin binding to BMP6 competed with BMP6 binding to type I and type II BMP receptors (see <a href="/entry/601299">601299</a> and <a href="/entry/600799">600799</a>, respectively) and with the BMP antagonist DAN. Preincubation of sclerostin with human BMP6 partially blocked phosphorylation of SMADs (see SMAD1; <a href="/entry/601595">601595</a>) by BMP6 in mouse mesenchymal cells. Sclerostin reduced expression of genes associated with osteoblast differentiation and reduced proliferation of, and mineral deposition by, differentiated human mesenchymal cells and primary human osteoblasts in a dose-dependent manner. Overexpression of human SOST in transgenic mice resulted in a marked decrease in osteoblast activity and decreased bone formation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14633986" 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="#15" class="mim-tip-reference" title="Winkler, D. G., Yu, C., Geoghegan, J. C., Ojala, E. W., Skonier, J. E., Shpektor, D., Sutherland, M. K., Latham, J. A. <strong>Noggin and sclerostin bone morphogenetic protein antagonists form a mutually inhibitory complex.</strong> J. Biol. Chem. 279: 36293-36298, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15199066/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15199066</a>] [<a href="https://doi.org/10.1074/jbc.M400521200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15199066">Winkler et al. (2004)</a> found that human sclerostin interacted directly with noggin in vitro. The sclerostin-noggin interaction neutralized the ability of either protein to bind and inhibit BMP6, permitting BMP6 mitogenic activity in a mouse osteosarcoma cell line. Immunoprecipitation of sclerostin from a rat osteosarcoma cell line indicated that endogenous rat sclerostin forms a complex with Bmp2, Bmp5, and noggin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15199066" 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="Semenov, M., Tamai, K., He, X. <strong>SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor.</strong> J. Biol. Chem. 280: 26770-26775, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15908424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15908424</a>] [<a href="https://doi.org/10.1074/jbc.M504308200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15908424">Semenov et al. (2005)</a> found that human SOST antagonized Wnt (see <a href="/entry/606359">606359</a>) signaling in Xenopus embryos and mammalian cells by binding to the extracellular domains of the Wnt coreceptors Lrp5 (<a href="/entry/603506">603506</a>) and Lrp6 (<a href="/entry/603507">603507</a>) and disrupting Wnt-induced frizzled (see <a href="/entry/603408">603408</a>)-Lrp complex formation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15908424" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using tandem affinity purification and mass spectrometry of proteins isolated from HEK293 and rat UMR-106 osteoblastic cells, <a href="#8" class="mim-tip-reference" title="Leupin, O., Piters, E., Halleux, C., Hu, S., Kramer, I., Morvan, F., Bouwmeester, T., Schirle, M., Bueno-Lozano, M., Ramos Fuentes, F. J., Itin, P. H., Boudin, E., and 10 others. <strong>Bone overgrowth-associated mutations in the LRP4 gene impair sclerostin facilitator function.</strong> J. Biol. Chem. 286: 19489-19500, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21471202/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21471202</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21471202[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1074/jbc.M110.190330" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21471202">Leupin et al. (2011)</a> found that sclerostin interacted with LRP4 (<a href="/entry/604270">604270</a>), LRP5, and LRP6. ELISA experiments confirmed a dose-dependent interaction between recombinant LRP4 and sclerostin. Mutation analysis revealed that membrane localization mediated by the beta-propeller domain of LRP4 was required for the interaction. Overexpression of LRP4 in HEK293 cells or C28a2 human chondrocytes enhanced sclerostin-mediated inhibition of WNT1 (<a href="/entry/164820">164820</a>) signaling, whereas knockdown of LRP4 mRNA in HEK293 cells via RNA interference reduced sclerostin- but not DKK1 (<a href="/entry/605189">605189</a>)-mediated inhibition of WNT signaling. Knockdown of Lrp4 significantly blocked sclerostin inhibition of bone mineralization in mouse bone marrow stromal cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21471202" 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>Sclerosteosis 1</em></strong></p><p>
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In Afrikaners with sclerosteosis (SOST1; <a href="/entry/269500">269500</a>), <a href="#4" class="mim-tip-reference" title="Brunkow, M. E., Gardner, J. C., Van Ness, J., Paeper, B. W., Kovacevich, B. R., Proll, S., Skonier, J. E., Zhao, L., Sabo, P. J., Fu, Y.-H., Alisch, R. S., Gillett, L., Colbert, T., Tacconi, P., Galas, D., Hamersma, H., Beighton, P., Mulligan, J. T. <strong>Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein.</strong> Am. J. Hum. Genet. 68: 577-589, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11179006/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11179006</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11179006[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/10.1086/318811" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11179006">Brunkow et al. (2001)</a> found homozygosity for a nonsense mutation in the N terminus of sclerostin (<a href="#0001">605740.0001</a>). In an unrelated affected person of Senegalese origin reported by <a href="#11" class="mim-tip-reference" title="Tacconi, P., Ferrigno, P., Cocco, L., Cannas, A., Tamburini, G., Bergonzi, P., Giagheddu, M. <strong>Sclerosteosis: report of a case in a black African man.</strong> Clin. Genet. 53: 497-501, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9712543/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9712543</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1998.tb02603.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9712543">Tacconi et al. (1998)</a>, they found homozygosity for a splice mutation within the single intron of the SOST gene (<a href="#0002">605740.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9712543+11179006" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Balemans, W., Ebeling, M., Patel, N., Van Hul, E., Olson, P., Dioszegi, M., Lacza, C., Wuyts, W., Van Den Ende, J., Willems, P., Paes-Alves, A. F., Hill, S., and 9 others. <strong>Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST).</strong> Hum. Molec. Genet. 10: 537-543, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11181578/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11181578</a>] [<a href="https://doi.org/10.1093/hmg/10.5.537" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11181578">Balemans et al. (2001)</a> described 2 families with sclerosteosis harboring homozygous mutations in the SOST gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11181578" 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>Van Buchem Disease</em></strong></p><p>
