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Entry
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- *613899 - FANCC GENE; FANCC
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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">*613899</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<a href="#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/613899">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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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=ENSG00000158169;t=ENST00000289081" 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=2176" 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=613899" 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=ENSG00000158169;t=ENST00000289081" 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_000136,NM_001243743,NM_001243744,XM_005251802,XM_006717001,XM_006717002,XM_006717004,XM_011518365,XM_011518366,XM_024447451,XM_047422948,XM_047422949,XM_047422950,XM_047422951,XM_047422952,XM_047422953,XM_047422954,XM_047422955,XM_047422956,XM_047422957,XM_047422958,XM_047422959" 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_000136" 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=613899" 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://www.proteinatlas.org/search/FANCC" 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/31295,31297,182336,1706762,16041738,28144175,56118236,119613032,119613033,119613034,119613035,194389272,344217746,344217748,530390729,578817176,578817178,578817182,767956618,767956621,957949350,957949353,1370514024,2217376032,2217376034,2217376037,2217376039,2217376041,2217376043,2217376045,2217376049,2217376051,2217376053,2217376055,2217376057,2462623334,2462623336,2462623338,2462623340,2462623342,2462623344,2462623346,2462623348,2462623350,2462623352,2462623354,2462623356,2462623358,2462623360,2462623362,2462623364,2462623366,2462623368" 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/Q00597" 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=2176" 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=ENSG00000158169;t=ENST00000289081" 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=FANCC" 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=FANCC" 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+2176" 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/FANCC" 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:2176" 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/2176" 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=chr9&hgg_gene=ENST00000289081.8&hgg_start=95099054&hgg_end=95317709&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:3584" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:3584" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/fancc" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=613899[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=613899[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/FANCC/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/ENSG00000158169" 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=FANCC" 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=FANCC" 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=FANCC" 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=FANCC&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/PA27997" 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:3584" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:95480" 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/FANCC#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:95480" 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/2176/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=2176" 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-060510-2" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:2176" 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=FANCC&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 1285021005<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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613899
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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FANCC GENE; FANCC
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
FAC; FACC
|
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=FANCC" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">FANCC</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
|
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Cytogenetic location: <a href="/geneMap/9/330?start=-3&limit=10&highlight=330">9q22.32</a>
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr9:95099054-95317709&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'})">9:95,099,054-95,317,709</a> </span>
|
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</em>
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</strong>
|
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
|
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<br />
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</div>
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<div>
|
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
|
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<tr class="active">
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<th>
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Location
|
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</th>
|
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
|
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</th>
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</tr>
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</thead>
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<tbody>
|
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|
<tr>
|
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<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/9/330?start=-3&limit=10&highlight=330">
|
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9q22.32
|
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</a>
|
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</span>
|
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</td>
|
|
|
|
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<td>
|
|
<span class="mim-font">
|
|
Fanconi anemia, complementation group C
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<a href="/entry/227645"> 227645 </a>
|
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|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
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|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/613899" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/613899" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
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<br />
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</div>
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<div>
|
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<a id="text" class="mim-anchor"></a>
