4189 lines
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Entry
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- *607035 - SUFU NEGATIVE REGULATOR OF HEDGEHOG SIGNALING; SUFU
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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">*607035</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#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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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/607035">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000107882;t=ENST00000369902" 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=51684" 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=607035" 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=ENSG00000107882;t=ENST00000369902" 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_001178133,NM_016169,XM_011539858,XM_011539860,XM_011539861,XM_011539863,XM_011539864,XM_047425335,XM_047425336,XM_047425337,XM_047425338,XM_047425339" 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_016169" 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=607035" 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=06124&isoform_id=06124_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/SUFU" 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/5739507,5802374,6689888,6689894,6808049,7025392,15342038,19923479,24710913,37182223,62511179,119570066,119570067,119570068,119570069,189065402,296011020,767963042,767963046,767963048,767963052,767963054,1231942904,1843476474,2217277514,2217277517,2217277521,2217277523,2217277525,2462519592,2462519594,2462519596,2462519598,2462519600,2462519602,2462519604,2462519606,2462519608,2462519610" 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/Q9UMX1" 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=51684" 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=ENSG00000107882;t=ENST00000369902" 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=SUFU" 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=SUFU" 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+51684" 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/SUFU" 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:51684" 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/51684" 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=chr10&hgg_gene=ENST00000369902.8&hgg_start=102502819&hgg_end=102633535&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:16466" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=607035[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=607035[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/SUFU/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000107882" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=SUFU" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=SUFU" 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=SUFU" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=SUFU&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/PA38146" 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:16466" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0005355.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1345643" 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/SUFU#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:1345643" 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/51684/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=51684" 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-030131-6223" 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">
|
|
<div style="display: table-row">
|
|
<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
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|
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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:51684" 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=SUFU&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>
|
|
<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> 1156923005, 443333004<br />
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">ICD+</a>
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</div>
|
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<div>
|
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<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Gene description">
|
|
<span class="text-danger"><strong>*</strong></span>
|
|
607035
|
|
</span>
|
|
</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>
|
|
<h3>
|
|
<span class="mim-font">
|
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SUFU NEGATIVE REGULATOR OF HEDGEHOG SIGNALING; SUFU
|
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</span>
|
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</h3>
|
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</div>
|
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<div>
|
|
<br />
|
|
</div>
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<div>
|
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<a id="alternativeTitles" class="mim-anchor"></a>
|
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<div>
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<p>
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|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
SUPPRESSOR OF FUSED, DROSOPHILA, HOMOLOG OF<br />
|
|
SUFUH
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
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<div>
|
|
<a id="includedTitles" class="mim-anchor"></a>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
Other entities represented in this entry:
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<span class="h3 mim-font">
|
|
SUFUXL, INCLUDED
|
|
</span>
|
|
</div>
|
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|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
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</div>
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<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=SUFU" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">SUFU</a></em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/10/521?start=-3&limit=10&highlight=521">10q24.32</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr10:102502819-102633535&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'})">10:102,502,819-102,633,535</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=155255,607174,620343,617757" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="4">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/10/521?start=-3&limit=10&highlight=521">
|
|
10q24.32
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
{Medulloblastoma}
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/155255"> 155255 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>, <abbr class="mim-tip-hint" title="Somatic mutation">SMu</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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|
|
</span>
|
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</td>
|
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</tr>
|
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|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
{Meningioma, familial, susceptibility to}
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/607174"> 607174 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
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<p>SUFU encodes a component of the Sonic hedgehog (SHH; <a href="/entry/600725">600725</a>)/Patched (PTCH; <a href="/entry/601309">601309</a>) signaling pathway. Mutations in genes encoding components of this pathway are deleterious for normal development and are associated with cancer-predisposing syndromes (e.g., HPE3, <a href="/entry/142945">142945</a>; BCNS, <a href="/entry/109400">109400</a>, <a href="/entry/620343">620343</a>; and GCPS, <a href="/entry/175700">175700</a>).</p>
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<p>By EST database searching for homologs of Drosophila suppressor of fused (Sufu), followed by RACE, <a href="#8" class="mim-tip-reference" title="Kogerman, P., Grimm, T., Kogerman, L., Krause, D., Unden, A. B., Sandstedt, B., Toftgard, R., Zaphiropoulos, P. G. <strong>Mammalian suppressor-of-fused modulates nuclear-cytoplasmic shuttling of Gli-1.</strong> Nature Cell Biol. 1: 312-319, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10559945/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10559945</a>] [<a href="https://doi.org/10.1038/13031" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10559945">Kogerman et al. (1999)</a> obtained a cDNA encoding human SUFU. The deduced 484-amino acid protein is 40% identical to the fly protein. Northern blot analysis detected ubiquitous expression of a minor 2.8-kb and a major 5.5-kb transcript. Whole-mount in situ hybridization analysis detected expression throughout midgestation in the neural tube and, later, in the neural tube's brain and spinal cord derivatives, overlapping with expression of Ptch and Gli1 (<a href="/entry/165220">165220</a>), Gli2 (<a href="/entry/165230">165230</a>), and Gli3 (<a href="/entry/165240">165240</a>). Similar analysis in a 12-week human embryo showed marked expression in perichondrial osteoblasts, cells that also receive a hedgehog signal. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10559945" 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="Stone, D. M., Murone, M., Luoh, S.-M., Ye, W., Armanini, M. P., Gurney, A., Phillips, H., Brush, J., Goddard, A., de Sauvage, F. J., Rosenthal, A. <strong>Characterization of the human suppressor of fused, a negative regulator of the zinc-finger transcription factor Gli.</strong> J. Cell Sci. 112: 4437-4448, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10564661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10564661</a>] [<a href="https://doi.org/10.1242/jcs.112.23.4437" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10564661">Stone et al. (1999)</a> independently cloned and characterized SUFU and identified shorter splice variants, truncated by 52 and 3 amino acids. The full-length protein, which is 97% identical to the mouse protein, contains a PEST sequence and multiple potential phosphorylation sites. In addition to the same transcripts identified by <a href="#8" class="mim-tip-reference" title="Kogerman, P., Grimm, T., Kogerman, L., Krause, D., Unden, A. B., Sandstedt, B., Toftgard, R., Zaphiropoulos, P. G. <strong>Mammalian suppressor-of-fused modulates nuclear-cytoplasmic shuttling of Gli-1.</strong> Nature Cell Biol. 1: 312-319, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10559945/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10559945</a>] [<a href="https://doi.org/10.1038/13031" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10559945">Kogerman et al. (1999)</a>, they detected smaller 2.0- and 1.0-kb transcripts in testis. By semiquantitative PCR, they determined that the full-length isoform is more abundant in all tissues. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10564661+10559945" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Grimm, T., Teglund, S., Tackels, D., Sangiorgi, E., Gurrieri, F., Schwartz, C., Toftgard, R. <strong>Genomic organization and embryonic expression of Suppressor of Fused, a candidate gene for the split-hand/split-foot malformation type 3.</strong> FEBS Lett. 505: 13-17, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11557033/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11557033</a>] [<a href="https://doi.org/10.1016/s0014-5793(01)02682-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11557033">Grimm et al. (2001)</a> identified a low abundance isoform, SUFU-XL, of 485 amino acids as well as shorter isoforms restricted to leukocytes and testis. They detected expression of normal SUFU and SUFU-XL in a panel of tumor cDNA libraries. Immunoprecipitation analysis showed that neither of the shorter isoforms is able to bind GLI1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11557033" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By genomic sequence analysis, <a href="#6" class="mim-tip-reference" title="Grimm, T., Teglund, S., Tackels, D., Sangiorgi, E., Gurrieri, F., Schwartz, C., Toftgard, R. <strong>Genomic organization and embryonic expression of Suppressor of Fused, a candidate gene for the split-hand/split-foot malformation type 3.</strong> FEBS Lett. 505: 13-17, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11557033/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11557033</a>] [<a href="https://doi.org/10.1016/s0014-5793(01)02682-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11557033">Grimm et al. (2001)</a> determined that the mouse and human SUFU genes contain 12 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11557033" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By FISH, <a href="#14" class="mim-tip-reference" title="Stone, D. M., Murone, M., Luoh, S.-M., Ye, W., Armanini, M. P., Gurney, A., Phillips, H., Brush, J., Goddard, A., de Sauvage, F. J., Rosenthal, A. <strong>Characterization of the human suppressor of fused, a negative regulator of the zinc-finger transcription factor Gli.</strong> J. Cell Sci. 112: 4437-4448, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10564661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10564661</a>] [<a href="https://doi.org/10.1242/jcs.112.23.4437" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10564661">Stone et al. (1999)</a> mapped the SUFU gene to chromosome 10q24-q25. <a href="#6" class="mim-tip-reference" title="Grimm, T., Teglund, S., Tackels, D., Sangiorgi, E., Gurrieri, F., Schwartz, C., Toftgard, R. <strong>Genomic organization and embryonic expression of Suppressor of Fused, a candidate gene for the split-hand/split-foot malformation type 3.</strong> FEBS Lett. 505: 13-17, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11557033/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11557033</a>] [<a href="https://doi.org/10.1016/s0014-5793(01)02682-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11557033">Grimm et al. (2001)</a> confirmed the localization by radiation hybrid analysis. By FISH, <a href="#16" class="mim-tip-reference" title="Taylor, M. D., Liu, L., Raffel, C., Hui, C., Mainprize, T. G., Zhang, X., Agatep, R., Chiappa, S., Gao, L., Lowrance, A., Hao, A., Goldstein, A. M., Stavrou, T., Scherer, S. W., Dura, W. T., Wainwright, B., Squire, J. A., Rutka, J. T., Hogg, D. <strong>Mutations in SUFU predispose to medulloblastoma.