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<a href="#4" class="mim-tip-reference" title="Brunkow, M. E., Gardner, J. C., Van Ness, J., Paeper, B. W., Kovacevich, B. R., Proll, S., Skonier, J. E., Zhao, L., Sabo, P. J., Fu, Y.-H., Alisch, R. S., Gillett, L., Colbert, T., Tacconi, P., Galas, D., Hamersma, H., Beighton, P., Mulligan, J. T. <strong>Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein.</strong> Am. J. Hum. Genet. 68: 577-589, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11179006/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11179006</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11179006[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/10.1086/318811" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11179006">Brunkow et al. (2001)</a> analyzed the SOST gene in 7 Dutch patients with van Buchem disease (VBCH; <a href="/entry/239100">239100</a>) and detected no mutations in the coding region. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11179006" 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 affected members from a large consanguineous Dutch family with van Buchem disease studied by <a href="#13" class="mim-tip-reference" title="Van Hul, W., Balemans, W., Van Hul, E., Dikkers, F. G., Obee, H., Stokroos, R. J., Hildering, P., Vanhoenacker, F., Van Camp, G., Willems, P. J. <strong>Van Buchem disease (hyperostosis corticalis generalisata) maps to chromosome 17q12-q21.</strong> Am. J. Hum. Genet. 62: 391-399, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9463328/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9463328</a>] [<a href="https://doi.org/10.1086/301721" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9463328">Van Hul et al. (1998)</a>, <a href="#2" class="mim-tip-reference" title="Balemans, W., Patel, N., Ebeling, M., Van Hul, E., Wuyts, W., Lacza, C., Dioszegi, M., Dikkers, F. G., Hildering, P., Willems, P. J., Verheij, J. B. G. M., Lindpaintner, K., Vickery, B., Foernzler, D., Van Hul, W. <strong>Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease.</strong> J. Med. Genet. 39: 91-97, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11836356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11836356</a>] [<a href="https://doi.org/10.1136/jmg.39.2.91" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11836356">Balemans et al. (2002)</a> identified a homozygous 52-kb deletion approximately 35 kb downstream of the SOST gene. Three additional Dutch patients with van Buchem disease also had the deletion. The parents of affected individuals were heterozygous for the deletion. Analysis of the sequences flanking the deletion breakpoints showed the presence of Alu repeats on either side, suggesting an Alu-mediated, unequal homologous recombination event as the mechanism causing the deletion. As no coding sequences could be identified within the deleted region, <a href="#2" class="mim-tip-reference" title="Balemans, W., Patel, N., Ebeling, M., Van Hul, E., Wuyts, W., Lacza, C., Dioszegi, M., Dikkers, F. G., Hildering, P., Willems, P. J., Verheij, J. B. G. M., Lindpaintner, K., Vickery, B., Foernzler, D., Van Hul, W. <strong>Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease.</strong> J. Med. Genet. 39: 91-97, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11836356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11836356</a>] [<a href="https://doi.org/10.1136/jmg.39.2.91" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11836356">Balemans et al. (2002)</a> suggested that the deletion may alter transcription of the SOST gene in patients with van Buchem disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9463328+11836356" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using transgenic mice, <a href="#9" class="mim-tip-reference" title="Loots, G. G., Kneissel, M., Keller, H., Baptist, M., Chang, J., Collette, N. M., Ovcharenko, D., Plajzer-Frick, I., Rubin, E. M. <strong>Genomic deletion of a long-range bone enhancer misregulates sclerostin in Van Buchem disease.</strong> Genome Res. 15: 928-935, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15965026/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15965026</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15965026[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/10.1101/gr.3437105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15965026">Loots et al. (2005)</a> characterized expression of human SOST from the wildtype allele and an allele carrying the van Buchem disease-associated 52-kb noncoding deletion downstream of SOST (VB allele). Transgenic mice with the wildtype allele expressed human SOST by embryonic day 9.5, predominantly in mesenchymal tissue of the developing limb bud, and adult transgenic mice expressed SOST in bone, kidney, and heart. These mice grew to skeletal maturity with normal body size and weight, but they displayed decreased bone mineral density. In contrast, transgenic mice expressing the VB allele did not express SOST in adult bone, and their bone parameters were indistinguishable from nontransgenic littermates. The numbers of osteocytes and osteoclasts were not significantly affected by transgenic expression, but elevated levels of SOST in transgenic mice with either allele resulted in a wide range of fused and missing digits in forelimbs and hindlimbs. <a href="#9" class="mim-tip-reference" title="Loots, G. G., Kneissel, M., Keller, H., Baptist, M., Chang, J., Collette, N. M., Ovcharenko, D., Plajzer-Frick, I., Rubin, E. M. <strong>Genomic deletion of a long-range bone enhancer misregulates sclerostin in Van Buchem disease.</strong> Genome Res. 15: 928-935, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15965026/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15965026</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15965026[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/10.1101/gr.3437105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15965026">Loots et al. (2005)</a> identified 7 evolutionarily conserved regions (ECRs) within the van Buchem disease-associated deletion. They examined skeletal structures of transgenic mouse embryos expressing each of these human ECRs and found that the 250-bp ECR5 enhanced SOST expression in cartilage of ribs, vertebrae, and skull plates. ECR5 was also capable of activating the human SOST promoter in osteoblast-like cell lines. <a href="#9" class="mim-tip-reference" title="Loots, G. G., Kneissel, M., Keller, H., Baptist, M., Chang, J., Collette, N. M., Ovcharenko, D., Plajzer-Frick, I., Rubin, E. M. <strong>Genomic deletion of a long-range bone enhancer misregulates sclerostin in Van Buchem disease.</strong> Genome Res. 15: 928-935, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15965026/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15965026</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15965026[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/10.1101/gr.3437105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15965026">Loots et al. (2005)</a> concluded that van Buchem disease is caused by deletion of a SOST-specific regulatory element and is allelic to sclerosteosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15965026" 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>Craniodiaphyseal Dysplasia, Autosomal Dominant</em></strong></p><p>
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In a Korean girl with autosomal dominant craniodiaphyseal dysplasia (CDD; <a href="/entry/122860">122860</a>), <a href="#6" class="mim-tip-reference" title="Kim, S. J., Bieganski, T., Sohn, Y. B., Kozlowski, K., Semenov, M., Okamoto, N., Kim, C. H., Ko, A.-R., Ahn, G. H., Choi, Y.-L., Park, S. W., Ki, C.-S., Kim, O.-H., Nishimura, G., Unger, S., Superti-Furga, A., Jin, D.-K. <strong>Identification of signal peptide domain SOST mutations in autosomal dominant craniodiaphyseal dysplasia.</strong> Hum. Genet. 129: 497-502, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21221996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21221996</a>] [<a href="https://doi.org/10.1007/s00439-011-0947-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21221996">Kim et al. (2011)</a> identified a de novo heterozygous mutation in the SOST gene (V21M; <a href="#0005">605740.0005</a>). Genetic analysis of an affected patient reported by <a href="#3" class="mim-tip-reference" title="Bieganski, T., Baranska, D., Miastkowska, I., Kobielski, A., Gorska-Chrzastek, M., Kozlowski, K. <strong>A boy with severe craniodiaphyseal dysplasia and apparently normal mother.</strong> Am. J. Med. Genet. 143A: 2435-2443, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17853455/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17853455</a>] [<a href="https://doi.org/10.1002/ajmg.a.31938" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17853455">Bieganski et al. (2007)</a> identified a second heterozygous SOST mutation affecting the same residue (V21L; <a href="#0006">605740.0006</a>). DNA from the possibly affected mother of the second patient was not available. Both mutations affected the secretion signal peptide of the protein, and in vitro functional expression studies showed that the mutations resulted in significantly decreased SOST secretion, although the proteins were produced in the cells. <a href="#6" class="mim-tip-reference" title="Kim, S. J., Bieganski, T., Sohn, Y. B., Kozlowski, K., Semenov, M., Okamoto, N., Kim, C. H., Ko, A.-R., Ahn, G. H., Choi, Y.-L., Park, S. W., Ki, C.-S., Kim, O.-H., Nishimura, G., Unger, S., Superti-Furga, A., Jin, D.-K. <strong>Identification of signal peptide domain SOST mutations in autosomal dominant craniodiaphyseal dysplasia.</strong> Hum. Genet. 129: 497-502, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21221996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21221996</a>] [<a href="https://doi.org/10.1007/s00439-011-0947-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21221996">Kim et al. (2011)</a> noted the phenotypic differences from other disorders due to SOST mutations, which are less severe and transmitted in an autosomal recessive pattern, and postulated a dominant-negative mechanism in CDD. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17853455+21221996" 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>SOST Polymorphisms Associated with Bone Mineral Density</em></strong></p><p>