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<p>The FANCC gene is one of a group of classical Fanconi anemia genes whose protein products physically interact in a multiprotein core complex. The main function of this core complex with E3 ubiquitin ligase activity appears to be the posttranslational activations of FANCD2 (<a href="/entry/613984">613984</a>) and FANCI (<a href="/entry/611360">611360</a>) by monoubiquitination of specific lysine residues (summary by <a href="#9" class="mim-tip-reference" title="Hartmann, L., Neveling, K., Borkens, S., Schneider, H., Freund, M., Grassman, E., Theiss, S., Wawer, A., Burdach, S., Auerbach, A. D., Schindler, D., Hanenberg, H., Schaal, H. <strong>Correct mRNA processing at a mutant TT splice donor in FANCC ameliorates the clinical phenotype in patients and is enhanced by delivery of suppressor U1 snRNAs.</strong> Am. J. Hum. Genet. 87: 480-493, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20869034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20869034</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20869034[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.2010.08.016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20869034">Hartmann et al., 2010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20869034" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using a functional complementation method, <a href="#30" class="mim-tip-reference" title="Strathdee, C. A., Gavish, H., Shannon, W. R., Buchwald, M. <strong>Cloning of cDNAs for Fanconi's anaemia by functional complementation.</strong> Nature 356: 763-767, 1992. Note: Erratum: Nature 358: 434 only, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1574115/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1574115</a>] [<a href="https://doi.org/10.1038/356763a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1574115">Strathdee et al. (1992)</a> cloned cDNAs that corrected the defect of Fanconi anemia group C cells. The cDNAs encoded alternatively processed transcripts of a new gene, designated FACC, mutated in patients with Fanconi anemia complementation group C. FACC transcripts were detected in a wide variety of tissues and cell lines by use of PCR with reverse-transcribed RNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1574115" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Gavish, H., dos Santos, C. C., Buchwald, M. <strong>A leu554-to-pro substitution completely abolishes the functional complementing activity of the Fanconi anemia (FACC) protein.</strong> Hum. Molec. Genet. 2: 123-126, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8499901/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8499901</a>] [<a href="https://doi.org/10.1093/hmg/2.2.123" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8499901">Gavish et al. (1993)</a> corrected the previously published FACC cDNA sequence which omitted 3 nucleotides. The corrected sequence predicts a 1,677-bp ORF and a protein of 558 amino acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8499901" 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="#34" class="mim-tip-reference" title="Wevrick, R., Barker, J. E., Eppig, J. T., Nadeau, J. H., Buchwald, M. <strong>Expression of the Fanconi anemia group C gene in the mouse. (Abstract)</strong> Am. J. Hum. Genet. 51 (suppl.): A137 only, 1992."None>Wevrick et al. (1992)</a> cloned cDNAs corresponding to the mouse Facc gene. The sequence of the human and mouse proteins are 81% identical. The mouse gene encodes a protein of 558 amino acids, compared to 557 amino acids in the human protein.</p>
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<p><a href="#6" class="mim-tip-reference" title="Gibson, R. A., Buchwald, M., Roberts, R. G., Mathew, C. G. <strong>Characterisation of the exon structure of the Fanconi anaemia group C gene by vectorette PCR.</strong> Hum. Molec. Genet. 2: 35-38, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8490620/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8490620</a>] [<a href="https://doi.org/10.1093/hmg/2.1.35" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8490620">Gibson et al. (1993)</a> isolated a YAC clone containing the FACC gene and used vectorette PCR to determine that the gene contains 14 exons. (Vectorette PCR was illustrated by their Figure 1. It was performed according to the method of <a href="#25" class="mim-tip-reference" title="Riley, J., Butler, R., Ogilvie, D., Finniear, R., Jenner, D., Powell, S., Anand, R., Smith, J. C., Markham, A. F. <strong>A novel, rapid method for the isolation of terminal sequences from yeast artificial chromosome (YAC) clones.</strong> Nucleic Acids Res. 18: 2887-2890, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2161516/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2161516</a>] [<a href="https://doi.org/10.1093/nar/18.10.2887" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2161516">Riley et al. (1990)</a>, described in detail by <a href="#26" class="mim-tip-reference" title="Roberts, R. G., Coffey, A. J., Bobrow, M., Bentley, D. R. <strong>Determination of the exon structure of the distal portion of the dystrophin gene by vectorette PCR.</strong> Genomics 13: 942-950, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1505985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1505985</a>] [<a href="https://doi.org/10.1016/0888-7543(92)90005-d" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1505985">Roberts et al. (1992)</a>.) <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2161516+8490620+1505985" 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>Several different forms of FACC mRNA that share the same coding region have been isolated. At least 2 species result from the use of alternative exons at the 5-prime end, and 3 result from the use of distinct polyadenylation signals. <a href="#27" class="mim-tip-reference" title="Savoia, A., Centra, M., Ianzano, L., de Cillis, G. P., Zelante, L., Buchwald, M. <strong>Characterization of the 5-prime region of the Fanconi anaemia group C (FACC) gene.</strong> Hum. Molec. Genet. 4: 1321-1326, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7581369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7581369</a>] [<a href="https://doi.org/10.1093/hmg/4.8.1321" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7581369">Savoia et al. (1995)</a> isolated genomic clones corresponding to the 5-prime region, including a putative promoter and 2 alternate 5-prime exons. These exons, which they referred to as exons -1 and -1a, were found to be separated by a small intron, with exon -1 located 5-prime to the exon -1a. Further, these exons were flanked by consensus sequences of donor sites at the 5-prime ends of introns. An acceptor splice site was not evident 5-prime of exon -1a, suggesting that exon -1 is not spliced onto exon -1a. The sequences upstream of exon -1 and -1a had no obvious TATA or CAAT boxes but included CG-rich sequences. <a href="#27" class="mim-tip-reference" title="Savoia, A., Centra, M., Ianzano, L., de Cillis, G. P., Zelante, L., Buchwald, M. <strong>Characterization of the 5-prime region of the Fanconi anaemia group C (FACC) gene.</strong> Hum. Molec. Genet. 4: 1321-1326, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7581369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7581369</a>] [<a href="https://doi.org/10.1093/hmg/4.8.1321" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7581369">Savoia et al. (1995)</a> suggested that mutations affecting the 5-prime UTR and the promoter region may underlie some cases of Fanconi anemia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7581369" 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="#29" class="mim-tip-reference" title="Strathdee, C. A., Duncan, A. M. V., Buchwald, M. <strong>Evidence for at least four Fanconi anaemia genes including FACC on chromosome 9.