</strong> Nature Genet. 31: 306-310, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12068298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12068298</a>] [<a href="https://doi.org/10.1038/ng916" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12068298">Taylor et al. (2002)</a> mapped the SUFU gene to 10q24.3 distal to the PTEN gene (<a href="/entry/601728">601728</a>), which maps to 10q23.31 and is approximately 1 Mb telomeric to BTRC. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12068298+11557033+10564661" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By luciferase reporter analysis, <a href="#8" class="mim-tip-reference" title="Kogerman, P., Grimm, T., Kogerman, L., Krause, D., Unden, A. B., Sandstedt, B., Toftgard, R., Zaphiropoulos, P. G. <strong>Mammalian suppressor-of-fused modulates nuclear-cytoplasmic shuttling of Gli-1.</strong> Nature Cell Biol. 1: 312-319, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10559945/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10559945</a>] [<a href="https://doi.org/10.1038/13031" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10559945">Kogerman et al. (1999)</a> showed that SUFU inhibits the transcriptional activity of GLI1 and osteogenic differentiation in response to SHH signaling. Immunoprecipitation analysis determined that SUFU and GLI1 are associated in an intracellular complex. Confocal microscopy demonstrated both cytoplasmic and nuclear expression of SUFU; however, colocalization with GLI1, due to a central leucine-rich CRM1 (XPO1; <a href="/entry/602559">602559</a>)-dependent nuclear-export signal, was restricted to cytoplasm. Inhibition of CRM1 resulted in nuclear expression of GLI1 in the absence of full-length SUFU that has an intact C terminus necessary for GLI1-induced transcriptional activation. Truncated GLI1 bound to DNA also interacted with SUFU. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10559945" 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 GST pull-down and yeast 2-hybrid analysis, <a href="#14" class="mim-tip-reference" title="Stone, D. M., Murone, M., Luoh, S.-M., Ye, W., Armanini, M. P., Gurney, A., Phillips, H., Brush, J., Goddard, A., de Sauvage, F. J., Rosenthal, A. <strong>Characterization of the human suppressor of fused, a negative regulator of the zinc-finger transcription factor Gli.</strong> J. Cell Sci. 112: 4437-4448, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10564661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10564661</a>] [<a href="https://doi.org/10.1242/jcs.112.23.4437" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10564661">Stone et al. (1999)</a> demonstrated that SUFU interacts with GLI2 and GLI3 through its extreme C-terminal end, as well as with GLI1 and SLIMB (BTRC; <a href="/entry/603482">603482</a>). Reporter analysis indicated that BTRC containing an F-box domain potentiates the inhibitory effect of SUFU on GLI activity. <a href="#14" class="mim-tip-reference" title="Stone, D. M., Murone, M., Luoh, S.-M., Ye, W., Armanini, M. P., Gurney, A., Phillips, H., Brush, J., Goddard, A., de Sauvage, F. J., Rosenthal, A. <strong>Characterization of the human suppressor of fused, a negative regulator of the zinc-finger transcription factor Gli.</strong> J. Cell Sci. 112: 4437-4448, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10564661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10564661</a>] [<a href="https://doi.org/10.1242/jcs.112.23.4437" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10564661">Stone et al. (1999)</a> concluded that SUFU is a direct negative regulator of GLI and that this regulation may occur at multiple levels, possibly depending on the relative intracellular concentrations of different signaling components. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10564661" 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 Drosophila, Cos2 is a major inhibitor of Shh signaling, and Sufu is a minor inhibitor. <a href="#17" class="mim-tip-reference" title="Varjosalo, M., Li, S.-P., Taipale, J. <strong>Divergence of hedgehog signal transduction mechanism between Drosophila and mammals.</strong> Dev. Cell 10: 177-186, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16459297/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16459297</a>] [<a href="https://doi.org/10.1016/j.devcel.2005.12.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16459297">Varjosalo et al. (2006)</a> found the opposite was true in mouse cells; RNA interference studies indicated Sufu was a major Shh repressor and the mammalian orthologs of Cos2, Kif7 and Kif27, had no effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16459297" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Lee, D. Y., Deng, Z., Wang, C.-H., Yang, B. B. <strong>MicroRNA-378 promotes cell survival, tumor growth, and angiogenesis by targeting SuFu and Fus-1 expression.</strong> Proc. Nat. Acad. Sci. 104: 20350-20355, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18077375/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18077375</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18077375[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0706901104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18077375">Lee et al. (2007)</a> found that expression of miR378 (MIRN378; <a href="/entry/611957">611957</a>) enhanced cell survival and reduced caspase-3 (CASP3; <a href="/entry/600636">600636</a>) activity in human glioma cells. Injection of miR378-expressing glioma cells into nude mice showed that miR378 promoted tumor growth and angiogenesis. <a href="#9" class="mim-tip-reference" title="Lee, D. Y., Deng, Z., Wang, C.-H., Yang, B. B. <strong>MicroRNA-378 promotes cell survival, tumor growth, and angiogenesis by targeting SuFu and Fus-1 expression.</strong> Proc. Nat. Acad. Sci. 104: 20350-20355, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18077375/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18077375</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18077375[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0706901104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18077375">Lee et al. (2007)</a> identified miR378 target sequences in the 3-prime UTRs of SUFU and FUS1 (TUSC2; <a href="/entry/607052">607052</a>) transcripts, and they found that miR378 downregulated expression of both transcripts. Transfection and overexpression of either SUFU or FUS1 overcame the growth-promoting effects of miR378. Expression of miR378 repressed expression of reporter gene constructs harboring the miR378 target sites of SUFU or FUS1. RT-PCR and Western blot analysis showed that repression of SUFU occurred posttranscriptionally, and the levels of SUFU protein and miR378 were inversely correlated in a human cell lines. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18077375" 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>Split Hand/Foot Malformation 3</em></strong></p><p>
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<a href="#6" class="mim-tip-reference" title="Grimm, T., Teglund, S., Tackels, D., Sangiorgi, E., Gurrieri, F., Schwartz, C., Toftgard, R. <strong>Genomic organization and embryonic expression of Suppressor of Fused, a candidate gene for the split-hand/split-foot malformation type 3.</strong> FEBS Lett. 505: 13-17, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11557033/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11557033</a>] [<a href="https://doi.org/10.1016/s0014-5793(01)02682-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11557033">Grimm et al. (2001)</a> found no mutations in the SUFU gene in patients with split-hand/foot malformation type 3 (SHFM3; <a href="/entry/246560">246560</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11557033" 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="Lyle, R., Radhakrishna, U., Blouin, J.-L., Gagos, S., Everman, D. B., Gehrig, C., Delozier-Blanchet, C., Solanki, J. V., Patel, U. C., Nath, S. K., Gurrieri, F., Neri, G., Schwartz, C. E., Antonarakis, S. E. <strong>Split-hand/split-foot malformation 3 (SHFM3) at 10q24, development of rapid diagnostic methods and gene expression from the region.</strong> Am. J. Med. Genet. 140A: 1384-1395, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16691619/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16691619</a>] [<a href="https://doi.org/10.1002/ajmg.a.31247" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16691619">Lyle et al. (2006)</a> used FISH and quantitative PCR to narrow the SHFM3 locus to a minimal 325-kb duplication containing only the BTRC (<a href="/entry/603482">603482</a>) and POLL (<a href="/entry/606343">606343</a>) genes. Expression analysis of 13 candidate genes within and flanking the duplicated region showed that BTRC and SUFU, present in 3 copies and 2 copies, respectively, were overexpressed in SHFM3 patients compared to controls. <a href="#10" class="mim-tip-reference" title="Lyle, R., Radhakrishna, U., Blouin, J.-L., Gagos, S., Everman, D. B., Gehrig, C., Delozier-Blanchet, C., Solanki, J. V., Patel, U. C., Nath, S. K., Gurrieri, F., Neri, G., Schwartz, C. E., Antonarakis, S. E. <strong>Split-hand/split-foot malformation 3 (SHFM3) at 10q24, development of rapid diagnostic methods and gene expression from the region.</strong> Am. J. Med. Genet. 140A: 1384-1395, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16691619/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16691619</a>] [<a href="https://doi.org/10.1002/ajmg.a.31247" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16691619">Lyle et al. (2006)</a> suggested that SHFM3 may be caused by overexpression of BTRC and SUFU, both of which are involved in beta-catenin signaling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16691619" 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>Medulloblastoma</em></strong></p><p>
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<a href="#3" class="mim-tip-reference" title="Bayani, J., Zielenska, M., Marrano, P., Ng, Y. K., Taylor, M. D., Jay, V., Rutka, J. T., Squire, J. A. <strong>Molecular cytogenetic analysis of medulloblastomas and supratentorial primitive neuroectodermal tumors by using conventional banding, comparative genomic hybridization, and spectral karyotyping.</strong> J. Neurosurg. 93: 437-448, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10969942/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10969942</a>] [<a href="https://doi.org/10.3171/jns.2000.93.3.0437" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10969942">Bayani et al. (2000)</a> showed that loss of heterozygosity (LOH) on 10q24 is frequent in medulloblastomas (<a href="/entry/155255">155255</a>), suggesting that this region contains one or more tumor suppressor genes. <a href="#16" class="mim-tip-reference" title="Taylor, M. D., Liu, L., Raffel, C., Hui, C., Mainprize, T. G., Zhang, X., Agatep, R., Chiappa, S., Gao, L., Lowrance, A., Hao, A., Goldstein, A. M., Stavrou, T., Scherer, S. W., Dura, W. T., Wainwright, B., Squire, J. A., Rutka, J. T., Hogg, D. <strong>Mutations in SUFU predispose to medulloblastoma.</strong> Nature Genet. 31: 306-310, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12068298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12068298</a>] [<a href="https://doi.org/10.1038/ng916" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12068298">Taylor et al. (2002)</a> reported children with medulloblastoma who carried germline and somatic mutations in SUFU in the SHH pathway, accompanied by LOH of the wildtype allele (see, e.g., <a href="#0001">607035.0001</a>-<a href="#0006">607035.0006</a>). Several of these mutations encoded truncated proteins that are unable to export the GLI transcription factor (<a href="/entry/165220">165220</a>) from nucleus to cytoplasm, resulting in the activation of SHH signaling. Thus, SUFU is a tumor suppressor gene that predisposes individuals to medulloblastoma by modulating the SHH signaling pathway through a newly identified mechanism. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12068298+10969942" 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="#16" class="mim-tip-reference" title="Taylor, M. D., Liu, L., Raffel, C., Hui, C., Mainprize, T. G., Zhang, X., Agatep, R., Chiappa, S., Gao, L., Lowrance, A., Hao, A., Goldstein, A. M., Stavrou, T., Scherer, S. W., Dura, W. T., Wainwright, B., Squire, J. A., Rutka, J. T., Hogg, D. <strong>Mutations in SUFU predispose to medulloblastoma.</strong> Nature Genet. 31: 306-310, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12068298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12068298</a>] [<a href="https://doi.org/10.1038/ng916" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12068298">Taylor et al. (2002)</a> noted that all 4 medulloblastomas with SUFU truncating mutations were of the desmoplastic subtype. Desmoplastic tumors make up about 20 to 30% of medulloblastomas, have a more nodular architecture than 'classical' medulloblastoma, and may have a better prognosis. Activation of the SHH pathway is particularly high in desmoplastic medulloblastomas, as shown by increased expression of the SHH target genes GLI, SMOH (<a href="/entry/601500">601500</a>), and PTCH (<a href="/entry/601309">601309</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12068298" 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="#4" class="mim-tip-reference" title="Brugieres, L., Pierron, G., Chompret, A., Bressac-de Paillerets, B., Di Rocco, F., Varlet, P., Pierre-Kahn, A., Caron, O., Grill, J., Delattre, O. <strong>Incomplete penetrance of the predisposition to medulloblastoma associated with germ-line SUFU mutations.</strong> J. Med. Genet. 47: 142-144, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19833601/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19833601</a>] [<a href="https://doi.org/10.1136/jmg.2009.067751" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19833601">Brugieres et al. (2010)</a> identified germline truncating SUFU mutations in 2 unrelated families with several children under 3 years of age diagnosed with medulloblastoma (<a href="#0005">607035.0005</a> and <a href="#0006">607035.0006</a>, respectively). Among the 25 mutation carriers in the 2 families, 7 developed medulloblastomas; of the 5 tumors for which histology was reviewed, 3 were classified as medulloblastoma with extensive nodularity (MBEN) and 2 were typical desmoplastic/nodular medulloblastoma. No obvious physical stigmata of nevoid basal cell carcinoma syndrome was found among 21 mutation carriers from both families who were examined, including 11 patients who underwent brain MRI. SUFU sequence analysis of 1 tumor from each family confirmed that only the mutant allele was detected in the tumor DNA, thus demonstrating the loss of the wildtype allele and supporting a tumor suppressor role for SUFU. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19833601" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Susceptibility to Familial Meningioma</em></strong></p><p>