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<a href="#12" class="mim-tip-reference" title="Uitterlinden, A. G., Arp, P. P., Paeper, B. W., Charmley, P., Proll, S., Rivadeneira, F., Fang, Y., van Meurs, J. B. J., Britschgi, T. B., Latham, J. A., Schatzman, R. C., Pols, H. A. P., Brunkow, M. E. <strong>Polymorphisms in the sclerosteosis/van Buchem disease gene (SOST) region are associated with bone-mineral density in elderly whites.</strong> Am. J. Hum. Genet. 75: 1032-1045, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15514891/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15514891</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15514891[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/10.1086/426458" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15514891">Uitterlinden et al. (2004)</a> studied whether the SOST gene is an osteoporosis risk gene by examining its association with bone mineral density (BMD). They used a set of 8 polymorphisms from the SOST region to genotype 1,939 elderly men and women from a large population-based prospective cohort study of Dutch whites. They found that a 3-bp insertion in the presumed SOST promoter region, with a gene frequency of 0.38, was associated with decreased BMD in women at the femoral neck and lumbar spine, with evidence of an allele dosage effect in the oldest age group. Similarly, a G variant in the van Buchem deletion region (gene frequency = 0.40) was associated with increased BMD in men at the femoral neck and lumbar spine. In both cases, differences between extreme genotypes reached 0.2 standard deviations. No genotype effects on fracture risk were observed for the 234 osteoporotic fractures validated during 8.2 years of follow-up and for the 146 vertebral prevalent fractures analyzed. <a href="#12" class="mim-tip-reference" title="Uitterlinden, A. G., Arp, P. P., Paeper, B. W., Charmley, P., Proll, S., Rivadeneira, F., Fang, Y., van Meurs, J. B. J., Britschgi, T. B., Latham, J. A., Schatzman, R. C., Pols, H. A. P., Brunkow, M. E. <strong>Polymorphisms in the sclerosteosis/van Buchem disease gene (SOST) region are associated with bone-mineral density in elderly whites.</strong> Am. J. Hum. Genet. 75: 1032-1045, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15514891/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15514891</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15514891[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/10.1086/426458" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15514891">Uitterlinden et al. (2004)</a> found evidence of additive effects of the insertion polymorphism with the Sp1-binding site polymorphism of the COL1A1 gene (<a href="/entry/120150#0051">120150.0051</a>). They suggested that the moderate SOST genotype effects involved differences in regulation of SOST gene expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15514891" 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="mimAllelicVariantsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>6 Selected Examples</a>):</strong>
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<a href="/allelicVariants/605740" class="btn btn-default" role="button"> Table View </a>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=605740[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906320 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906320;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=rs387906320" 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=rs387906320" 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=RCV000005049 OR RCV005089173" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005049, RCV005089173" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005049...</a>
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<p>In Afrikaners with sclerosteosis (SOST1; <a href="/entry/269500">269500</a>), <a href="#4" class="mim-tip-reference" title="Brunkow, M. E., Gardner, J. C., Van Ness, J., Paeper, B. W., Kovacevich, B. R., Proll, S., Skonier, J. E., Zhao, L., Sabo, P. J., Fu, Y.-H., Alisch, R. S., Gillett, L., Colbert, T., Tacconi, P., Galas, D., Hamersma, H., Beighton, P., Mulligan, J. T. <strong>Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein.</strong> Am. J. Hum. Genet. 68: 577-589, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11179006/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11179006</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11179006[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/10.1086/318811" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11179006">Brunkow et al. (2001)</a> identified a homozygous C-to-T substitution located 69 bp downstream of the predicted translation initiation site of the SOST gene, resulting in termination of translation 23 residues from the N terminus. The mutation was not found in over 400 controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11179006" 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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SOST, IVS1DS, A-T, +3 AND/OR IVS1AS, A-C, -67
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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> rs114609105 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs114609105;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/rs114609105?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=rs114609105" 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=rs114609105" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div> <div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2154590472 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2154590472;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=rs2154590472" 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=rs2154590472" 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=RCV000005050 OR RCV001843427" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005050, RCV001843427" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005050...</a>
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<p>In a Senegalese patient with sclerosteosis (SOST1; <a href="/entry/269500">269500</a>) reported by <a href="#11" class="mim-tip-reference" title="Tacconi, P., Ferrigno, P., Cocco, L., Cannas, A., Tamburini, G., Bergonzi, P., Giagheddu, M. <strong>Sclerosteosis: report of a case in a black African man.</strong> Clin. Genet. 53: 497-501, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9712543/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9712543</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1998.tb02603.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9712543">Tacconi et al. (1998)</a>, <a href="#4" class="mim-tip-reference" title="Brunkow, M. E., Gardner, J. C., Van Ness, J., Paeper, B. W., Kovacevich, B. R., Proll, S., Skonier, J. E., Zhao, L., Sabo, P. J., Fu, Y.-H., Alisch, R. S., Gillett, L., Colbert, T., Tacconi, P., Galas, D., Hamersma, H., Beighton, P., Mulligan, J. T. <strong>Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein.</strong> Am. J. Hum. Genet. 68: 577-589, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11179006/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11179006</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11179006[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/10.1086/318811" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11179006">Brunkow et al. (2001)</a> found 2 homozygous changes in the single intron of the SOST gene. Since neither of these nucleotide differences existed in the sequence of 360 unaffected control DNAs, they concluded that one or both of them could have a deleterious effect on splicing of the mRNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9712543+11179006" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 SCLEROSTEOSIS 1</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894644 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894644;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=rs104894644" 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=rs104894644" 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=RCV000005051" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005051" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005051</a>