</strong> Nature Genet. 1: 196-198, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1303234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1303234</a>] [<a href="https://doi.org/10.1038/ng0692-196" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1303234">Strathdee et al. (1992)</a> mapped the FACC gene to chromosome 9q22.3 by in situ hybridization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1303234" 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="#7" class="mim-tip-reference" title="Gibson, R. A., Ford, D., Jansen, S., Savoia, A., Havenga, C., Milner, R. D., de Ravel, T. J., Cohn, R. J., Ball, S. E., Roberts, I., Llerena, J. C., Vorechovsky, I., Pearson, T., Birjandi, F., Hussein, S. S., Murer-Orlando, M., Easton, D. F., Mathew, C. G. <strong>Genetic mapping of the FACC gene and linkage analysis in Fanconi anaemia families.</strong> J. Med. Genet. 31: 868-871, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7853372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7853372</a>] [<a href="https://doi.org/10.1136/jmg.31.11.868" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7853372">Gibson et al. (1994)</a> used a polymorphism within the FACC gene to localize it within a 5-cM interval on 9q, bounded by D9S196/D9S197 and D9S176. Linkage analysis with 3 highly informative microsatellite polymorphisms flanking the FACC locus in 36 Fanconi anemia families showed that only 8% of them were linked to 9q22.3. The markers also allowed rapid exclusion of 56% of the families in the panel from complementation group C, thus substantially reducing the number of patients who need to be screened for FACC mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7853372" 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 interspecific backcross analysis, <a href="#35" class="mim-tip-reference" title="Wevrick, R., Barker, J. E., Nadeau, J. H., Szpirer, C., Buchwald, M. <strong>Mapping of the murine and rat Facc genes and assessment of flexed-tail as a candidate mouse homolog of Fanconi anemia group C.</strong> Mammalian Genome 4: 440-444, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7690622/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7690622</a>] [<a href="https://doi.org/10.1007/BF00296818" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7690622">Wevrick et al. (1993)</a> showed that the cloned mouse homolog of Facc is located on mouse chromosome 13; the rat homolog is located on chromosome 17. A previously described anemic mouse mutant, 'flexed-tail,' had been mapped to the same region of chromosome 13. However, the authors found no evidence that Facc is mutated in flexed-tail mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7690622" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using a polyclonal antiserum against FACC and by immunofluorescence and subcellular fractionation studies of human cell lines, <a href="#42" class="mim-tip-reference" title="Youssoufian, H. <strong>Localization of Fanconi anemia C protein to the cytoplasm of mammalian cells.</strong> Proc. Nat. Acad. Sci. 91: 7975-7979, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8058745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8058745</a>] [<a href="https://doi.org/10.1073/pnas.91.17.7975" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8058745">Youssoufian (1994)</a> showed that the FACC protein was localized primarily to the cytoplasm under steady-state conditions, transient through the cell cycle, and exposure to crosslinking or cytotoxic agents. These observations suggested an indirect role for FACC in regulating DNA repair in group C Fanconi anemia. <a href="#39" class="mim-tip-reference" title="Yamashita, T., Barber, D. L., Zhu, Y., Wu, N., D'Andrea, A. D. <strong>The Fanconi anemia polypeptide FACC is localized to the cytoplasm.</strong> Proc. Nat. Acad. Sci. 91: 6712-6716, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7517562/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7517562</a>] [<a href="https://doi.org/10.1073/pnas.91.14.6712" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7517562">Yamashita et al. (1994)</a> found that the wildtype FACC was a 60-kD protein, consistent with its predicted molecular mass. Different Fanconi anemia group C cell lines expressed full-length FACC, truncated FACC, or no detectable FACC polypeptide. In addition, the antiserum specifically immunoprecipitated a 50-kD and a 150-kD FACC-related protein (FRP-50 and FRP-150, respectively). Cell fractionation and immunofluorescence studies demonstrated that the FACC polypeptide localizes to the cytoplasm. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8058745+7517562" 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>The pathogenesis of the bone marrow failure that is a consistent feature of Fanconi anemia was investigated by <a href="#28" class="mim-tip-reference" title="Segal, G. M., Magenis, R. E., Brown, M., Keeble, W., Smith, T. D., Heinrich, M. C., Bagby, G. C., Jr. <strong>Repression of Fanconi anemia gene (FACC) expression inhibits growth of hematopoietic progenitor cells.</strong> J. Clin. Invest. 94: 846-852, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7518843/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7518843</a>] [<a href="https://doi.org/10.1172/JCI117405" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7518843">Segal et al. (1994)</a>, who pointed out that it is not known whether the pancytopenia is a direct and specific result of the inherited mutation or a consequence of accumulated stem cell losses resulting from the nonspecific DNA damage that is characteristic of the disease. They tested the hypothesis that the FACC protein plays a regulatory role in hematopoiesis by exposing normal human lymphocytes, bone marrow cells, endothelial cells, and fibroblasts to an antisense oligodeoxynucleotide (ODN) complementary to bases -4 to +14 of FACC mRNA. The mitomycin C assay demonstrated that the antisense ODN, but not missense or sense ODNs, repressed FACC gene expression in lymphocytes. The antisense ODN substantially reduced cytoplasmic levels of FACC mRNA in bone marrow cells and lymphocytes. Escalating doses of antisense ODN increasingly inhibited clonal growth of erythroid and granulocyte-macrophage progenitor cells but did not inhibit growth of fibroblasts or endothelial cells. <a href="#28" class="mim-tip-reference" title="Segal, G. M., Magenis, R. E., Brown, M., Keeble, W., Smith, T. D., Heinrich, M. C., Bagby, G. C., Jr. <strong>Repression of Fanconi anemia gene (FACC) expression inhibits growth of hematopoietic progenitor cells.</strong> J. Clin. Invest. 94: 846-852, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7518843/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7518843</a>] [<a href="https://doi.org/10.1172/JCI117405" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7518843">Segal et al. (1994)</a> concluded that while the FACC gene product plays a role in defining cellular tolerance to crosslinking agents, it also functions to regulate growth, differentiation, and/or survival of normal hematopoietic progenitor cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7518843" 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>Although abnormalities in DNA repair had been suspected in Fanconi anemia complementation group C, localization of the FAC gene product to the cytoplasm had cast doubt on such a mechanism. <a href="#43" class="mim-tip-reference" title="Youssoufian, H. <strong>Cytoplasmic localization of FAC is essential for the correction of a prerepair defect in Fanconi anemia group C cells.