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In affected members of a Finnish family with multiple adult-onset meningiomas (<a href="/entry/607174">607174</a>), <a href="#1" class="mim-tip-reference" title="Aavikko, M., Li, S.-P., Saarinen, S., Alhopuro, P., Kaasinen, E., Morgunova, E., Li, Y., Vesanen, K., Smith, M. J., Evans, D. G. R., Poyhonen, M., Kiuru, A., Auvinen, A., Aaltonen, L. A., Taipale, J., Vahteristo, P. <strong>Loss of SUFU function in familial multiple meningioma.</strong> Am. J. Hum. Genet. 91: 520-526, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22958902/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22958902</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22958902[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2012.07.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22958902">Aavikko et al. (2012)</a> identified a germline heterozygous mutation in the SUFU gene (R123C; <a href="#0007">607035.0007</a>). The mutation was identified by genomewide linkage analysis combined with exome sequencing. Tumor tissue from 7 meningiomas showed loss of heterozygosity at the SUFU locus, consistent with a 2-hit model for tumor suppressor genes. In vitro functional expression studies in human rhabdomyosarcoma cells showed that the R123C mutant protein had a significantly decreased ability to suppress GLI1 activity compared to wildtype SUFU, resulting in aberrant activation of the hedgehog signaling pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22958902" 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>Basal Cell Nevus Syndrome 2</em></strong></p><p>
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In affected members of a family exhibiting atypical signs and symptoms of Gorlin syndrome (BCNS2; <a href="/entry/620343">620343</a>), who were known to be negative for mutation in the PTCH1 gene, <a href="#11" class="mim-tip-reference" title="Pastorino, L., Ghiorzo, P., Nasti, S., Battistuzzi, L., Cusano, R., Marzocchi, C., Garre, M. L., Clementi, M., Bianchi Scarra, G. <strong>Identification of a SUFU germline mutation in a family with Gorlin syndrome.</strong> Am. J. Med. Genet. 149A: 1539-1543, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19533801/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19533801</a>] [<a href="https://doi.org/10.1002/ajmg.a.32944" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19533801">Pastorino et al. (2009)</a> identified a splice site mutation (<a href="#0003">607035.0003</a>) that had previously been found in a desmoplastic medulloblastoma by <a href="#16" class="mim-tip-reference" title="Taylor, M. D., Liu, L., Raffel, C., Hui, C., Mainprize, T. G., Zhang, X., Agatep, R., Chiappa, S., Gao, L., Lowrance, A., Hao, A., Goldstein, A. M., Stavrou, T., Scherer, S. W., Dura, W. T., Wainwright, B., Squire, J. A., Rutka, J. T., Hogg, D. <strong>Mutations in SUFU predispose to medulloblastoma.</strong> Nature Genet. 31: 306-310, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12068298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12068298</a>] [<a href="https://doi.org/10.1038/ng916" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12068298">Taylor et al. (2002)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19533801+12068298" 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 next-generation sequencing in a 52-year-old woman and her 80-year-old mother with basel cell nevus syndrome, <a href="#2" class="mim-tip-reference" title="Alvarez-Salafranca, M., Garcia-Garcia, M., Montes-Torres, A., Rivera-Fuertes, I., Lopez-Gimenez, M. T., Ara, M. <strong>SUFU-associated Gorlin syndrome: expanding the spectrum between classic nevoid basal cell carcinoma syndrome and multiple hereditary infundibulocystic basal cell carcinoma.</strong> Australas. J. Derm. 64: 249-254, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36825822/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36825822</a>] [<a href="https://doi.org/10.1111/ajd.14014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="36825822">Alvarez-Salafranca et al. (2023)</a> identified a heterozygous 1-bp deletion in the SUFU gene (c.71del; <a href="#0005">607035.0005</a>). Both patients had infiltrative basal cell carcinomas and palmar pits. The daughter also had sagittal and parasagittal dural calcifications, thus fulfilling the 3 major criteria for Gorlin syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36825822" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 31-year-old patient with basal cell nevus syndrome, <a href="#12" class="mim-tip-reference" title="Petrosian, D., Reiter, P., Rozenberg, S. S., Petrosian, S. <strong>A case of Gorlin syndrome like phenotype with multiple infundibulocystic basal cell carcinomas in a moniliform blepharosis arrangement.</strong> JAAD Case Rep. 34: 27-31, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36941877/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36941877</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=36941877[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.jdcr.2023.01.025" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="36941877">Petrosian et al. (2023)</a> identified a c.367C-A transversion in exon 3 of the SUFU gene, resulting in an arg123-to-ser (R123S) substitution. The mutation, which was identified by sequencing of a panel of 77 genes associated with hereditary cancers, was classified as a variant of unknown significance. The patient presented with numerous facial papules and had a clinical history of basal cell carcinomas, cervical polyps, uterine fibroids, Plummer Vinson syndrome, arthritis, and decreased visual acuity due to presbyopia and vitreous detachment. Several facial papules were biopsied and were shown to be basal cell carcinomas with follicular differentiation. The patient also had graying of her hair at 13 years of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36941877" 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>Tumor Predisposition Review</em></strong></p><p>
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Through an international collaboration, <a href="#7" class="mim-tip-reference" title="Guerrini-Rousseau, L., Masliah-Planchon, J., Waszak, S. M., Alhopuro, P., Benusiglio, P. R., Bourdeaut, F., Brecht, I. B., Del Baldo, G., Dhanda, S. K., Garre, M. L., Gidding, C. E. M., Hirsch, S., and 16 others. <strong>Cancer risk and tumour spectrum in 172 patients with a germline SUFU pathogenic variation: a collaborative study of the SIOPE Host Genome Working Group.</strong> J. Med. Genet. 59: 1123-1132, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35768194/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35768194</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=35768194[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/10.1136/jmedgenet-2021-108385" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="35768194">Guerrini-Rousseau et al. (2022)</a> identified 172 carriers of SUFU pathogenic variants from 83 families, including 127 previously reported individuals. Overall, 117/172 carriers (68%) developed at least 1 tumor: medulloblastoma (86 patients; median age at diagnosis, 1.5 years), basal cell carcinoma (25 patients; median age at diagnosis, 40 years), meningioma (20 patients; median age at diagnosis, 44 years), and gonadal tumors (11 patients; median age at diagnosis, 14 years). Thirty-three carriers (28%) had multiple tumors. Sixty-four different variants were reported across the entire SUFU gene and were inherited in 73% of cases in which inheritance could be evaluated. The authors proposed screening recommendations for carriers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35768194" 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>Joubert Syndrome 32</em></strong></p><p>
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In 4 children from 2 unrelated consanguineous families with Joubert syndrome-32 (JBTS32; <a href="/entry/617757">617757</a>), <a href="#5" class="mim-tip-reference" title="De Mori, R., Romani, M., D'Arrigo, S., Zaki, M. S., Lorefice, E., Tardivo, S., Biagini, T., Stanley, V., Musaev, D., Fluss, J., Micalizzi, A., Nuovo, S., and 18 others. <strong>Hypomorphic recessive variants in SUFU impair the sonic hedgehog pathway and cause Joubert syndrome with cranio-facial and skeletal defects.</strong> Am. J. Hum. Genet. 101: 552-563, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28965847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28965847</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28965847[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2017.08.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28965847">De Mori et al. (2017)</a> identified 2 different homozygous missense mutations in the SUFU gene (I406T, <a href="#0008">607035.0008</a> and H176R, <a href="#0009">607035.0009</a>). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. In vitro functional cellular expression studies showed that both variants were hypomorphic, causing significantly reduced SUFU stability, decreased binding to GLI3, and decreased production of the repressor GLI3R. Patient cells showed altered expression levels of several SHH (<a href="/entry/600725">600725</a>) target genes, including significant overexpression of BCL2 (<a href="/entry/151430">151430</a>), GLI1 (<a href="/entry/165220">165220</a>), and PTCH1 (<a href="/entry/601309">601309</a>), indicating that the mutations impaired SUFU-mediated repression of the SHH pathway. <a href="#5" class="mim-tip-reference" title="De Mori, R., Romani, M., D'Arrigo, S., Zaki, M. S., Lorefice, E., Tardivo, S., Biagini, T., Stanley, V., Musaev, D., Fluss, J., Micalizzi, A., Nuovo, S., and 18 others. <strong>Hypomorphic recessive variants in SUFU impair the sonic hedgehog pathway and cause Joubert syndrome with cranio-facial and skeletal defects.</strong> Am. J. Hum. Genet. 101: 552-563, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28965847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28965847</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28965847[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2017.08.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28965847">De Mori et al. (2017)</a> concluded that germline mutations in the SUFU gene can cause deregulation of SHH signaling, resulting in recessive developmental defects of the central nervous system and limbs that share features of both SHH-related disorders and ciliopathies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28965847" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#15" class="mim-tip-reference" title="Svard, J., Heby-Henricson, K., Persson-Lek, M., Rozell, B., Lauth, M., Bergstrom, A., Ericson, J., Toftgard, R., Teglund, S. <strong>Genetic elimination of suppressor of fused reveals an essential repressor function in the mammalian hedgehog signaling pathway.</strong> Dev. Cell 10: 187-197, 2006. Note: Erratum: Dev. Cell 10: 409 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16459298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16459298</a>] [<a href="https://doi.org/10.1016/j.devcel.2005.12.013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16459298">Svard et al. (2006)</a> found that ablation of the mouse Sufu gene led to lethality at about embryonic day 9.5 with cephalic and neural tube defects. Fibroblasts derived from Sufu-null embryos showed high Gli-mediated Shh pathway activity that was unaffected by either Smo agonists or antagonists, but was partially sensitive to Pka (see <a href="/entry/176911">176911</a>) inhibition. Despite robust constitutive activity of Sufu-null fibroblasts, Gli1 localization remained cytoplasmic. Mice heterozygous for Sufu deletion appeared normal and were fertile; however, they developed a skin phenotype with basaloid changes and jaw keratocysts, characteristic features of BCNS. <a href="#15" class="mim-tip-reference" title="Svard, J., Heby-Henricson, K., Persson-Lek, M., Rozell, B., Lauth, M., Bergstrom, A., Ericson, J., Toftgard, R., Teglund, S. <strong>Genetic elimination of suppressor of fused reveals an essential repressor function in the mammalian hedgehog signaling pathway.</strong> Dev. Cell 10: 187-197, 2006. Note: Erratum: Dev. Cell 10: 409 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16459298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16459298</a>] [<a href="https://doi.org/10.1016/j.devcel.2005.12.013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16459298">Svard et al. (2006)</a> concluded that, in contrast to Drosophila, mammalian SUFU has a central role in SHH signaling, and its loss of function leads to potent ligand-independent activation of the SHH pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16459298" 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="#13" class="mim-tip-reference" title="Pospisilik, J. A., Schramek, D., Schnidar, H., Cronin, S. J. F., Nehme, N. T., Zhang, X., Knauf, C., Cani, P. D., Aumayr, K., Todoric, J., Bayer, M., Haschemi, A., and 14 others. <strong>Drosophila genome-wide obesity screen reveals hedgehog as a determinant of brown versus white adipose cell fate.