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<p>In a Brazilian family with sclerosteosis (SOST1; <a href="/entry/269500">269500</a>), <a href="#1" class="mim-tip-reference" title="Balemans, W., Ebeling, M., Patel, N., Van Hul, E., Olson, P., Dioszegi, M., Lacza, C., Wuyts, W., Van Den Ende, J., Willems, P., Paes-Alves, A. F., Hill, S., and 9 others. <strong>Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST).</strong> Hum. Molec. Genet. 10: 537-543, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11181578/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11181578</a>] [<a href="https://doi.org/10.1093/hmg/10.5.537" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11181578">Balemans et al. (2001)</a> identified a homozygous 372G-A transition in exon 2 of the SOST gene, resulting in a trp124-to-ter nonsense mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11181578" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 SCLEROSTEOSIS 1</strong>
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SOST, ARG126TER
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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> rs104894645 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894645;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/rs104894645?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=rs104894645" 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=rs104894645" 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=RCV000005052" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005052" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005052</a>
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<p>In an American family with sclerosteosis (SOST1; <a href="/entry/269500">269500</a>), <a href="#1" class="mim-tip-reference" title="Balemans, W., Ebeling, M., Patel, N., Van Hul, E., Olson, P., Dioszegi, M., Lacza, C., Wuyts, W., Van Den Ende, J., Willems, P., Paes-Alves, A. F., Hill, S., and 9 others. <strong>Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST).</strong> Hum. Molec. Genet. 10: 537-543, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11181578/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11181578</a>] [<a href="https://doi.org/10.1093/hmg/10.5.537" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11181578">Balemans et al. (2001)</a> found a homozygous 376C-T transition in exon 2 of the SOST gene, resulting in an arg126-to-ter nonsense mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11181578" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 CRANIODIAPHYSEAL DYSPLASIA, AUTOSOMAL DOMINANT</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387907169 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387907169;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=rs387907169" 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=rs387907169" 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=RCV000024297 OR RCV003398567" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000024297, RCV003398567" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000024297...</a>
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<p>In a Korean girl with autosomal dominant craniodiaphyseal dysplasia (CDD; <a href="/entry/122860">122860</a>), <a href="#6" class="mim-tip-reference" title="Kim, S. J., Bieganski, T., Sohn, Y. B., Kozlowski, K., Semenov, M., Okamoto, N., Kim, C. H., Ko, A.-R., Ahn, G. H., Choi, Y.-L., Park, S. W., Ki, C.-S., Kim, O.-H., Nishimura, G., Unger, S., Superti-Furga, A., Jin, D.-K. <strong>Identification of signal peptide domain SOST mutations in autosomal dominant craniodiaphyseal dysplasia.</strong> Hum. Genet. 129: 497-502, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21221996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21221996</a>] [<a href="https://doi.org/10.1007/s00439-011-0947-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21221996">Kim et al. (2011)</a> identified a de novo heterozygous 61G-A transition in the SOST gene, resulting in a val21-to-met (V21M) substitution in the secretion signal of the protein. In a second patient, <a href="#6" class="mim-tip-reference" title="Kim, S. J., Bieganski, T., Sohn, Y. B., Kozlowski, K., Semenov, M., Okamoto, N., Kim, C. H., Ko, A.-R., Ahn, G. H., Choi, Y.-L., Park, S. W., Ki, C.-S., Kim, O.-H., Nishimura, G., Unger, S., Superti-Furga, A., Jin, D.-K. <strong>Identification of signal peptide domain SOST mutations in autosomal dominant craniodiaphyseal dysplasia.</strong> Hum. Genet. 129: 497-502, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21221996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21221996</a>] [<a href="https://doi.org/10.1007/s00439-011-0947-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21221996">Kim et al. (2011)</a> identified a different mutation affecting the same residue (V21L; <a href="#0006">605740.0006</a>). In vitro functional expression studies showed that the mutations resulted in significantly decreased SOST secretion, although the proteins were produced in the cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21221996" 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">rs387907169 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387907169;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=rs387907169" 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=rs387907169" 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=RCV000024298" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000024298" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000024298</a>
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<p>In a patient with autosomal dominant craniodiaphyseal dysplasia (CDD; <a href="/entry/122860">122860</a>), originally reported by <a href="#3" class="mim-tip-reference" title="Bieganski, T., Baranska, D., Miastkowska, I., Kobielski, A., Gorska-Chrzastek, M., Kozlowski, K. <strong>A boy with severe craniodiaphyseal dysplasia and apparently normal mother.</strong> Am. J. Med. Genet. 143A: 2435-2443, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17853455/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17853455</a>] [<a href="https://doi.org/10.1002/ajmg.a.31938" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17853455">Bieganski et al. (2007)</a>, <a href="#6" class="mim-tip-reference" title="Kim, S. J., Bieganski, T., Sohn, Y. B., Kozlowski, K., Semenov, M., Okamoto, N., Kim, C. H., Ko, A.-R., Ahn, G. H., Choi, Y.-L., Park, S. W., Ki, C.-S., Kim, O.-H., Nishimura, G., Unger, S., Superti-Furga, A., Jin, D.-K. <strong>Identification of signal peptide domain SOST mutations in autosomal dominant craniodiaphyseal dysplasia.</strong> Hum. Genet. 129: 497-502, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21221996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21221996</a>] [<a href="https://doi.org/10.1007/s00439-011-0947-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21221996">Kim et al. (2011)</a> identified a heterozygous 61G-T transversion in the SOST gene, resulting in a val21-to-leu (V21L) substitution in the secretion signal of the protein. DNA from his possibly affected mother was not available. An unrelated patient with the disorder had a mutation affecting the same residue (V21M; <a href="#0005">605740.0005</a>). In vitro functional expression studies showed that both mutations resulted in significantly decreased SOST secretion, although the proteins were produced in the cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17853455+21221996" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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Balemans, W., Ebeling, M., Patel, N., Van Hul, E., Olson, P., Dioszegi, M., Lacza, C., Wuyts, W., Van Den Ende, J., Willems, P., Paes-Alves, A. F., Hill, S., and 9 others.