</strong> J. Clin. Invest. 97: 2003-2010, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8621788/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8621788</a>] [<a href="https://doi.org/10.1172/JCI118635" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8621788">Youssoufian (1996)</a> monitored interstrand DNA crosslinking and found that the predominant defect in group C cells is in the initial induction of crosslinks, not in repair synthesis. The author demonstrated that both the crosslinking defect and the enhanced cytotoxicity of crosslinkers on Fanconi anemia group C cells were corrected completely by cytoplasmic isoforms of the FAC protein, but not by an isoform targeted to the nucleus. Furthermore, the major molecular defect in these cells preceded crosslink repair. <a href="#43" class="mim-tip-reference" title="Youssoufian, H. <strong>Cytoplasmic localization of FAC is essential for the correction of a prerepair defect in Fanconi anemia group C cells.</strong> J. Clin. Invest. 97: 2003-2010, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8621788/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8621788</a>] [<a href="https://doi.org/10.1172/JCI118635" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8621788">Youssoufian (1996)</a> also showed that the ability of FAC to impart resistance to FA-C cells reached a threshold despite overexpression of the gene product. <a href="#43" class="mim-tip-reference" title="Youssoufian, H. <strong>Cytoplasmic localization of FAC is essential for the correction of a prerepair defect in Fanconi anemia group C cells.</strong> J. Clin. Invest. 97: 2003-2010, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8621788/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8621788</a>] [<a href="https://doi.org/10.1172/JCI118635" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8621788">Youssoufian (1996)</a> proposed a cellular defense pathway for genotoxic agents in which FAC acts through a cytoplasmic compartment and at a proximal step within this pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8621788" 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>The tumor suppressor protein p53 (<a href="/entry/191170">191170</a>) can bind to specific target sequences and activate transcription of genes adjacent to these DNA elements. <a href="#13" class="mim-tip-reference" title="Liebetrau, W., Budde, A., Savoia, A., Grummt, F., Hoehn, H. <strong>p53 activates Fanconi anemia group C gene expression.</strong> Hum. Molec. Genet. 6: 277-283, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9063748/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9063748</a>] [<a href="https://doi.org/10.1093/hmg/6.2.277" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9063748">Liebetrau et al. (1997)</a> noted that there are 2 p53 binding sites in the FACC gene, 1 in the promoter region and 1 in the coding region. Gel shift experiments showed that wildtype p53 protein binds to the p53 target sequence in the promoter region of the FACC gene. Transfection experiments showed that overexpression of wildtype p53 in human diploid fibroblasts and lymphoblasts augmented transcription of the FACC gene up to 3-fold. The transfection efficiency was approximately 15% for both cell types. The FACC expression activity for transformed cells was stimulated to an estimated level of 18- to 21-fold upon p53 overexpression. The tumor-derived p53 mutants, his175 and his273, that failed to bind DNA showed only a reduced stimulatory activity on FACC transcription. <a href="#13" class="mim-tip-reference" title="Liebetrau, W., Budde, A., Savoia, A., Grummt, F., Hoehn, H. <strong>p53 activates Fanconi anemia group C gene expression.</strong> Hum. Molec. Genet. 6: 277-283, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9063748/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9063748</a>] [<a href="https://doi.org/10.1093/hmg/6.2.277" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9063748">Liebetrau et al. (1997)</a> concluded that the FACC gene can be added to the list of genes that interact with p53. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9063748" 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>Cells derived from FA patients are sensitive to crosslinking agents and have a prolonged G2 phase, suggesting a cell cycle abnormality. Transfection of type-C FA cells with the FAC cDNA corrects these cellular abnormalities. <a href="#12" class="mim-tip-reference" title="Kupfer, G. M., Yamashita, T., Naf, D., Suliman, A., Asano, S., D'Andrea, A. D. <strong>The Fanconi anemia polypeptide, FAC, binds to the cyclin-dependent kinase, cdc2.</strong> Blood 90: 1047-1054, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9242535/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9242535</a>]" pmid="9242535">Kupfer et al. (1997)</a> found that in synchronized HeLa cells, FAC protein expression increased during S phase, was maximal at the G2/M transition, and declined during M phase. In addition, the FAC protein coimmunoprecipitated with the cyclin-dependent kinase, cdc2. A patient-derived mutant FAC polypeptide, containing a point mutation at L554P (<a href="#0001">613899.0001</a>), failed to bind to cdc2. The FAC/cdc2 binding interaction therefore correlated with the functional activity of the FAC protein. Binding of FAC to cdc2 was mediated by the C-terminal 50 amino acids of FAC in a region of the protein required for FAC function. Taken together, these results suggested to <a href="#12" class="mim-tip-reference" title="Kupfer, G. M., Yamashita, T., Naf, D., Suliman, A., Asano, S., D'Andrea, A. D. <strong>The Fanconi anemia polypeptide, FAC, binds to the cyclin-dependent kinase, cdc2.</strong> Blood 90: 1047-1054, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9242535/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9242535</a>]" pmid="9242535">Kupfer et al. (1997)</a> that the binding of FAC and cdc2 is required for normal G2/M progression in mammalian cells. Absence of a functional interaction between FAC and cdc2 in FA cells may underlie the cell cycle abnormality and clinical abnormalities of FA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9242535" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Kupfer, G. M., Naf, D., Suliman, A., Pulsipher, M., D'Andrea, A. D. <strong>The Fanconi anaemia proteins, FAA and FAC, interact to form a nuclear complex.</strong> Nature Genet. 17: 487-490, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9398857/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9398857</a>] [<a href="https://doi.org/10.1038/ng1297-487" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9398857">Kupfer et al. (1997)</a> demonstrated that FAA (<a href="/entry/607139">607139</a>) and FAC bind each other and form a complex. Protein binding correlated with the functional activity of FAA and FAC, as patient-derived mutant FAC, L554P (<a href="#0001">613899.0001</a>), failed to bind FAA. Although unbound FAA and FAC localized predominantly to the cytoplasm, the FAA-FAC complex was found in similar abundance in both cytoplasm and nucleus. The results confirmed the interrelatedness of the FA genes in a pathway and suggested the cooperation of FAA and FAC in a nuclear function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9398857" 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="#3" class="mim-tip-reference" title="Garcia-Higuera, I., Kuang, Y., Naf, D., Wasik, J., D'Andrea, A. D. <strong>Fanconi anemia proteins FANCA, FANCC, and FANCG/XRCC9 interact in a functional nuclear complex.