</strong> Cell 140: 148-160, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20074523/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20074523</a>] [<a href="https://doi.org/10.1016/j.cell.2009.12.027" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20074523">Pospisilik et al. (2010)</a> found that hedgehog signaling was an important determinant of adipose cell fate in Drosophila. They targeted Sufu deletion to adipose tissue in mice and found that the mutant mice, which they called aP2-SufuKO, were born healthy and at mendelian ratios. Mutant mice displayed an immediate and obvious lean phenotype with reduced white, but not brown, adipose tissue. Adipocyte size and total numbers were reduced in mutant animals, and this was associated with elevated hedgehog signaling and dysregulation of early adipogenic factors. Lack of cutaneous and subcutaneous adipose stores in mutant mice also resulted in cold stress at normal room temperature, but not at elevated temperature. The mutant mice showed normal glucose tolerance and insulin sensitivity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20074523" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a medulloblastoma tumor (<a href="/entry/155255">155255</a>), <a href="#16" class="mim-tip-reference" title="Taylor, M. D., Liu, L., Raffel, C., Hui, C., Mainprize, T. G., Zhang, X., Agatep, R., Chiappa, S., Gao, L., Lowrance, A., Hao, A., Goldstein, A. M., Stavrou, T., Scherer, S. W., Dura, W. T., Wainwright, B., Squire, J. A., Rutka, J. T., Hogg, D. <strong>Mutations in SUFU predispose to medulloblastoma.</strong> Nature Genet. 31: 306-310, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12068298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12068298</a>] [<a href="https://doi.org/10.1038/ng916" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12068298">Taylor et al. (2002)</a> observed a nonconservative missense mutation, pro15 to leu (P15L), near the N terminus of SUFU. The mutation was accompanied by LOH in the wildtype allele. The amino acid change was caused by a 44C-T transition. The morphology of the tumor was not known. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12068298" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a patient with medulloblastoma of desmoplastic type (<a href="/entry/155255">155255</a>), <a href="#16" class="mim-tip-reference" title="Taylor, M. D., Liu, L., Raffel, C., Hui, C., Mainprize, T. G., Zhang, X., Agatep, R., Chiappa, S., Gao, L., Lowrance, A., Hao, A., Goldstein, A. M., Stavrou, T., Scherer, S. W., Dura, W. T., Wainwright, B., Squire, J. A., Rutka, J. T., Hogg, D. <strong>Mutations in SUFU predispose to medulloblastoma.</strong> Nature Genet. 31: 306-310, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12068298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12068298</a>] [<a href="https://doi.org/10.1038/ng916" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12068298">Taylor et al. (2002)</a> found a 1-bp insertion, 143insA, in exon 1 of the SUFU gene. The mutation caused frameshift followed by termination codon 69 bp 3-prime to the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12068298" 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">rs587776578 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776578;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=rs587776578" 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=rs587776578" 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=RCV000524075 OR RCV000814945 OR RCV001270787 OR RCV002291207 OR RCV002415392 OR RCV003223388" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000524075, RCV000814945, RCV001270787, RCV002291207, RCV002415392, RCV003223388" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000524075...</a>
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<p><strong><em>Medulloblastoma</em></strong></p><p>
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In a desmoplastic medulloblastoma (<a href="/entry/155255">155255</a>), <a href="#16" class="mim-tip-reference" title="Taylor, M. D., Liu, L., Raffel, C., Hui, C., Mainprize, T. G., Zhang, X., Agatep, R., Chiappa, S., Gao, L., Lowrance, A., Hao, A., Goldstein, A. M., Stavrou, T., Scherer, S. W., Dura, W. T., Wainwright, B., Squire, J. A., Rutka, J. T., Hogg, D. <strong>Mutations in SUFU predispose to medulloblastoma.</strong> Nature Genet. 31: 306-310, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12068298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12068298</a>] [<a href="https://doi.org/10.1038/ng916" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12068298">Taylor et al. (2002)</a> found an IVS8+1G-A splice donor site mutation in the SUFU gene. The mutation resulted in a frameshift at the 5-prime end and termination at the 3-prime end of exon 9. This was the second hit in this tumor, the first hit being a germline 2.5-Mb deletion (deletion encompassing SUFU; <a href="#0004">607035.0004</a>). The patient had some features suggesting basal cell nevus syndrome (<a href="/entry/620343">620343</a>). In addition to severe cognitive impairment and global developmental delay, facial features included frontal bossing, prominent jaw, and hypertelorism. Additional FISH experiments using contiguous BAC clones showed that the deletion was 2.5-2.8 Mb in size and included at least 28 genes. The most centromeric gene studied, BTRC (<a href="/entry/603482">603482</a>), was not included in the deletion. The deletion was not present in either parent. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12068298" 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>Basal Cell Nevus Syndrome 2</em></strong></p><p>
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In a father and son exhibiting atypical signs and symptoms of basal cell nevus syndrome (BCNS2; <a href="/entry/620343">620343</a>), <a href="#11" class="mim-tip-reference" title="Pastorino, L., Ghiorzo, P., Nasti, S., Battistuzzi, L., Cusano, R., Marzocchi, C., Garre, M. L., Clementi, M., Bianchi Scarra, G. <strong>Identification of a SUFU germline mutation in a family with Gorlin syndrome.</strong> Am. J. Med. Genet. 149A: 1539-1543, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19533801/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19533801</a>] [<a href="https://doi.org/10.1002/ajmg.a.32944" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19533801">Pastorino et al. (2009)</a> identified the known 1022+1G-A splice site transition in the SUFU gene. The mutation was not detected in the clinically unaffected paternal grandparents, suggesting that it arose de novo in the father; the mutation was also not found in 200 control alleles. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19533801" 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 MEDULLOBLASTOMA</strong>
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SUFU, 2.5-MB DEL
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000003754" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000003754" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000003754</a>
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<p>See <a href="#0003">607035.0003</a> and <a href="#16" class="mim-tip-reference" title="Taylor, M. D., Liu, L., Raffel, C., Hui, C., Mainprize, T. G., Zhang, X., Agatep, R., Chiappa, S., Gao, L., Lowrance, A., Hao, A., Goldstein, A. M., Stavrou, T., Scherer, S. W., Dura, W. T., Wainwright, B., Squire, J. A., Rutka, J. T., Hogg, D. <strong>Mutations in SUFU predispose to medulloblastoma.</strong> Nature Genet. 31: 306-310, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12068298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12068298</a>] [<a href="https://doi.org/10.1038/ng916" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12068298">Taylor et al. (2002)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12068298" 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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BASAL CELL NEVUS SYNDROME 2, INCLUDED
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SUFU, 1-BP DEL, 71C
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587776579 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776579;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=rs587776579" 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=rs587776579" 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=RCV001385138 OR RCV001573665 OR RCV002291208 OR RCV003227597 OR RCV003298027" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001385138, RCV001573665, RCV002291208, RCV003227597, RCV003298027" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001385138...</a>
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<p><strong><em>Medulloblastoma</em></strong></p><p>
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In 2 brothers who were diagnosed with medulloblastoma with extensive nodularity (MBEN; see <a href="/entry/155255">155255</a>) within the first 3 months of life, <a href="#4" class="mim-tip-reference" title="Brugieres, L., Pierron, G., Chompret, A., Bressac-de Paillerets, B., Di Rocco, F., Varlet, P., Pierre-Kahn, A., Caron, O., Grill, J., Delattre, O. <strong>Incomplete penetrance of the predisposition to medulloblastoma associated with germ-line SUFU mutations.</strong> J. Med. Genet. 47: 142-144, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19833601/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19833601</a>] [<a href="https://doi.org/10.1136/jmg.2009.067751" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19833601">Brugieres et al. (2010)</a> identified heterozygosity for a 1-bp deletion (71delC) in exon 1 of the SUFU gene, resulting in a frameshift and premature stop codon. The deletion was also identified in the unaffected mother, as well as the maternal grandfather, who had leiomyosarcoma, and 2 other unaffected relatives. The deletion was not found in 70 controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19833601" 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>Basal Cell Nevus Syndrome 2</em></strong></p><p>
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In a 52-year-old patient and her 80-year-old mother with basal cell nevus syndrome-2 (BCNS2; <a href="/entry/620343">620343</a>), <a href="#2" class="mim-tip-reference" title="Alvarez-Salafranca, M., Garcia-Garcia, M., Montes-Torres, A., Rivera-Fuertes, I., Lopez-Gimenez, M. T., Ara, M. <strong>SUFU-associated Gorlin syndrome: expanding the spectrum between classic nevoid basal cell carcinoma syndrome and multiple hereditary infundibulocystic basal cell carcinoma.</strong> Australas. J. Derm. 64: 249-254, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36825822/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36825822</a>] [<a href="https://doi.org/10.1111/ajd.14014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="36825822">Alvarez-Salafranca et al. (2023)</a> identified heterozygosity for the c.71del mutation in the SUFU gene, predicted to result in a frameshift and premature termination (Pro24ArgfsTer72). The mutation was identified by sequencing of genes associated with Gorlin syndrome. Both patients had infiltrative basal cell carcinomas and palmar pits. The daughter also had sagittal and parasagittal dural calcifications. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36825822" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 MEDULLOBLASTOMA</strong>
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SUFU, 1-BP INS, 71C
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587776579 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776579;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=rs587776579" 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=rs587776579" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV001041597 OR RCV001523824 OR RCV002371757" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001041597, RCV001523824, RCV002371757" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001041597...</a>
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<p>In 3 female cousins diagnosed with medulloblastoma (<a href="/entry/155255">155255</a>) before 3 years of age, 2 of whom had the desmoplastic type and 1 with medulloblastoma with extensive nodularity (MBEN), <a href="#4" class="mim-tip-reference" title="Brugieres, L., Pierron, G., Chompret, A., Bressac-de Paillerets, B., Di Rocco, F., Varlet, P., Pierre-Kahn, A., Caron, O., Grill, J., Delattre, O. <strong>Incomplete penetrance of the predisposition to medulloblastoma associated with germ-line SUFU mutations.</strong> J. Med. Genet. 47: 142-144, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19833601/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19833601</a>] [<a href="https://doi.org/10.1136/jmg.2009.067751" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19833601">Brugieres et al. (2010)</a> identified heterozygosity for a 1-bp insertion (71insC) in exon 1 of the SUFU gene, resulting in a frameshift and premature stop codon. The maternal aunt of 1 of the cousins also died of medulloblastoma in childhood, and the sister of another of the cousins died suddenly at 18 months of age with postmortem radiologic findings that were consistent with medulloblastoma. The insertion was present in 17 of 33 family members, 1 of whom had breast cancer and another meningioma, but not found in 70 controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19833601" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0007 MENINGIOMA, FAMILIAL, SUSCEPTIBILITY TO</strong>
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SUFU, ARG123CYS (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs202247756;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs202247756</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">rs202247756 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs202247756;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=rs202247756" 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=rs202247756" 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=RCV000030790 OR RCV002453276 OR RCV004797768" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000030790, RCV002453276, RCV004797768" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000030790...</a>