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<strong>Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST).</strong>
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Hum. Molec. Genet. 10: 537-543, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11181578/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11181578</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11181578" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/10.5.537" target="_blank">Full Text</a>]
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Balemans, W., Patel, N., Ebeling, M., Van Hul, E., Wuyts, W., Lacza, C., Dioszegi, M., Dikkers, F. G., Hildering, P., Willems, P. J., Verheij, J. B. G. M., Lindpaintner, K., Vickery, B., Foernzler, D., Van Hul, W.
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<strong>Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease.</strong>
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J. Med. Genet. 39: 91-97, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11836356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11836356</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11836356" 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/10.1136/jmg.39.2.91" target="_blank">Full Text</a>]
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Bieganski, T., Baranska, D., Miastkowska, I., Kobielski, A., Gorska-Chrzastek, M., Kozlowski, K.
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<strong>A boy with severe craniodiaphyseal dysplasia and apparently normal mother.</strong>
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Am. J. Med. Genet. 143A: 2435-2443, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17853455/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17853455</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17853455" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.31938" target="_blank">Full Text</a>]
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Brunkow, M. E., Gardner, J. C., Van Ness, J., Paeper, B. W., Kovacevich, B. R., Proll, S., Skonier, J. E., Zhao, L., Sabo, P. J., Fu, Y.-H., Alisch, R. S., Gillett, L., Colbert, T., Tacconi, P., Galas, D., Hamersma, H., Beighton, P., Mulligan, J. T.
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<strong>Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein.</strong>
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Am. J. Hum. Genet. 68: 577-589, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11179006/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11179006</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11179006[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=11179006" 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/10.1086/318811" target="_blank">Full Text</a>]
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Gross, M. B.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 4/14/2014.
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Kim, S. J., Bieganski, T., Sohn, Y. B., Kozlowski, K., Semenov, M., Okamoto, N., Kim, C. H., Ko, A.-R., Ahn, G. H., Choi, Y.-L., Park, S. W., Ki, C.-S., Kim, O.-H., Nishimura, G., Unger, S., Superti-Furga, A., Jin, D.-K.
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<strong>Identification of signal peptide domain SOST mutations in autosomal dominant craniodiaphyseal dysplasia.</strong>
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Hum. Genet. 129: 497-502, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21221996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21221996</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21221996" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s00439-011-0947-3" target="_blank">Full Text</a>]
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Kusu, N., Laurikkala, J., Imanishi, M., Usui, H., Konishi, M., Miyake, A., Thesleff, I., Itoh, N.
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<strong>Sclerostin is a novel secreted osteoclast-derived bone morphogenetic protein antagonist with unique ligand specificity.</strong>
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J. Biol. Chem. 278: 24113-24117, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12702725/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12702725</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12702725" 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.M301716200" target="_blank">Full Text</a>]
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Leupin, O., Piters, E., Halleux, C., Hu, S., Kramer, I., Morvan, F., Bouwmeester, T., Schirle, M., Bueno-Lozano, M., Ramos Fuentes, F. J., Itin, P. H., Boudin, E., and 10 others.
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<strong>Bone overgrowth-associated mutations in the LRP4 gene impair sclerostin facilitator function.</strong>
|
|
J. Biol. Chem. 286: 19489-19500, 2011.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21471202/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21471202</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21471202[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=21471202" 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.M110.190330" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="9" class="mim-anchor"></a>
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<a id="Loots2005" class="mim-anchor"></a>
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|
<div class="">
|
|
<p class="mim-text-font">
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|
Loots, G. G., Kneissel, M., Keller, H., Baptist, M., Chang, J., Collette, N. M., Ovcharenko, D., Plajzer-Frick, I., Rubin, E. M.
|
|
<strong>Genomic deletion of a long-range bone enhancer misregulates sclerostin in Van Buchem disease.</strong>
|
|
Genome Res. 15: 928-935, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15965026/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15965026</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15965026[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=15965026" 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/10.1101/gr.3437105" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="10" class="mim-anchor"></a>
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<a id="Semenov2005" class="mim-anchor"></a>
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|
<div class="">
|
|
<p class="mim-text-font">
|
|
Semenov, M., Tamai, K., He, X.
|
|
<strong>SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor.</strong>
|
|
J. Biol. Chem. 280: 26770-26775, 2005.
|
|
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15908424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15908424</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15908424" 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.M504308200" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="11" class="mim-anchor"></a>
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<a id="Tacconi1998" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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|
Tacconi, P., Ferrigno, P., Cocco, L., Cannas, A., Tamburini, G., Bergonzi, P., Giagheddu, M.
|
|
<strong>Sclerosteosis: report of a case in a black African man.</strong>
|
|
Clin. Genet. 53: 497-501, 1998.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9712543/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9712543</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9712543" 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.1399-0004.1998.tb02603.x" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="12" class="mim-anchor"></a>
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<a id="Uitterlinden2004" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Uitterlinden, A. G., Arp, P. P., Paeper, B. W., Charmley, P., Proll, S., Rivadeneira, F., Fang, Y., van Meurs, J. B. J., Britschgi, T. B., Latham, J. A., Schatzman, R. C., Pols, H. A. P., Brunkow, M. E.
|
|
<strong>Polymorphisms in the sclerosteosis/van Buchem disease gene (SOST) region are associated with bone-mineral density in elderly whites.</strong>
|
|
Am. J. Hum. Genet. 75: 1032-1045, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15514891/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15514891</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15514891[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=15514891" 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/10.1086/426458" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="13" class="mim-anchor"></a>
|
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<a id="Van Hul1998" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Van Hul, W., Balemans, W., Van Hul, E., Dikkers, F. G., Obee, H., Stokroos, R. J., Hildering, P., Vanhoenacker, F., Van Camp, G., Willems, P. J.
|
|
<strong>Van Buchem disease (hyperostosis corticalis generalisata) maps to chromosome 17q12-q21.</strong>
|
|
Am. J. Hum. Genet. 62: 391-399, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9463328/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9463328</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9463328" 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/10.1086/301721" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="14" class="mim-anchor"></a>
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<a id="Winkler2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Winkler, D. G., Sutherland, M. K., Geoghegan, J. C., Yu, C., Hayes, T., Skonier, J. E., Shpektor, D., Jonas, M., Kovacevich, B. R., Staehling-Hampton, K., Appleby, M., Brunkow, M. E., Latham, J. A.