</strong> Molec. Cell. Biol. 19: 4866-4873, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10373536/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10373536</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10373536[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/10.1128/MCB.19.7.4866" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10373536">Garcia-Higuera et al. (1999)</a> determined that FANCG (<a href="/entry/602956">602956</a>) is required for binding between FANCA and FANCC and that all 3 proteins are components of a nuclear protein complex. Analysis of the protein interactions formed by lymphoblasts from each of the complementation groups suggested that the interaction between FANCA and FANCG is constitutive and is not regulated by FANCC or by the products of other FA genes. In contrast, the binding of FANCC required FANCA/FANCG binding and the products of other FA genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10373536" 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="Hoatlin, M. E., Christianson, T. A., Keeble, W. W., Hammond, A. T., Zhi, Y., Heinrich, M. C., Tower, P. A., Bagby, G. C., Jr. <strong>The Fanconi anemia group C gene product is located in both the nucleus and cytoplasm of human cells.</strong> Blood 91: 1418-1425, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9454773/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9454773</a>]" pmid="9454773">Hoatlin et al. (1998)</a> reproducibly detected approximately 10% of FAC protein in nuclear fractions. They concluded also that while the cytoplasmic localization of the FAC protein appears to be functionally important, the protein may also exert some essential nuclear function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9454773" 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>Activation of STAT1 (<a href="/entry/600555">600555</a>) in response to gamma-interferon (IFNG; <a href="/entry/147570">147570</a>) is suppressed in hematopoietic cells from children with FA-C. However, interferon regulatory factor-1 (IRF1; <a href="/entry/147575">147575</a>) is expressed at high levels in mutant FA-C cells (<a href="#21" class="mim-tip-reference" title="Parganas, E., Wang, D., Stravopodis, D., Topham, D. J., Marine, J.-C., Teglund, S., Vanin, E. F., Bodner, S., Colamonici, O. R., van Deursen, J. M., Grosveld, G., Ihle, J. N. <strong>Jak2 is essential for signaling through a variety of cytokine receptors.</strong> Cell 93: 385-395, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9590173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9590173</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81167-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9590173">Parganas et al., 1998</a>), suggesting that a non-STAT1 pathway is involved in constitutive activation of IRF1 in FA cells. In addition, hematopoietic cells from FA-C patients are hypersensitive to the apoptotic effects of IFNG. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9590173" 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="#20" class="mim-tip-reference" title="Pang, Q., Fagerlie, S., Christianson, T. A., Keeble, W., Faulkner, G., Diaz, J., Rathbun, R. K., Bagby, G. C. <strong>The Fanconi anemia protein FANCC binds to and facilitates the activation of STAT1 by gamma interferon and hematopoietic growth factors.</strong> Molec. Cell. Biol. 20: 4724-4735, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10848598/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10848598</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10848598[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/10.1128/MCB.20.13.4724-4735.2000" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10848598">Pang et al. (2000)</a> reported that in IFNG-stimulated FA-C cells, phosphorylation of JAK1 (<a href="/entry/147795">147795</a>), JAK2 (<a href="/entry/147796">147796</a>), and IFNG receptor-alpha (IFNGR1; <a href="/entry/107470">107470</a>) occurs normally, but STAT1 does not dock at the IFNGR1 chain, does not form nuclear DNA complexes, and does not induce the expression of IRF1. Expression of normal FANCC cDNA in mutant cells restored all of these normal functions of STAT1. Various cytokines stimulated the association of STAT1 with normal but not mutant (L554P) FANCC. <a href="#20" class="mim-tip-reference" title="Pang, Q., Fagerlie, S., Christianson, T. A., Keeble, W., Faulkner, G., Diaz, J., Rathbun, R. K., Bagby, G. C. <strong>The Fanconi anemia protein FANCC binds to and facilitates the activation of STAT1 by gamma interferon and hematopoietic growth factors.</strong> Molec. Cell. Biol. 20: 4724-4735, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10848598/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10848598</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10848598[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/10.1128/MCB.20.13.4724-4735.2000" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10848598">Pang et al. (2000)</a> proposed that hematopoietic defects in FA derive, at least in part, from an imbalance between mitogenic cues (due to reduced transduction of signals through growth factor receptors that activate STAT1) and mitogenic inhibitory cues (due to FANCC-dependent, STAT1-independent constitutive activation of mitotic inhibitory factors, such as IRF1). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10848598" 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="#19" class="mim-tip-reference" title="Pang, Q., Christianson, T. A., Keeble, W., Diaz, J., Faulkner, G. R., Reifsteck, C., Olson, S., Bagby, G. C. <strong>The Fanconi anemia complementation group C gene product: structural evidence of multifunctionality.</strong> Blood 98: 1392-1401, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11520787/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11520787</a>] [<a href="https://doi.org/10.1182/blood.v98.5.1392" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11520787">Pang et al. (2001)</a> presented evidence that a central, highly conserved domain of FANCC is required for functional interaction with STAT1 and that structural elements required for STAT1-related functions differ from those required for genotoxic responses to crosslinking agents. They commented that preservation of signaling capacity of cells bearing the 322delG mutation (<a href="#0007">613899.0007</a>) may account for the reduced severity and later onset of bone marrow failure associated with this mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11520787" 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="#2" class="mim-tip-reference" title="Donahue, S. L., Campbell, C. <strong>A DNA double strand break repair defect in Fanconi anemia fibroblasts.