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<p>In affected members of a Finnish family with multiple adult-onset meningiomas (<a href="/entry/607174">607174</a>), <a href="#1" class="mim-tip-reference" title="Aavikko, M., Li, S.-P., Saarinen, S., Alhopuro, P., Kaasinen, E., Morgunova, E., Li, Y., Vesanen, K., Smith, M. J., Evans, D. G. R., Poyhonen, M., Kiuru, A., Auvinen, A., Aaltonen, L. A., Taipale, J., Vahteristo, P. <strong>Loss of SUFU function in familial multiple meningioma.</strong> Am. J. Hum. Genet. 91: 520-526, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22958902/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22958902</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22958902[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2012.07.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22958902">Aavikko et al. (2012)</a> identified a germline heterozygous 367C-T transition in the SUFU gene, resulting in an arg123-to-cys (R123C) substitution (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs202247756;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs202247756</a>) in the core of the N-terminal subdomain, which is central for the loop structure of the protein. The mutation, which was identified by genomewide linkage analysis combined with exome sequencing, was not found in 180 controls. Tumor tissue from 7 meningiomas showed loss of heterozygosity at the SUFU locus. In vitro functional expression studies in human rhabdomyosarcoma cells showed that the R123C mutant protein had a significantly decreased ability to suppress GLI1 (<a href="/entry/165220">165220</a>) activity compared to wildtype SUFU, resulting in aberrant activation of the hedgehog signaling pathway. Compared to the wildtype protein, the mutant protein was expressed at lower levels and also bound to GLI1 less well. Mutant SUFU was also unable to relocalize GLI1 into the cytoplasm. These studies all indicated that the R123C mutation results in a partial loss of SUFU function. Mutations in the SUFU gene were not found in 162 additional Finnish patients with meningiomas. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22958902" 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>.0008 JOUBERT SYNDROME 32</strong>
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SUFU, ILE406THR
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1554854758 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1554854758;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=rs1554854758" 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=rs1554854758" 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=RCV000515186 OR RCV001211553" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000515186, RCV001211553" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000515186...</a>
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<p>In 2 sibs, born of consanguineous Italian parents (family COR369) with Joubert syndrome-32 (JBTS32; <a href="/entry/617757">617757</a>), <a href="#5" class="mim-tip-reference" title="De Mori, R., Romani, M., D'Arrigo, S., Zaki, M. S., Lorefice, E., Tardivo, S., Biagini, T., Stanley, V., Musaev, D., Fluss, J., Micalizzi, A., Nuovo, S., and 18 others. <strong>Hypomorphic recessive variants in SUFU impair the sonic hedgehog pathway and cause Joubert syndrome with cranio-facial and skeletal defects.</strong> Am. J. Hum. Genet. 101: 552-563, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28965847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28965847</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28965847[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2017.08.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28965847">De Mori et al. (2017)</a> identified a homozygous c.1217T-C transition (c.1217T-C, NM_016169.3) in the SUFU gene, resulting in an ile406-to-thr (I406T) substitution. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not found in the dbSNP, Exome Variant Server, or gnomAD database, or in an in-house database of over 6,000 samples. In vitro functional cellular expression assays showed that the mutant protein had decreased stability compared to wildtype and had abnormal subcellular localization, tending to form intracytoplasmic aggregates. The mutant protein also had reduced binding affinity to GLI3 (<a href="/entry/165240">165240</a>), resulting in impaired repression of the SHH (<a href="/entry/600725">600725</a>) pathway in basal conditions, which was demonstrated in patient fibroblasts. The patients also carried a homozygous T716S mutation in the CDHR1 gene (<a href="/entry/609502">609502</a>), mutations in which cause later-onset cone-rod dystrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28965847" 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">rs1554852272 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1554852272;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=rs1554852272" 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=rs1554852272" 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=RCV000515250" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000515250" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000515250</a>
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<p>In 2 sibs, born of consanguineous Egyptian parents (family MTI-2023), with Joubert syndrome-32 (JBTS32; <a href="/entry/617757">617757</a>), <a href="#5" class="mim-tip-reference" title="De Mori, R., Romani, M., D'Arrigo, S., Zaki, M. S., Lorefice, E., Tardivo, S., Biagini, T., Stanley, V., Musaev, D., Fluss, J., Micalizzi, A., Nuovo, S., and 18 others. <strong>Hypomorphic recessive variants in SUFU impair the sonic hedgehog pathway and cause Joubert syndrome with cranio-facial and skeletal defects.</strong> Am. J. Hum. Genet. 101: 552-563, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28965847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28965847</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28965847[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2017.08.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28965847">De Mori et al. (2017)</a> identified a homozygous c.527A-G transition (c.527A-G, NM_016169.3) in the SUFU gene, resulting in a his176-to-arg (H176R) substitution. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not found in the dbSNP, Exome Variant Server, or gnomAD database, or in an in-house database of over 6,000 samples. In vitro functional cellular expression assays showed that the mutant protein had decreased stability compared to wildtype, but subcellular localization was similar to wildtype. The mutant protein also had reduced binding affinity to GLI3 (<a href="/entry/165240">165240</a>), resulting in impaired repression of the SHH (<a href="/entry/600725">600725</a>) pathway in basal conditions, which was demonstrated in patient fibroblasts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28965847" 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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<a id="Aavikko2012" class="mim-anchor"></a>
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Aavikko, M., Li, S.-P., Saarinen, S., Alhopuro, P., Kaasinen, E., Morgunova, E., Li, Y., Vesanen, K., Smith, M. J., Evans, D. G. R., Poyhonen, M., Kiuru, A., Auvinen, A., Aaltonen, L. A., Taipale, J., Vahteristo, P.
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<strong>Loss of SUFU function in familial multiple meningioma.</strong>
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Am. J. Hum. Genet. 91: 520-526, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22958902/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22958902</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22958902[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=22958902" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ajhg.2012.07.015" target="_blank">Full Text</a>]
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Alvarez-Salafranca, M., Garcia-Garcia, M., Montes-Torres, A., Rivera-Fuertes, I., Lopez-Gimenez, M. T., Ara, M.
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<strong>SUFU-associated Gorlin syndrome: expanding the spectrum between classic nevoid basal cell carcinoma syndrome and multiple hereditary infundibulocystic basal cell carcinoma.</strong>
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Australas. J. Derm. 64: 249-254, 2023.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36825822/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36825822</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36825822" 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/ajd.14014" target="_blank">Full Text</a>]
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Bayani, J., Zielenska, M., Marrano, P., Ng, Y. K., Taylor, M. D., Jay, V., Rutka, J. T., Squire, J. A.
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<strong>Molecular cytogenetic analysis of medulloblastomas and supratentorial primitive neuroectodermal tumors by using conventional banding, comparative genomic hybridization, and spectral karyotyping.</strong>
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J. Neurosurg. 93: 437-448, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10969942/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10969942</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10969942" 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/10.3171/jns.2000.93.3.0437" target="_blank">Full Text</a>]
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Brugieres, L., Pierron, G., Chompret, A., Bressac-de Paillerets, B., Di Rocco, F., Varlet, P., Pierre-Kahn, A., Caron, O., Grill, J., Delattre, O.
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<strong>Incomplete penetrance of the predisposition to medulloblastoma associated with germ-line SUFU mutations.</strong>
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J. Med. Genet. 47: 142-144, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19833601/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19833601</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19833601" 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.2009.067751" target="_blank">Full Text</a>]
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De Mori, R., Romani, M., D'Arrigo, S., Zaki, M. S., Lorefice, E., Tardivo, S., Biagini, T., Stanley, V., Musaev, D., Fluss, J., Micalizzi, A., Nuovo, S., and 18 others.
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<strong>Hypomorphic recessive variants in SUFU impair the sonic hedgehog pathway and cause Joubert syndrome with cranio-facial and skeletal defects.</strong>
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Am. J. Hum. Genet. 101: 552-563, 2017.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28965847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28965847</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28965847[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=28965847" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ajhg.2017.08.017" target="_blank">Full Text</a>]
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Grimm, T., Teglund, S., Tackels, D., Sangiorgi, E., Gurrieri, F., Schwartz, C., Toftgard, R.
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<strong>Genomic organization and embryonic expression of Suppressor of Fused, a candidate gene for the split-hand/split-foot malformation type 3.</strong>
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FEBS Lett. 505: 13-17, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11557033/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11557033</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11557033" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0014-5793(01)02682-5" target="_blank">Full Text</a>]
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Guerrini-Rousseau, L., Masliah-Planchon, J., Waszak, S. M., Alhopuro, P., Benusiglio, P. R., Bourdeaut, F., Brecht, I. B., Del Baldo, G., Dhanda, S. K., Garre, M. L., Gidding, C. E. M., Hirsch, S., and 16 others.
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<strong>Cancer risk and tumour spectrum in 172 patients with a germline SUFU pathogenic variation: a collaborative study of the SIOPE Host Genome Working Group.</strong>
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[<a href="https://doi.org/10.1136/jmedgenet-2021-108385" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/13031" target="_blank">Full Text</a>]
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<strong>MicroRNA-378 promotes cell survival, tumor growth, and angiogenesis by targeting SuFu and Fus-1 expression.</strong>
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[<a href="https://doi.org/10.1073/pnas.0706901104" target="_blank">Full Text</a>]
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Lyle, R., Radhakrishna, U., Blouin, J.-L., Gagos, S., Everman, D. B., Gehrig, C., Delozier-Blanchet, C., Solanki, J. V., Patel, U. C., Nath, S. K., Gurrieri, F., Neri, G., Schwartz, C. E., Antonarakis, S. E.
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<strong>Split-hand/split-foot malformation 3 (SHFM3) at 10q24, development of rapid diagnostic methods and gene expression from the region.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16691619/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16691619</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16691619" 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.31247" target="_blank">Full Text</a>]
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Pastorino, L., Ghiorzo, P., Nasti, S., Battistuzzi, L., Cusano, R., Marzocchi, C., Garre, M. L., Clementi, M., Bianchi Scarra, G.
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<strong>Identification of a SUFU germline mutation in a family with Gorlin syndrome.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19533801/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19533801</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19533801" 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.32944" target="_blank">Full Text</a>]
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Petrosian, D., Reiter, P., Rozenberg, S. S., Petrosian, S.
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<strong>A case of Gorlin syndrome like phenotype with multiple infundibulocystic basal cell carcinomas in a moniliform blepharosis arrangement.</strong>
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JAAD Case Rep. 34: 27-31, 2023.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36941877/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36941877</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=36941877[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=36941877" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.jdcr.2023.01.025" target="_blank">Full Text</a>]
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Pospisilik, J. A., Schramek, D., Schnidar, H., Cronin, S. J. F., Nehme, N. T., Zhang, X., Knauf, C., Cani, P. D., Aumayr, K., Todoric, J., Bayer, M., Haschemi, A., and 14 others.