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<strong>Osteocyte control of bone formation via sclerostin, a novel BMP antagonist.</strong>
|
|
EMBO J. 22: 6267-6276, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14633986/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14633986</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14633986[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=14633986" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/emboj/cdg599" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="15" class="mim-anchor"></a>
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<a id="Winkler2004" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Winkler, D. G., Yu, C., Geoghegan, J. C., Ojala, E. W., Skonier, J. E., Shpektor, D., Sutherland, M. K., Latham, J. A.
|
|
<strong>Noggin and sclerostin bone morphogenetic protein antagonists form a mutually inhibitory complex.</strong>
|
|
J. Biol. Chem. 279: 36293-36298, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15199066/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15199066</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15199066" 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.M400521200" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
|
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
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Matthew B. Gross - updated : 04/14/2014
|
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</span>
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</div>
|
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</div>
|
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<div class="row collapse" id="mimCollapseContributors">
|
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 5/23/2012<br>Patricia A. Hartz - updated : 8/2/2011<br>Patricia A. Hartz - updated : 11/9/2005<br>Victor A. McKusick - updated : 11/11/2004<br>George E. Tiller - updated : 5/24/2001
|
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
|
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
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<span class="text-nowrap mim-text-font">
|
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Creation Date:
|
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</span>
|
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</div>
|
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
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Victor A. McKusick : 3/15/2001
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
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</span>
|
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</div>
|
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
|
carol : 01/17/2018
|
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</span>
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</div>
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</div>
|
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
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|
mgross : 04/14/2014<br>carol : 4/14/2014<br>carol : 2/26/2013<br>alopez : 5/24/2012<br>ckniffin : 5/23/2012<br>carol : 10/25/2011<br>mgross : 10/14/2011<br>terry : 8/2/2011<br>mgross : 12/1/2005<br>mgross : 12/1/2005<br>terry : 11/9/2005<br>tkritzer : 11/12/2004<br>terry : 11/11/2004<br>cwells : 5/25/2001<br>cwells : 5/24/2001<br>cwells : 5/23/2001<br>carol : 3/19/2001<br>terry : 3/16/2001<br>carol : 3/16/2001
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
|
|
<span class="mim-font">
|
|
<strong>*</strong> 605740
|
|
</span>
|
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</h3>
|
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</div>
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<div>
|
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<h3>
|
|
<span class="mim-font">
|
|
|
|
SCLEROSTIN; SOST
|
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: SOST</em></strong>
|
|
</span>
|
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</p>
|
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</div>
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<div>
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<p>
|
|
<span class="mim-text-font">
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|
|
|
<strong>SNOMEDCT:</strong> 17568006;
|
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 17q21.31
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 17:43,753,738-43,758,791 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
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</p>
|
|
</div>
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<div>
|
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<br />
|
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</div>
|
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
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</span>
|
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</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
17q21.31
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Craniodiaphyseal dysplasia, autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
122860
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
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|
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</tr>
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|
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|
|
|
|
|
|
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|
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<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Sclerosteosis 1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
269500
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
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</tbody>
|
|
</table>
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</div>
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</div>
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<div>
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<br />
|
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</div>
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<div>
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|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<span class="mim-text-font">
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<p>Sclerostin and noggin (NOG; 602991) are bone morphogenic protein (BMP) antagonists that modulate mitogenic activity through sequestering BMPs (Winkler et al., 2004). </p>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Through homozygosity mapping followed by positional cloning in Afrikaner families with sclerosteosis (269500), Brunkow et al. (2001) found 2 independent mutations in a novel gene, which they termed SOST. The SOST gene encodes a deduced 213-amino acid protein, sclerostin, that shares 89% and 88% sequence identity with the rat and mouse homologs. The protein contains a putative secretion signal and 2 N-glycosylation sites. It also contains a cystine knot motif (residues 80-167) with high similarity to the dan family of secreted glycoproteins, including dan (600613), cerberus (603777), gremlin (603054), and caronte (604172), which have been shown to act as antagonists of members of the transforming growth factor-beta superfamily (see 190180). Quantitative RT-PCR showed relatively low overall expression of SOST, but significant expression in whole long bone, cartilage, kidney, and liver and lower expression in placenta and fetal skin. </p><p>Balemans et al. (2001) independently isolated the SOST gene. Quantitative RT-PCR experiments revealed highest tissue expression in human kidney, followed by bone marrow and osteoblasts. </p><p>Using in situ hybridization, Kusu et al. (2003) found that Sost was intensely expressed in developing bones of developing mouse embryos. Punctate expression of Sost was localized on the surface of both intramembranously forming skull bones and endochondrally forming long bones. Sost colocalized with Mmp9 (120361), an osteoclast marker. Recombinant Sost expressed in insect cells was secreted as a monomer. </p><p>By RT-PCR, Winkler et al. (2003) found human sclerostin expressed in primary human osteoblasts, mesenchymal cells differentiated in culture to osteoblasts, and hypertrophic chondrocytes in cartilage tissue. It was not expressed in adipocytes or adipose tissue. Immunohistochemical analysis of human bone detected expression in osteocytes and osteocytic canaliculi and/or cell processes in both cortical and trabecular bone. Staining was also observed in chondrocytes and weakly in other osteoblastic cells. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The SOST gene contains 2 exons (Brunkow et al., 2001). </p>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The SOST gene maps to chromosome 17q12-q21 (Brunkow et al., 2001). </p><p>Gross (2014) mapped the SOST gene to chromosome 17q21.31 based on an alignment of the SOST sequence (GenBank AF326736) with the genomic sequence (GRCh37).</p>