</strong> J. Biol. Chem. 277: 46243-46247, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12361951/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12361951</a>] [<a href="https://doi.org/10.1074/jbc.M207937200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12361951">Donahue and Campbell (2002)</a> found that fibroblasts from FA patients from complementation groups A, C, D2 (<a href="/entry/613984">613984</a>), and G were hypersensitive to restriction enzyme-induced cell death following electroporation of restriction enzymes. These fibroblasts also showed reduced efficiency in plasmid end-joining activity. Normal sensitivity and activity were restored following retrovirus mediated expression of the respective FA cDNAs. <a href="#2" class="mim-tip-reference" title="Donahue, S. L., Campbell, C. <strong>A DNA double strand break repair defect in Fanconi anemia fibroblasts.</strong> J. Biol. Chem. 277: 46243-46247, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12361951/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12361951</a>] [<a href="https://doi.org/10.1074/jbc.M207937200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12361951">Donahue and Campbell (2002)</a> also found that the L554P FANCC allele has dominant-negative activity. A fibrosarcoma cell line overexpressing this mutation showed significantly diminished efficiency in rejoining cohesive-ended and blunt-ended linearized plasmids and were hypersensitive to restriction enzyme-induced cell death. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12361951" 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>The Fanconi anemia nuclear complex (composed of the FA proteins A, C, G and F) is essential for protection against chromosome breakage. It activates the downstream protein FANCD2 by monoubiquitylation; this then forges an association with the BRCA1 (<a href="/entry/113705">113705</a>) protein at sites of DNA damage. <a href="#17" class="mim-tip-reference" title="Pace, P., Johnson, M., Tan, W. M., Mosedale, G., Sng, C., Hoatlin, M., de Winter, J., Joenje, H., Gergely, F., Patel, K. J. <strong>FANCE: the link between Fanconi anaemia complex assembly and activity.</strong> EMBO J. 21: 3414-3423, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12093742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12093742</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12093742[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/emboj/cdf355" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12093742">Pace et al. (2002)</a> showed that the FANCE (<a href="/entry/613976">613976</a>) protein is part of this nuclear complex, binding both FANCC and FANCD2. Indeed, FANCE is required for the nuclear accumulation of FANCC and provides a critical bridge between the FA complex and FANCD2. Disease-associated FANCC mutants do not bind to FANCE, cannot accumulate in the nucleus and are unable to prevent chromosome breakage. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12093742" 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="#22" class="mim-tip-reference" title="Pichierri, P., Averbeck, D., Rosselli, F. <strong>DNA cross-link-dependent RAD50/MRE11/NBS1 subnuclear assembly requires the Fanconi anemia C protein.</strong> Hum. Molec. Genet. 11: 2531-2546, 2002. Note: Erratum: Hum. Molec. Genet. 13: 1289 only, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12354779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12354779</a>] [<a href="https://doi.org/10.1093/hmg/11.21.2531" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12354779">Pichierri et al. (2002)</a> studied the assembly and activation of the RMN (RAD50, <a href="/entry/604040">604040</a>/MRE11, <a href="/entry/600814">600814</a>/NBS1, <a href="/entry/602667">602667</a>) complex by exposing cultured cells to the chemical interstrand crosslink inducers mitomycin C and photoactivated 8-methoxypsoralen. The authors determined that FA cells were unable to form subnuclear RMN foci in response to either interstrand crosslink inducer. In particular, mitomycin C-treated FANCC cells formed double-strand breaks and unhooked mitomycin C-induced interstrand crosslink similarly to FANCC wildtype cells. Additionally, the authors showed that the formation of foci, including BRCA1 (<a href="/entry/113705">113705</a>) and/or RAD51 (<a href="/entry/179617">179617</a>) proteins, was significantly delayed in FA cells. The authors concluded that FANCC may play a direct role in RMN focus assembly in response to interstrand crosslink inducers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12354779" 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 coimmunoprecipitation of HeLa cell nuclear extracts, <a href="#15" class="mim-tip-reference" title="Meetei, A. R., Sechi, S., Wallisch, M., Yang, D., Young, M. K., Joenje, H., Hoatlin, M. E., Wang, W. <strong>A multiprotein nuclear complex connects Fanconi anemia and Bloom syndrome.</strong> Molec. Cell. Biol. 23: 3417-3426, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12724401/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12724401</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12724401[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/10.1128/MCB.23.10.3417-3426.2003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12724401">Meetei et al. (2003)</a> identified 3 distinct multiprotein complexes associated with BLM (RECQL3; <a href="/entry/604610">604610</a>). One of the complexes, designated BRAFT, contained the Fanconi anemia core complementation group proteins FANCA, FANCG, FANCC, FANCE, and FANCF (<a href="/entry/613897">613897</a>), as well as topoisomerase III-alpha (TOP3A; <a href="/entry/601243">601243</a>) and replication protein A (RPA; see <a href="/entry/179835">179835</a>). BLM complexes isolated from an FA cell line had a lower molecular mass, likely due to loss of FANCA and other FA components. BLM- and FANCA-associated complexes had DNA unwinding activity, and BLM was required for this activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12724401" 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="#44" class="mim-tip-reference" title="Zhang, X., Li, J., Sejas, D. P., Rathbun, K. R., Bagby, G. C., Pang, Q. <strong>The Fanconi anemia proteins functionally interact with the protein kinase regulated by RNA (PKR).</strong> J. Biol. Chem. 279: 43910-43919, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15299030/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15299030</a>] [<a href="https://doi.org/10.1074/jbc.M403884200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15299030">Zhang et al. (2004)</a> used immunoprecipitation and reconstituted kinase assays to show that the FANCC, FANCA, and FANCG proteins functionally interacted with and inhibited the proapoptotic kinase PKR (<a href="/entry/176871">176871</a>), a kinase that represses translation when activated. PKR showed strongest binding to the FANCC protein. PKR activity was increased in bone marrow cells of patients with Fanconi anemia with mutations in the FANCC, FANCA, and FANCG genes. All 3 of these cell lines showed significant increases in PKR bound to the FANCC protein, which correlated with increased PKR activation. The cells also showed hypersensitivity to growth repression mediated by IFN-gamma and TNF-alpha (<a href="/entry/191160">191160</a>). Forced expression of a patient-derived FANCC mutation increased PKR activation and cell death. <a href="#44" class="mim-tip-reference" title="Zhang, X., Li, J., Sejas, D. P., Rathbun, K. R., Bagby, G. C., Pang, Q. <strong>The Fanconi anemia proteins functionally interact with the protein kinase regulated by RNA (PKR).