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<strong>Drosophila genome-wide obesity screen reveals hedgehog as a determinant of brown versus white adipose cell fate.</strong>
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Cell 140: 148-160, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20074523/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20074523</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20074523" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.cell.2009.12.027" target="_blank">Full Text</a>]
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Stone, D. M., Murone, M., Luoh, S.-M., Ye, W., Armanini, M. P., Gurney, A., Phillips, H., Brush, J., Goddard, A., de Sauvage, F. J., Rosenthal, A.
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<strong>Characterization of the human suppressor of fused, a negative regulator of the zinc-finger transcription factor Gli.</strong>
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J. Cell Sci. 112: 4437-4448, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10564661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10564661</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10564661" 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/10.1242/jcs.112.23.4437" target="_blank">Full Text</a>]
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Svard, J., Heby-Henricson, K., Persson-Lek, M., Rozell, B., Lauth, M., Bergstrom, A., Ericson, J., Toftgard, R., Teglund, S.
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<strong>Genetic elimination of suppressor of fused reveals an essential repressor function in the mammalian hedgehog signaling pathway.</strong>
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Dev. Cell 10: 187-197, 2006. Note: Erratum: Dev. Cell 10: 409 only, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16459298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16459298</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16459298" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.devcel.2005.12.013" target="_blank">Full Text</a>]
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Taylor, M. D., Liu, L., Raffel, C., Hui, C., Mainprize, T. G., Zhang, X., Agatep, R., Chiappa, S., Gao, L., Lowrance, A., Hao, A., Goldstein, A. M., Stavrou, T., Scherer, S. W., Dura, W. T., Wainwright, B., Squire, J. A., Rutka, J. T., Hogg, D.
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<strong>Mutations in SUFU predispose to medulloblastoma.</strong>
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Nature Genet. 31: 306-310, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12068298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12068298</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12068298" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng916" target="_blank">Full Text</a>]
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Varjosalo, M., Li, S.-P., Taipale, J.
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<strong>Divergence of hedgehog signal transduction mechanism between Drosophila and mammals.</strong>
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Dev. Cell 10: 177-186, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16459297/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16459297</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16459297" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.devcel.2005.12.014" target="_blank">Full Text</a>]
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Hilary J. Vernon - updated : 05/17/2023
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Carol A. Bocchini - updated : 04/25/2023<br>Cassandra L. Kniffin - updated : 11/06/2017<br>Cassandra L. Kniffin - updated : 9/24/2012<br>Marla J. F. O'Neill - updated : 8/25/2010<br>Patricia A. Hartz - updated : 1/27/2010<br>Marla J. F. O'Neill - updated : 12/4/2009<br>Patricia A. Hartz - updated : 4/16/2008<br>Marla J. F. O'Neill - updated : 4/13/2007<br>Patricia A. Hartz - updated : 3/28/2006<br>Victor A. McKusick - updated : 6/18/2002
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carol : 05/18/2023
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carol : 05/17/2023<br>carol : 04/25/2023<br>carol : 04/21/2023<br>alopez : 10/12/2022<br>carol : 08/23/2019<br>alopez : 11/07/2017<br>ckniffin : 11/06/2017<br>terry : 12/19/2012<br>terry : 12/19/2012<br>terry : 9/26/2012<br>carol : 9/26/2012<br>ckniffin : 9/24/2012<br>wwang : 6/13/2011<br>wwang : 8/30/2010<br>wwang : 8/30/2010<br>terry : 8/25/2010<br>mgross : 1/28/2010<br>terry : 1/27/2010<br>carol : 12/23/2009<br>terry : 12/4/2009<br>terry : 10/8/2008<br>mgross : 9/30/2008<br>mgross : 4/16/2008<br>wwang : 5/2/2007<br>wwang : 4/20/2007<br>terry : 4/13/2007<br>wwang : 4/24/2006<br>wwang : 4/3/2006<br>terry : 3/28/2006<br>tkritzer : 11/19/2002<br>alopez : 7/26/2002<br>joanna : 6/24/2002<br>alopez : 6/20/2002<br>terry : 6/18/2002<br>carol : 6/13/2002<br>carol : 6/13/2002<br>carol : 6/13/2002
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<strong>*</strong> 607035
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SUFU NEGATIVE REGULATOR OF HEDGEHOG SIGNALING; SUFU
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SUPPRESSOR OF FUSED, DROSOPHILA, HOMOLOG OF<br />
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SUFUH
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</h4>
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<span class="mim-font">
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Other entities represented in this entry:
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</span>
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</p>
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</div>
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<div>
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<span class="h3 mim-font">
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SUFUXL, INCLUDED
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</span>
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</div>
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</div>
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<div>
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<br />
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: SUFU</em></strong>
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 1156923005, 443333004;
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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: 10q24.32
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Genomic coordinates <span class="small">(GRCh38)</span> : 10:102,502,819-102,633,535 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="4">
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<span class="mim-font">
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10q24.32
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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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{Medulloblastoma}
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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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155255
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant; Autosomal recessive; Somatic mutation
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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{Meningioma, familial, susceptibility to}
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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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607174
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal 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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3
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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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Basal cell nevus syndrome 2
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</span>
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</td>
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<td>
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<span class="mim-font">
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620343
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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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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Joubert syndrome 32
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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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617757
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>SUFU encodes a component of the Sonic hedgehog (SHH; 600725)/Patched (PTCH; 601309) signaling pathway. Mutations in genes encoding components of this pathway are deleterious for normal development and are associated with cancer-predisposing syndromes (e.g., HPE3, 142945; BCNS, 109400, 620343; and GCPS, 175700).</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By EST database searching for homologs of Drosophila suppressor of fused (Sufu), followed by RACE, Kogerman et al. (1999) obtained a cDNA encoding human SUFU. The deduced 484-amino acid protein is 40% identical to the fly protein. Northern blot analysis detected ubiquitous expression of a minor 2.8-kb and a major 5.5-kb transcript. Whole-mount in situ hybridization analysis detected expression throughout midgestation in the neural tube and, later, in the neural tube's brain and spinal cord derivatives, overlapping with expression of Ptch and Gli1 (165220), Gli2 (165230), and Gli3 (165240). Similar analysis in a 12-week human embryo showed marked expression in perichondrial osteoblasts, cells that also receive a hedgehog signal. </p><p>Stone et al. (1999) independently cloned and characterized SUFU and identified shorter splice variants, truncated by 52 and 3 amino acids. The full-length protein, which is 97% identical to the mouse protein, contains a PEST sequence and multiple potential phosphorylation sites. In addition to the same transcripts identified by Kogerman et al. (1999), they detected smaller 2.0- and 1.0-kb transcripts in testis. By semiquantitative PCR, they determined that the full-length isoform is more abundant in all tissues. </p><p>Grimm et al. (2001) identified a low abundance isoform, SUFU-XL, of 485 amino acids as well as shorter isoforms restricted to leukocytes and testis. They detected expression of normal SUFU and SUFU-XL in a panel of tumor cDNA libraries. Immunoprecipitation analysis showed that neither of the shorter isoforms is able to bind GLI1. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By genomic sequence analysis, Grimm et al. (2001) determined that the mouse and human SUFU genes contain 12 exons. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By FISH, Stone et al. (1999) mapped the SUFU gene to chromosome 10q24-q25. Grimm et al. (2001) confirmed the localization by radiation hybrid analysis. By FISH, Taylor et al. (2002) mapped the SUFU gene to 10q24.3 distal to the PTEN gene (601728), which maps to 10q23.31 and is approximately 1 Mb telomeric to BTRC. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By luciferase reporter analysis, Kogerman et al. (1999) showed that SUFU inhibits the transcriptional activity of GLI1 and osteogenic differentiation in response to SHH signaling. Immunoprecipitation analysis determined that SUFU and GLI1 are associated in an intracellular complex. Confocal microscopy demonstrated both cytoplasmic and nuclear expression of SUFU; however, colocalization with GLI1, due to a central leucine-rich CRM1 (XPO1; 602559)-dependent nuclear-export signal, was restricted to cytoplasm. Inhibition of CRM1 resulted in nuclear expression of GLI1 in the absence of full-length SUFU that has an intact C terminus necessary for GLI1-induced transcriptional activation. Truncated GLI1 bound to DNA also interacted with SUFU. </p><p>By GST pull-down and yeast 2-hybrid analysis, Stone et al. (1999) demonstrated that SUFU interacts with GLI2 and GLI3 through its extreme C-terminal end, as well as with GLI1 and SLIMB (BTRC; 603482). Reporter analysis indicated that BTRC containing an F-box domain potentiates the inhibitory effect of SUFU on GLI activity. Stone et al. (1999) concluded that SUFU is a direct negative regulator of GLI and that this regulation may occur at multiple levels, possibly depending on the relative intracellular concentrations of different signaling components. </p><p>In Drosophila, Cos2 is a major inhibitor of Shh signaling, and Sufu is a minor inhibitor. Varjosalo et al. (2006) found the opposite was true in mouse cells; RNA interference studies indicated Sufu was a major Shh repressor and the mammalian orthologs of Cos2, Kif7 and Kif27, had no effect. </p><p>Lee et al. (2007) found that expression of miR378 (MIRN378; 611957) enhanced cell survival and reduced caspase-3 (CASP3; 600636) activity in human glioma cells. Injection of miR378-expressing glioma cells into nude mice showed that miR378 promoted tumor growth and angiogenesis. Lee et al. (2007) identified miR378 target sequences in the 3-prime UTRs of SUFU and FUS1 (TUSC2; 607052) transcripts, and they found that miR378 downregulated expression of both transcripts. Transfection and overexpression of either SUFU or FUS1 overcame the growth-promoting effects of miR378. Expression of miR378 repressed expression of reporter gene constructs harboring the miR378 target sites of SUFU or FUS1. RT-PCR and Western blot analysis showed that repression of SUFU occurred posttranscriptionally, and the levels of SUFU protein and miR378 were inversely correlated in a human cell lines. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Split Hand/Foot Malformation 3</em></strong></p><p>