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</span>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Kusu et al. (2003) coexpressed mouse Sost with several human BMP cDNAs in a mouse preosteoblastic cell line and found that Sost inhibited differentiation stimulated by BMP6 (112266) and BMP7 (112267), but not BMP2 (112261) and BMP4 (112262). Sost bound BMP6 and BMP7 with high affinity and BMP2 and BMP4 with lower affinity. Kusu et al. (2003) concluded that SOST is a secreted osteoclast-derived BMP antagonist that represses BMP-induced osteoblast differentiation and/or function. </p><p>Winkler et al. (2003) found that recombinant human sclerostin bound BMP2, BMP4, BMP5 (112265), BMP6, and BMP7 in vitro with similar binding kinetics and affinities. Competition studies indicated that the BMP proteins competed for the same site on sclerostin. Sclerostin binding to BMP6 competed with BMP6 binding to type I and type II BMP receptors (see 601299 and 600799, respectively) and with the BMP antagonist DAN. Preincubation of sclerostin with human BMP6 partially blocked phosphorylation of SMADs (see SMAD1; 601595) by BMP6 in mouse mesenchymal cells. Sclerostin reduced expression of genes associated with osteoblast differentiation and reduced proliferation of, and mineral deposition by, differentiated human mesenchymal cells and primary human osteoblasts in a dose-dependent manner. Overexpression of human SOST in transgenic mice resulted in a marked decrease in osteoblast activity and decreased bone formation. </p><p>Winkler et al. (2004) found that human sclerostin interacted directly with noggin in vitro. The sclerostin-noggin interaction neutralized the ability of either protein to bind and inhibit BMP6, permitting BMP6 mitogenic activity in a mouse osteosarcoma cell line. Immunoprecipitation of sclerostin from a rat osteosarcoma cell line indicated that endogenous rat sclerostin forms a complex with Bmp2, Bmp5, and noggin. </p><p>Semenov et al. (2005) found that human SOST antagonized Wnt (see 606359) signaling in Xenopus embryos and mammalian cells by binding to the extracellular domains of the Wnt coreceptors Lrp5 (603506) and Lrp6 (603507) and disrupting Wnt-induced frizzled (see 603408)-Lrp complex formation. </p><p>Using tandem affinity purification and mass spectrometry of proteins isolated from HEK293 and rat UMR-106 osteoblastic cells, Leupin et al. (2011) found that sclerostin interacted with LRP4 (604270), LRP5, and LRP6. ELISA experiments confirmed a dose-dependent interaction between recombinant LRP4 and sclerostin. Mutation analysis revealed that membrane localization mediated by the beta-propeller domain of LRP4 was required for the interaction. Overexpression of LRP4 in HEK293 cells or C28a2 human chondrocytes enhanced sclerostin-mediated inhibition of WNT1 (164820) signaling, whereas knockdown of LRP4 mRNA in HEK293 cells via RNA interference reduced sclerostin- but not DKK1 (605189)-mediated inhibition of WNT signaling. Knockdown of Lrp4 significantly blocked sclerostin inhibition of bone mineralization in mouse bone marrow stromal cells. </p>
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</span>
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<div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>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>Sclerosteosis 1</em></strong></p><p>
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In Afrikaners with sclerosteosis (SOST1; 269500), Brunkow et al. (2001) found homozygosity for a nonsense mutation in the N terminus of sclerostin (605740.0001). In an unrelated affected person of Senegalese origin reported by Tacconi et al. (1998), they found homozygosity for a splice mutation within the single intron of the SOST gene (605740.0002). </p><p>Balemans et al. (2001) described 2 families with sclerosteosis harboring homozygous mutations in the SOST gene. </p><p><strong><em>Van Buchem Disease</em></strong></p><p>
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Brunkow et al. (2001) analyzed the SOST gene in 7 Dutch patients with van Buchem disease (VBCH; 239100) and detected no mutations in the coding region. </p><p>In affected members from a large consanguineous Dutch family with van Buchem disease studied by Van Hul et al. (1998), Balemans et al. (2002) identified a homozygous 52-kb deletion approximately 35 kb downstream of the SOST gene. Three additional Dutch patients with van Buchem disease also had the deletion. The parents of affected individuals were heterozygous for the deletion. Analysis of the sequences flanking the deletion breakpoints showed the presence of Alu repeats on either side, suggesting an Alu-mediated, unequal homologous recombination event as the mechanism causing the deletion. As no coding sequences could be identified within the deleted region, Balemans et al. (2002) suggested that the deletion may alter transcription of the SOST gene in patients with van Buchem disease. </p><p>Using transgenic mice, Loots et al. (2005) characterized expression of human SOST from the wildtype allele and an allele carrying the van Buchem disease-associated 52-kb noncoding deletion downstream of SOST (VB allele). Transgenic mice with the wildtype allele expressed human SOST by embryonic day 9.5, predominantly in mesenchymal tissue of the developing limb bud, and adult transgenic mice expressed SOST in bone, kidney, and heart. These mice grew to skeletal maturity with normal body size and weight, but they displayed decreased bone mineral density. In contrast, transgenic mice expressing the VB allele did not express SOST in adult bone, and their bone parameters were indistinguishable from nontransgenic littermates. The numbers of osteocytes and osteoclasts were not significantly affected by transgenic expression, but elevated levels of SOST in transgenic mice with either allele resulted in a wide range of fused and missing digits in forelimbs and hindlimbs. Loots et al. (2005) identified 7 evolutionarily conserved regions (ECRs) within the van Buchem disease-associated deletion. They examined skeletal structures of transgenic mouse embryos expressing each of these human ECRs and found that the 250-bp ECR5 enhanced SOST expression in cartilage of ribs, vertebrae, and skull plates. ECR5 was also capable of activating the human SOST promoter in osteoblast-like cell lines. Loots et al. (2005) concluded that van Buchem disease is caused by deletion of a SOST-specific regulatory element and is allelic to sclerosteosis. </p><p><strong><em>Craniodiaphyseal Dysplasia, Autosomal Dominant</em></strong></p><p>
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In a Korean girl with autosomal dominant craniodiaphyseal dysplasia (CDD; 122860), Kim et al. (2011) identified a de novo heterozygous mutation in the SOST gene (V21M; 605740.0005). Genetic analysis of an affected patient reported by Bieganski et al. (2007) identified a second heterozygous SOST mutation affecting the same residue (V21L; 605740.0006). DNA from the possibly affected mother of the second patient was not available. Both mutations affected the secretion signal peptide of the protein, and in vitro functional expression studies showed that the mutations resulted in significantly decreased SOST secretion, although the proteins were produced in the cells. Kim et al. (2011) noted the phenotypic differences from other disorders due to SOST mutations, which are less severe and transmitted in an autosomal recessive pattern, and postulated a dominant-negative mechanism in CDD. </p><p><strong><em>SOST Polymorphisms Associated with Bone Mineral Density</em></strong></p><p>