</strong> J. Biol. Chem. 279: 43910-43919, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15299030/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15299030</a>] [<a href="https://doi.org/10.1074/jbc.M403884200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15299030">Zhang et al. (2004)</a> concluded that FA mutations cause increased binding of PKR to FANCC and increased PKR activation, leading to growth inhibition of hematopoietic progenitors and bone marrow failure in Fanconi anemia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15299030" 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="#18" class="mim-tip-reference" title="Pace, P., Mosedale, G., Hodskinson, M. R., Rosado, I. V. Sivasubramaniam, M., Patel, K. J. <strong>Ku70 corrupts DNA repair in the absence of the Fanconi anemia pathway.</strong> Science 329: 219-223, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20538911/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20538911</a>] [<a href="https://doi.org/10.1126/science.1192277" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20538911">Pace et al. (2010)</a> found a genetic interaction between the FANCC gene and the nonhomologous end joining (NHEJ) factor Ku70 (<a href="/entry/152690">152690</a>). Disruption of both FANCC and Ku70 suppressed sensitivity to crosslinking agents, diminished chromosome breaks, and reversed defective homologous recombination. Ku70 binds directly to free DNA ends, committing them to NHEJ repair. <a href="#18" class="mim-tip-reference" title="Pace, P., Mosedale, G., Hodskinson, M. R., Rosado, I. V. Sivasubramaniam, M., Patel, K. J. <strong>Ku70 corrupts DNA repair in the absence of the Fanconi anemia pathway.</strong> Science 329: 219-223, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20538911/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20538911</a>] [<a href="https://doi.org/10.1126/science.1192277" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20538911">Pace et al. (2010)</a> showed that purified FANCD2, a downstream effector of the Fanconi anemia pathway, might antagonize Ku70 activity by modifying such DNA substrates. <a href="#18" class="mim-tip-reference" title="Pace, P., Mosedale, G., Hodskinson, M. R., Rosado, I. V. Sivasubramaniam, M., Patel, K. J. <strong>Ku70 corrupts DNA repair in the absence of the Fanconi anemia pathway.</strong> Science 329: 219-223, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20538911/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20538911</a>] [<a href="https://doi.org/10.1126/science.1192277" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20538911">Pace et al. (2010)</a> concluded that these results reveal a function for the Fanconi anemia pathway in processing DNA ends, thereby diverting double-strand break repair from abortive NHEJ and toward homologous recombination. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20538911" 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="#1" class="mim-tip-reference" title="Chen, M., Tomkins, D. J., Auerbach, W., McKerlie, C., Youssoufian, H., Liu, L., Gan, O., Carreau, M., Auerbach, A., Groves, T., Guidos, C. J., Freedman, M. H., Cross, J., Percy, D. H., Dick, J. E., Joyner, A. L., Buchwald, M. <strong>Inactivation of Fac in mice produces inducible chromosomal instability and reduced fertility reminiscent of Fanconi anaemia.</strong> Nature Genet. 12: 448-451, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8630504/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8630504</a>] [<a href="https://doi.org/10.1038/ng0496-448" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8630504">Chen et al. (1996)</a> found that mice homozygous for a disrupted Fac gene did not show developmental abnormalities or hematologic defects during observations up to 9 months of age. However, their spleen cells had dramatically increased numbers of chromosomal aberrations in response to mitomycin C (MMC) and diepoxybutane. Homozygous male and female mice also had compromised gametogenesis, leading to markedly impaired fertility, a characteristic of Fanconi anemia patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8630504" 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="#37" class="mim-tip-reference" title="Whitney, M. A., Royle, G., Low, M. J., Kelly, M. A., Axthelm, M. K., Reifsteck, C., Olson, S., Braun, R. E., Heinrich, M. C., Rathbun, R. K., Bagby, G. C., Grompe, M. <strong>Germ cell defects and hematopoietic hypersensitivity to gamma-interferon in mice with a targeted disruption of the Fanconi anemia C gene.</strong> Blood 88: 49-58, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8704201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8704201</a>]" pmid="8704201">Whitney et al. (1996)</a> generated mice homozygous for a targeted deletion of exon 9 of the murine FA complementation group C gene. They selected this exon for knockout since there was evidence from mutation analysis in patients with FAC that the carboxy terminus of the protein is essential for its function. Mutant mice had normal neonatal viability and gross morphology. Their cells demonstrated chromosome breakage and crosslinker sensitivity. Male and female mutant mice had reduced numbers of germ cells and females had markedly impaired fertility. No anemia was detectable during the first year of life. The colony-forming capacity of bone marrow progenitor cells was abnormal and these cells were hypersensitive to gamma-interferon (<a href="/entry/147570">147570</a>). <a href="#37" class="mim-tip-reference" title="Whitney, M. A., Royle, G., Low, M. J., Kelly, M. A., Axthelm, M. K., Reifsteck, C., Olson, S., Braun, R. E., Heinrich, M. C., Rathbun, R. K., Bagby, G. C., Grompe, M. <strong>Germ cell defects and hematopoietic hypersensitivity to gamma-interferon in mice with a targeted disruption of the Fanconi anemia C gene.</strong> Blood 88: 49-58, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8704201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8704201</a>]" pmid="8704201">Whitney et al. (1996)</a> concluded that this abnormal sensitivity to gamma-interferon may form the basis for bone marrow failure in Fanconi anemia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8704201" 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="#23" class="mim-tip-reference" title="Pulliam-Leath, A. C., Ciccone, S. L., Nalepa, G., Li, X., Si, Y., Miravalle, L., Smith, D., Yuan, J., Li, J., Anur, P., Orazi, A., Vance, G. H., Yang, F.-C., Hanenberg, H., Bagby, G. C., Clapp, D. W. <strong>Genetic disruption of both Fancc and Fancg in mice recapitulates the hematopoietic manifestations of Fanconi anemia.