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Grimm et al. (2001) found no mutations in the SUFU gene in patients with split-hand/foot malformation type 3 (SHFM3; 246560). </p><p>Lyle et al. (2006) used FISH and quantitative PCR to narrow the SHFM3 locus to a minimal 325-kb duplication containing only the BTRC (603482) and POLL (606343) genes. Expression analysis of 13 candidate genes within and flanking the duplicated region showed that BTRC and SUFU, present in 3 copies and 2 copies, respectively, were overexpressed in SHFM3 patients compared to controls. Lyle et al. (2006) suggested that SHFM3 may be caused by overexpression of BTRC and SUFU, both of which are involved in beta-catenin signaling. </p><p><strong><em>Medulloblastoma</em></strong></p><p>
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Bayani et al. (2000) showed that loss of heterozygosity (LOH) on 10q24 is frequent in medulloblastomas (155255), suggesting that this region contains one or more tumor suppressor genes. Taylor et al. (2002) reported children with medulloblastoma who carried germline and somatic mutations in SUFU in the SHH pathway, accompanied by LOH of the wildtype allele (see, e.g., 607035.0001-607035.0006). Several of these mutations encoded truncated proteins that are unable to export the GLI transcription factor (165220) from nucleus to cytoplasm, resulting in the activation of SHH signaling. Thus, SUFU is a tumor suppressor gene that predisposes individuals to medulloblastoma by modulating the SHH signaling pathway through a newly identified mechanism. </p><p>Taylor et al. (2002) noted that all 4 medulloblastomas with SUFU truncating mutations were of the desmoplastic subtype. Desmoplastic tumors make up about 20 to 30% of medulloblastomas, have a more nodular architecture than 'classical' medulloblastoma, and may have a better prognosis. Activation of the SHH pathway is particularly high in desmoplastic medulloblastomas, as shown by increased expression of the SHH target genes GLI, SMOH (601500), and PTCH (601309). </p><p>Brugieres et al. (2010) identified germline truncating SUFU mutations in 2 unrelated families with several children under 3 years of age diagnosed with medulloblastoma (607035.0005 and 607035.0006, respectively). Among the 25 mutation carriers in the 2 families, 7 developed medulloblastomas; of the 5 tumors for which histology was reviewed, 3 were classified as medulloblastoma with extensive nodularity (MBEN) and 2 were typical desmoplastic/nodular medulloblastoma. No obvious physical stigmata of nevoid basal cell carcinoma syndrome was found among 21 mutation carriers from both families who were examined, including 11 patients who underwent brain MRI. SUFU sequence analysis of 1 tumor from each family confirmed that only the mutant allele was detected in the tumor DNA, thus demonstrating the loss of the wildtype allele and supporting a tumor suppressor role for SUFU. </p><p><strong><em>Susceptibility to Familial Meningioma</em></strong></p><p>
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In affected members of a Finnish family with multiple adult-onset meningiomas (607174), Aavikko et al. (2012) identified a germline heterozygous mutation in the SUFU gene (R123C; 607035.0007). The mutation was identified by genomewide linkage analysis combined with exome sequencing. Tumor tissue from 7 meningiomas showed loss of heterozygosity at the SUFU locus, consistent with a 2-hit model for tumor suppressor genes. In vitro functional expression studies in human rhabdomyosarcoma cells showed that the R123C mutant protein had a significantly decreased ability to suppress GLI1 activity compared to wildtype SUFU, resulting in aberrant activation of the hedgehog signaling pathway. </p><p><strong><em>Basal Cell Nevus Syndrome 2</em></strong></p><p>
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In affected members of a family exhibiting atypical signs and symptoms of Gorlin syndrome (BCNS2; 620343), who were known to be negative for mutation in the PTCH1 gene, Pastorino et al. (2009) identified a splice site mutation (607035.0003) that had previously been found in a desmoplastic medulloblastoma by Taylor et al. (2002). </p><p>By next-generation sequencing in a 52-year-old woman and her 80-year-old mother with basel cell nevus syndrome, Alvarez-Salafranca et al. (2023) identified a heterozygous 1-bp deletion in the SUFU gene (c.71del; 607035.0005). Both patients had infiltrative basal cell carcinomas and palmar pits. The daughter also had sagittal and parasagittal dural calcifications, thus fulfilling the 3 major criteria for Gorlin syndrome. </p><p>In a 31-year-old patient with basal cell nevus syndrome, Petrosian et al. (2023) identified a c.367C-A transversion in exon 3 of the SUFU gene, resulting in an arg123-to-ser (R123S) substitution. The mutation, which was identified by sequencing of a panel of 77 genes associated with hereditary cancers, was classified as a variant of unknown significance. The patient presented with numerous facial papules and had a clinical history of basal cell carcinomas, cervical polyps, uterine fibroids, Plummer Vinson syndrome, arthritis, and decreased visual acuity due to presbyopia and vitreous detachment. Several facial papules were biopsied and were shown to be basal cell carcinomas with follicular differentiation. The patient also had graying of her hair at 13 years of age. </p><p><strong><em>Tumor Predisposition Review</em></strong></p><p>
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Through an international collaboration, Guerrini-Rousseau et al. (2022) identified 172 carriers of SUFU pathogenic variants from 83 families, including 127 previously reported individuals. Overall, 117/172 carriers (68%) developed at least 1 tumor: medulloblastoma (86 patients; median age at diagnosis, 1.5 years), basal cell carcinoma (25 patients; median age at diagnosis, 40 years), meningioma (20 patients; median age at diagnosis, 44 years), and gonadal tumors (11 patients; median age at diagnosis, 14 years). Thirty-three carriers (28%) had multiple tumors. Sixty-four different variants were reported across the entire SUFU gene and were inherited in 73% of cases in which inheritance could be evaluated. The authors proposed screening recommendations for carriers. </p><p><strong><em>Joubert Syndrome 32</em></strong></p><p>
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In 4 children from 2 unrelated consanguineous families with Joubert syndrome-32 (JBTS32; 617757), De Mori et al. (2017) identified 2 different homozygous missense mutations in the SUFU gene (I406T, 607035.0008 and H176R, 607035.0009). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. In vitro functional cellular expression studies showed that both variants were hypomorphic, causing significantly reduced SUFU stability, decreased binding to GLI3, and decreased production of the repressor GLI3R. Patient cells showed altered expression levels of several SHH (600725) target genes, including significant overexpression of BCL2 (151430), GLI1 (165220), and PTCH1 (601309), indicating that the mutations impaired SUFU-mediated repression of the SHH pathway. De Mori et al. (2017) concluded that germline mutations in the SUFU gene can cause deregulation of SHH signaling, resulting in recessive developmental defects of the central nervous system and limbs that share features of both SHH-related disorders and ciliopathies. </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>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Svard et al. (2006) found that ablation of the mouse Sufu gene led to lethality at about embryonic day 9.5 with cephalic and neural tube defects. Fibroblasts derived from Sufu-null embryos showed high Gli-mediated Shh pathway activity that was unaffected by either Smo agonists or antagonists, but was partially sensitive to Pka (see 176911) inhibition. Despite robust constitutive activity of Sufu-null fibroblasts, Gli1 localization remained cytoplasmic. Mice heterozygous for Sufu deletion appeared normal and were fertile; however, they developed a skin phenotype with basaloid changes and jaw keratocysts, characteristic features of BCNS. Svard et al. (2006) concluded that, in contrast to Drosophila, mammalian SUFU has a central role in SHH signaling, and its loss of function leads to potent ligand-independent activation of the SHH pathway. </p><p>Pospisilik et al. (2010) found that hedgehog signaling was an important determinant of adipose cell fate in Drosophila. They targeted Sufu deletion to adipose tissue in mice and found that the mutant mice, which they called aP2-SufuKO, were born healthy and at mendelian ratios. Mutant mice displayed an immediate and obvious lean phenotype with reduced white, but not brown, adipose tissue. Adipocyte size and total numbers were reduced in mutant animals, and this was associated with elevated hedgehog signaling and dysregulation of early adipogenic factors. Lack of cutaneous and subcutaneous adipose stores in mutant mice also resulted in cold stress at normal room temperature, but not at elevated temperature. The mutant mice showed normal glucose tolerance and insulin sensitivity. </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>9 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 MEDULLOBLASTOMA, SOMATIC</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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SUFU, PRO15LEU
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<br />
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SNP: rs28942088,
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ClinVar: RCV000003750, RCV004772827
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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 medulloblastoma tumor (155255), Taylor et al. (2002) observed a nonconservative missense mutation, pro15 to leu (P15L), near the N terminus of SUFU. The mutation was accompanied by LOH in the wildtype allele. The amino acid change was caused by a 44C-T transition. The morphology of the tumor was not known. </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 MEDULLOBLASTOMA</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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SUFU, 1-BP INS, 143A
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<br />
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SNP: rs1589970134,
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ClinVar: RCV002291206
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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 medulloblastoma of desmoplastic type (155255), Taylor et al. (2002) found a 1-bp insertion, 143insA, in exon 1 of the SUFU gene. The mutation caused frameshift followed by termination codon 69 bp 3-prime to the 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>.0003 MEDULLOBLASTOMA, SOMATIC</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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BASAL CELL NEVUS SYNDROME 2, INCLUDED
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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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SUFU, IVS8, G-A, +1
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<br />
|
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SNP: rs587776578,
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ClinVar: RCV000524075, RCV000814945, RCV001270787, RCV002291207, RCV002415392, RCV003223388
|
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|
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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 />
|
|
<p><strong><em>Medulloblastoma</em></strong></p><p>
|
|
In a desmoplastic medulloblastoma (155255), Taylor et al. (2002) found an IVS8+1G-A splice donor site mutation in the SUFU gene. The mutation resulted in a frameshift at the 5-prime end and termination at the 3-prime end of exon 9. This was the second hit in this tumor, the first hit being a germline 2.5-Mb deletion (deletion encompassing SUFU; 607035.0004). The patient had some features suggesting basal cell nevus syndrome (620343). In addition to severe cognitive impairment and global developmental delay, facial features included frontal bossing, prominent jaw, and hypertelorism. Additional FISH experiments using contiguous BAC clones showed that the deletion was 2.5-2.8 Mb in size and included at least 28 genes. The most centromeric gene studied, BTRC (603482), was not included in the deletion. The deletion was not present in either parent. </p><p><strong><em>Basal Cell Nevus Syndrome 2</em></strong></p><p>
|
|
In a father and son exhibiting atypical signs and symptoms of basal cell nevus syndrome (BCNS2; 620343), Pastorino et al. (2009) identified the known 1022+1G-A splice site transition in the SUFU gene. The mutation was not detected in the clinically unaffected paternal grandparents, suggesting that it arose de novo in the father; the mutation was also not found in 200 control alleles. </p>
|
|
</span>
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</div>
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<div>
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<br />
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|
</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 MEDULLOBLASTOMA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
SUFU, 2.5-MB DEL
|
|
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|
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<br />
|
|
|
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ClinVar: RCV000003754
|
|
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|
|
|
</span>
|
|
</div>
|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>See 607035.0003 and Taylor et al. (2002). </p>
|
|
</span>
|
|
</div>
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<div>