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Uitterlinden et al. (2004) studied whether the SOST gene is an osteoporosis risk gene by examining its association with bone mineral density (BMD). They used a set of 8 polymorphisms from the SOST region to genotype 1,939 elderly men and women from a large population-based prospective cohort study of Dutch whites. They found that a 3-bp insertion in the presumed SOST promoter region, with a gene frequency of 0.38, was associated with decreased BMD in women at the femoral neck and lumbar spine, with evidence of an allele dosage effect in the oldest age group. Similarly, a G variant in the van Buchem deletion region (gene frequency = 0.40) was associated with increased BMD in men at the femoral neck and lumbar spine. In both cases, differences between extreme genotypes reached 0.2 standard deviations. No genotype effects on fracture risk were observed for the 234 osteoporotic fractures validated during 8.2 years of follow-up and for the 146 vertebral prevalent fractures analyzed. Uitterlinden et al. (2004) found evidence of additive effects of the insertion polymorphism with the Sp1-binding site polymorphism of the COL1A1 gene (120150.0051). They suggested that the moderate SOST genotype effects involved differences in regulation of SOST gene expression. </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>6 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 SCLEROSTEOSIS 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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SOST, GLN24TER
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<br />
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SNP: rs387906320,
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ClinVar: RCV000005049, RCV005089173
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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 Afrikaners with sclerosteosis (SOST1; 269500), Brunkow et al. (2001) identified a homozygous C-to-T substitution located 69 bp downstream of the predicted translation initiation site of the SOST gene, resulting in termination of translation 23 residues from the N terminus. The mutation was not found in over 400 controls. </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 SCLEROSTEOSIS 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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SOST, IVS1DS, A-T, +3 AND/OR IVS1AS, A-C, -67
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<br />
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SNP: rs114609105, rs2154590472,
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gnomAD: rs114609105,
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ClinVar: RCV000005050, RCV001843427
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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 Senegalese patient with sclerosteosis (SOST1; 269500) reported by Tacconi et al. (1998), Brunkow et al. (2001) found 2 homozygous changes in the single intron of the SOST gene. Since neither of these nucleotide differences existed in the sequence of 360 unaffected control DNAs, they concluded that one or both of them could have a deleterious effect on splicing of the mRNA. </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 SCLEROSTEOSIS 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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SOST, TRP124TER
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<br />
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SNP: rs104894644,
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ClinVar: RCV000005051
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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 Brazilian family with sclerosteosis (SOST1; 269500), Balemans et al. (2001) identified a homozygous 372G-A transition in exon 2 of the SOST gene, resulting in a trp124-to-ter nonsense mutation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 SCLEROSTEOSIS 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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SOST, ARG126TER
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<br />
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SNP: rs104894645,
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gnomAD: rs104894645,
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ClinVar: RCV000005052
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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 American family with sclerosteosis (SOST1; 269500), Balemans et al. (2001) found a homozygous 376C-T transition in exon 2 of the SOST gene, resulting in an arg126-to-ter nonsense mutation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0005 CRANIODIAPHYSEAL DYSPLASIA, AUTOSOMAL DOMINANT</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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SOST, VAL21MET
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<br />
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SNP: rs387907169,
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ClinVar: RCV000024297, RCV003398567
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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 Korean girl with autosomal dominant craniodiaphyseal dysplasia (CDD; 122860), Kim et al. (2011) identified a de novo heterozygous 61G-A transition in the SOST gene, resulting in a val21-to-met (V21M) substitution in the secretion signal of the protein. In a second patient, Kim et al. (2011) identified a different mutation affecting the same residue (V21L; 605740.0006). In vitro functional expression studies showed that the mutations resulted in significantly decreased SOST secretion, although the proteins were produced in the cells. </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>.0006 CRANIODIAPHYSEAL DYSPLASIA, AUTOSOMAL DOMINANT</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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SOST, VAL21LEU
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<br />
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SNP: rs387907169,
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ClinVar: RCV000024298
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with autosomal dominant craniodiaphyseal dysplasia (CDD; 122860), originally reported by Bieganski et al. (2007), Kim et al. (2011) identified a heterozygous 61G-T transversion in the SOST gene, resulting in a val21-to-leu (V21L) substitution in the secretion signal of the protein. DNA from his possibly affected mother was not available. An unrelated patient with the disorder had a mutation affecting the same residue (V21M; 605740.0005). In vitro functional expression studies showed that both mutations resulted in significantly decreased SOST secretion, although the proteins were produced in the cells. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
|
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Balemans, W., Ebeling, M., Patel, N., Van Hul, E., Olson, P., Dioszegi, M., Lacza, C., Wuyts, W., Van Den Ende, J., Willems, P., Paes-Alves, A. F., Hill, S., and 9 others.
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|
<strong>Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST).</strong>
|
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Hum. Molec. Genet. 10: 537-543, 2001.
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[PubMed: 11181578]
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[Full Text: https://doi.org/10.1093/hmg/10.5.537]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Balemans, W., Patel, N., Ebeling, M., Van Hul, E., Wuyts, W., Lacza, C., Dioszegi, M., Dikkers, F. G., Hildering, P., Willems, P. J., Verheij, J. B. G. M., Lindpaintner, K., Vickery, B., Foernzler, D., Van Hul, W.
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<strong>Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease.</strong>
|
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J. Med. Genet. 39: 91-97, 2002.
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[PubMed: 11836356]
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[Full Text: https://doi.org/10.1136/jmg.39.2.91]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Bieganski, T., Baranska, D., Miastkowska, I., Kobielski, A., Gorska-Chrzastek, M., Kozlowski, K.
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Uitterlinden, A. G., Arp, P. P., Paeper, B. W., Charmley, P., Proll, S., Rivadeneira, F., Fang, Y., van Meurs, J. B. J., Britschgi, T. B., Latham, J. A., Schatzman, R. C., Pols, H. A. P., Brunkow, M. E.
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<strong>Polymorphisms in the sclerosteosis/van Buchem disease gene (SOST) region are associated with bone-mineral density in elderly whites.</strong>
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