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<br />
|
|
</div>
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</div>
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<div>
|
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 MEDULLOBLASTOMA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
BASAL CELL NEVUS SYNDROME 2, INCLUDED
|
|
</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
SUFU, 1-BP DEL, 71C
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|
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|
<br />
|
|
|
|
SNP: rs587776579,
|
|
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|
|
|
ClinVar: RCV001385138, RCV001573665, RCV002291208, RCV003227597, RCV003298027
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p />
|
|
<p><strong><em>Medulloblastoma</em></strong></p><p>
|
|
In 2 brothers who were diagnosed with medulloblastoma with extensive nodularity (MBEN; see 155255) within the first 3 months of life, Brugieres et al. (2010) identified heterozygosity for a 1-bp deletion (71delC) in exon 1 of the SUFU gene, resulting in a frameshift and premature stop codon. The deletion was also identified in the unaffected mother, as well as the maternal grandfather, who had leiomyosarcoma, and 2 other unaffected relatives. The deletion was not found in 70 controls. </p><p><strong><em>Basal Cell Nevus Syndrome 2</em></strong></p><p>
|
|
In a 52-year-old patient and her 80-year-old mother with basal cell nevus syndrome-2 (BCNS2; 620343), Alvarez-Salafranca et al. (2023) identified heterozygosity for the c.71del mutation in the SUFU gene, predicted to result in a frameshift and premature termination (Pro24ArgfsTer72). The mutation was identified by sequencing of genes associated with Gorlin syndrome. Both patients had infiltrative basal cell carcinomas and palmar pits. The daughter also had sagittal and parasagittal dural calcifications. </p>
|
|
</span>
|
|
</div>
|
|
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|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 MEDULLOBLASTOMA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SUFU, 1-BP INS, 71C
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587776579,
|
|
|
|
|
|
|
|
ClinVar: RCV001041597, RCV001523824, RCV002371757
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 female cousins diagnosed with medulloblastoma (155255) before 3 years of age, 2 of whom had the desmoplastic type and 1 with medulloblastoma with extensive nodularity (MBEN), Brugieres et al. (2010) identified heterozygosity for a 1-bp insertion (71insC) in exon 1 of the SUFU gene, resulting in a frameshift and premature stop codon. The maternal aunt of 1 of the cousins also died of medulloblastoma in childhood, and the sister of another of the cousins died suddenly at 18 months of age with postmortem radiologic findings that were consistent with medulloblastoma. The insertion was present in 17 of 33 family members, 1 of whom had breast cancer and another meningioma, but not found in 70 controls. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 MENINGIOMA, FAMILIAL, SUSCEPTIBILITY TO</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SUFU, ARG123CYS ({dbSNP rs202247756})
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs202247756,
|
|
|
|
|
|
|
|
ClinVar: RCV000030790, RCV002453276, RCV004797768
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a Finnish family with multiple adult-onset meningiomas (607174), Aavikko et al. (2012) identified a germline heterozygous 367C-T transition in the SUFU gene, resulting in an arg123-to-cys (R123C) substitution (rs202247756) in the core of the N-terminal subdomain, which is central for the loop structure of the protein. The mutation, which was identified by genomewide linkage analysis combined with exome sequencing, was not found in 180 controls. Tumor tissue from 7 meningiomas showed loss of heterozygosity at the SUFU locus. In vitro functional expression studies in human rhabdomyosarcoma cells showed that the R123C mutant protein had a significantly decreased ability to suppress GLI1 (165220) activity compared to wildtype SUFU, resulting in aberrant activation of the hedgehog signaling pathway. Compared to the wildtype protein, the mutant protein was expressed at lower levels and also bound to GLI1 less well. Mutant SUFU was also unable to relocalize GLI1 into the cytoplasm. These studies all indicated that the R123C mutation results in a partial loss of SUFU function. Mutations in the SUFU gene were not found in 162 additional Finnish patients with meningiomas. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 JOUBERT SYNDROME 32</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SUFU, ILE406THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1554854758,
|
|
|
|
|
|
|
|
ClinVar: RCV000515186, RCV001211553
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sibs, born of consanguineous Italian parents (family COR369) with Joubert syndrome-32 (JBTS32; 617757), De Mori et al. (2017) identified a homozygous c.1217T-C transition (c.1217T-C, NM_016169.3) in the SUFU gene, resulting in an ile406-to-thr (I406T) substitution. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not found in the dbSNP, Exome Variant Server, or gnomAD database, or in an in-house database of over 6,000 samples. In vitro functional cellular expression assays showed that the mutant protein had decreased stability compared to wildtype and had abnormal subcellular localization, tending to form intracytoplasmic aggregates. The mutant protein also had reduced binding affinity to GLI3 (165240), resulting in impaired repression of the SHH (600725) pathway in basal conditions, which was demonstrated in patient fibroblasts. The patients also carried a homozygous T716S mutation in the CDHR1 gene (609502), mutations in which cause later-onset cone-rod dystrophy. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 JOUBERT SYNDROME 32</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SUFU, HIS176ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1554852272,
|
|
|
|
|
|
|
|
ClinVar: RCV000515250
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sibs, born of consanguineous Egyptian parents (family MTI-2023), with Joubert syndrome-32 (JBTS32; 617757), De Mori et al. (2017) identified a homozygous c.527A-G transition (c.527A-G, NM_016169.3) in the SUFU gene, resulting in a his176-to-arg (H176R) substitution. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not found in the dbSNP, Exome Variant Server, or gnomAD database, or in an in-house database of over 6,000 samples. In vitro functional cellular expression assays showed that the mutant protein had decreased stability compared to wildtype, but subcellular localization was similar to wildtype. The mutant protein also had reduced binding affinity to GLI3 (165240), resulting in impaired repression of the SHH (600725) pathway in basal conditions, which was demonstrated in patient fibroblasts. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
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|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Aavikko, M., Li, S.-P., Saarinen, S., Alhopuro, P., Kaasinen, E., Morgunova, E., Li, Y., Vesanen, K., Smith, M. J., Evans, D. G. R., Poyhonen, M., Kiuru, A., Auvinen, A., Aaltonen, L. A., Taipale, J., Vahteristo, P.
|
|
<strong>Loss of SUFU function in familial multiple meningioma.</strong>
|
|
Am. J. Hum. Genet. 91: 520-526, 2012.
|
|
|
|
|
|
[PubMed: 22958902]
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|
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|
[Full Text: https://doi.org/10.1016/j.ajhg.2012.07.015]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Alvarez-Salafranca, M., Garcia-Garcia, M., Montes-Torres, A., Rivera-Fuertes, I., Lopez-Gimenez, M. T., Ara, M.
|
|
<strong>SUFU-associated Gorlin syndrome: expanding the spectrum between classic nevoid basal cell carcinoma syndrome and multiple hereditary infundibulocystic basal cell carcinoma.</strong>
|
|
Australas. J. Derm. 64: 249-254, 2023.
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|
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|
|
[PubMed: 36825822]
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[Full Text: https://doi.org/10.1111/ajd.14014]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Bayani, J., Zielenska, M., Marrano, P., Ng, Y. K., Taylor, M. D., Jay, V., Rutka, J. T., Squire, J. A.
|
|
<strong>Molecular cytogenetic analysis of medulloblastomas and supratentorial primitive neuroectodermal tumors by using conventional banding, comparative genomic hybridization, and spectral karyotyping.</strong>
|
|
J. Neurosurg. 93: 437-448, 2000.
|
|
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|
|
[PubMed: 10969942]
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[Full Text: https://doi.org/10.3171/jns.2000.93.3.0437]
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Brugieres, L., Pierron, G., Chompret, A., Bressac-de Paillerets, B., Di Rocco, F., Varlet, P., Pierre-Kahn, A., Caron, O., Grill, J., Delattre, O.
|
|
<strong>Incomplete penetrance of the predisposition to medulloblastoma associated with germ-line SUFU mutations.</strong>
|
|
J. Med. Genet. 47: 142-144, 2010.
|
|
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|
|
[PubMed: 19833601]
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|
[Full Text: https://doi.org/10.1136/jmg.2009.067751]
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|
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</p>
|
|
</li>
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|
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<li>
|
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<p class="mim-text-font">
|
|
De Mori, R., Romani, M., D'Arrigo, S., Zaki, M. S., Lorefice, E., Tardivo, S., Biagini, T., Stanley, V., Musaev, D., Fluss, J., Micalizzi, A., Nuovo, S., and 18 others.
|
|
<strong>Hypomorphic recessive variants in SUFU impair the sonic hedgehog pathway and cause Joubert syndrome with cranio-facial and skeletal defects.</strong>
|
|
Am. J. Hum. Genet. 101: 552-563, 2017.
|
|
|
|
|
|
[PubMed: 28965847]
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|
|
[Full Text: https://doi.org/10.1016/j.ajhg.2017.08.017]
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Grimm, T., Teglund, S., Tackels, D., Sangiorgi, E., Gurrieri, F., Schwartz, C., Toftgard, R.
|
|
<strong>Genomic organization and embryonic expression of Suppressor of Fused, a candidate gene for the split-hand/split-foot malformation type 3.</strong>
|
|
FEBS Lett. 505: 13-17, 2001.
|
|
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|
|
|
[PubMed: 11557033]
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|
|
[Full Text: https://doi.org/10.1016/s0014-5793(01)02682-5]
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Guerrini-Rousseau, L., Masliah-Planchon, J., Waszak, S. M., Alhopuro, P., Benusiglio, P. R., Bourdeaut, F., Brecht, I. B., Del Baldo, G., Dhanda, S. K., Garre, M. L., Gidding, C. E. M., Hirsch, S., and 16 others.
|
|
<strong>Cancer risk and tumour spectrum in 172 patients with a germline SUFU pathogenic variation: a collaborative study of the SIOPE Host Genome Working Group.</strong>
|
|
J. Med. Genet. 59: 1123-1132, 2022.
|
|
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|
|
|
[PubMed: 35768194]
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|
|
[Full Text: https://doi.org/10.1136/jmedgenet-2021-108385]
|
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</p>
|
|
</li>
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|
<li>
|
|
<p class="mim-text-font">
|
|
Kogerman, P., Grimm, T., Kogerman, L., Krause, D., Unden, A. B., Sandstedt, B., Toftgard, R., Zaphiropoulos, P. G.
|
|
<strong>Mammalian suppressor-of-fused modulates nuclear-cytoplasmic shuttling of Gli-1.</strong>
|
|
Nature Cell Biol. 1: 312-319, 1999.
|
|
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|
|
[PubMed: 10559945]
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|
|
[Full Text: https://doi.org/10.1038/13031]
|
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</p>
|
|
</li>
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<li>
|
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<p class="mim-text-font">
|
|
Lee, D. Y., Deng, Z., Wang, C.-H., Yang, B. B.
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Lyle, R., Radhakrishna, U., Blouin, J.-L., Gagos, S., Everman, D. B., Gehrig, C., Delozier-Blanchet, C., Solanki, J. V., Patel, U. C., Nath, S. K., Gurrieri, F., Neri, G., Schwartz, C. E., Antonarakis, S. E.
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Petrosian, D., Reiter, P., Rozenberg, S. S., Petrosian, S.
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<strong>A case of Gorlin syndrome like phenotype with multiple infundibulocystic basal cell carcinomas in a moniliform blepharosis arrangement.</strong>
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Pospisilik, J. A., Schramek, D., Schnidar, H., Cronin, S. J. F., Nehme, N. T., Zhang, X., Knauf, C., Cani, P. D., Aumayr, K., Todoric, J., Bayer, M., Haschemi, A., and 14 others.
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<strong>Drosophila genome-wide obesity screen reveals hedgehog as a determinant of brown versus white adipose cell fate.</strong>
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Stone, D. M., Murone, M., Luoh, S.-M., Ye, W., Armanini, M. P., Gurney, A., Phillips, H., Brush, J., Goddard, A., de Sauvage, F. J., Rosenthal, A.
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Taylor, M. D., Liu, L., Raffel, C., Hui, C., Mainprize, T. G., Zhang, X., Agatep, R., Chiappa, S., Gao, L., Lowrance, A., Hao, A., Goldstein, A. M., Stavrou, T., Scherer, S. W., Dura, W. T., Wainwright, B., Squire, J. A., Rutka, J. T., Hogg, D.
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