</strong> Blood 116: 2915-2920, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20606166/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20606166</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20606166[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/10.1182/blood-2009-08-240747" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20606166">Pulliam-Leath et al. (2010)</a> found that Fancc -/-;Fancg -/- (<a href="/entry/602956">602956</a>) double-mutant mice developed spontaneous hematologic sequelae, including bone marrow failure, acute myeloid leukemia, myelodysplasia, and complex random chromosomal abnormalities, that Fancc -/- mice or Fancg -/- mice did not develop. Studies on cells derived from single-mutant mice showed that loss of Fancg resulted in a more severe defect in multiple hematopoietic compartments than loss of Fancc, suggesting that the 2 genes have nonoverlapping roles in hematopoiesis. However, both single- and double-mutant cells showed similar sensitivity to a DNA crosslinking agent. The phenotype of the double-mutant mice was most consistent with that of human patients with Fanconi anemia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20606166" 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="#24" class="mim-tip-reference" title="Rhee, D. B., Wang, Y., Mizesko, M., Zhou, F., Haneline, L., Liu, Y. <strong>FANCC suppresses short telomere-initiated telomere sister chromatid exchange.</strong> Hum. Molec. Genet. 19: 879-887, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20022886/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20022886</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20022886[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddp556" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20022886">Rhee et al. (2010)</a> studied the role of Fancc in telomere length regulation in mice. Deletion of Fancc did not affect telomerase activity, telomere length, or telomeric end-capping in a mouse strain possessing intrinsically long telomeres. However, ablation of Fancc did exacerbate telomere attrition when murine bone marrow cells experienced high cell turnover after serial transplantation. When Fancc-null mice were crossed into a telomerase reverse transcriptase (TERT; <a href="/entry/187270">187270</a>) heterozygous or null background (Tert +/- or Tert -/-) with short telomeres, Fancc deficiency led to an increase in the incidence of telomere sister chromatid exchange. In contrast, these phenotypes were not observed in Tert mutant mice with long telomeres. The authors concluded that Fancc deficiency accelerates telomere shortening during high turnover of hematopoietic cells and may promote telomere recombination initiated by short telomeres. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20022886" 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>.0001 FANCONI ANEMIA, COMPLEMENTATION GROUP C</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104886458 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104886458;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs104886458?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104886458" 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=rs104886458" 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=RCV000012823 OR RCV000058925 OR RCV001221431 OR RCV002399319 OR RCV003421917" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012823, RCV000058925, RCV001221431, RCV002399319, RCV003421917" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012823...</a>
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<p><a href="#30" class="mim-tip-reference" title="Strathdee, C. A., Gavish, H., Shannon, W. R., Buchwald, M. <strong>Cloning of cDNAs for Fanconi's anaemia by functional complementation.</strong> Nature 356: 763-767, 1992. Note: Erratum: Nature 358: 434 only, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1574115/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1574115</a>] [<a href="https://doi.org/10.1038/356763a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1574115">Strathdee et al. (1992)</a> and <a href="#4" class="mim-tip-reference" title="Gavish, H., dos Santos, C. C., Buchwald, M. <strong>Generation of a non-functional Fanconi anemia group C protein (FACC) by site-directed in vitro mutagenesis. (Abstract)</strong> Am. J. Hum. Genet. 51 (suppl.): A128 only, 1992."None>Gavish et al. (1992)</a> demonstrated that HSC536N cells, which represented the only confirmed Fanconi anemia cell line of complementation group C (FANCC; <a href="/entry/227645">227645</a>), have a T-to-C transition at base 1913 that changes codon 553 from leucine to proline (L553P). <a href="#5" class="mim-tip-reference" title="Gavish, H., dos Santos, C. C., Buchwald, M. <strong>A leu554-to-pro substitution completely abolishes the functional complementing activity of the Fanconi anemia (FACC) protein.</strong> Hum. Molec. Genet. 2: 123-126, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8499901/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8499901</a>] [<a href="https://doi.org/10.1093/hmg/2.2.123" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8499901">Gavish et al. (1993)</a> corrected the previously published FACC cDNA sequence which omitted 3 nucleotides. The corrected sequence predicts a 1,677-bp ORF and a protein of 558 amino acids. Therefore, the previously reported L553P mutation is, in fact, L554P. To avoid confusion, they chose to refer to the site of the mutation as base 1661, on the basis of the ORF, and amino acid 554 on the basis of its location in the protein. Using site-directed in vitro mutagenesis, <a href="#5" class="mim-tip-reference" title="Gavish, H., dos Santos, C. C., Buchwald, M. <strong>A leu554-to-pro substitution completely abolishes the functional complementing activity of the Fanconi anemia (FACC) protein.</strong> Hum. Molec. Genet. 2: 123-126, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8499901/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8499901</a>] [<a href="https://doi.org/10.1093/hmg/2.2.123" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8499901">Gavish et al. (1993)</a> demonstrated that the leu554-to-pro mutation completely abolishes the activity of the FACC protein as analyzed by functional complementation assay. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1574115+8499901" 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>The polypeptide encoded by the FAC gene binds to a group of cytoplasmic proteins in vitro and may form a multimeric complex. The leu554-to-pro mutant allele fails to correct the sensitivity of FA group C cells to mitomycin C. <a href="#41" class="mim-tip-reference" title="Youssoufian, H., Li, Y., Martin, M. E., Buchwald, M. <strong>Induction of Fanconi anemia cellular phenotype in human 293 cells by overexpression of a mutant FAC allele.</strong> J. Clin. Invest. 97: 957-962, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8613549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8613549</a>] [<a href="https://doi.org/10.1172/JCI118519" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8613549">Youssoufian et al. (1996)</a> reasoned that overexpression of the mutant protein in a wildtype cellular background might induce the FA phenotype by competing with endogenous FAC for binding to the accessory proteins. After stable transfection of human kidney 293 cells with wildtype and a mutant FAC allele containing the L554P substitution, 4 independent clones that expressed 4- to 15-fold higher levels of transcript from the mutant transgene relative to the endogenous FAC gene showed hypersensitivity to mitomycin C. By contrast, both parental and FAC-overexpressing cells maintained their relative resistance to mitomycin C. No differences in the biosynthesis, subcellular localization, and protein interactions of the normal and mutant proteins were detected. <a href="#41" class="mim-tip-reference" title="Youssoufian, H., Li, Y., Martin, M. E., Buchwald, M. <strong>Induction of Fanconi anemia cellular phenotype in human 293 cells by overexpression of a mutant FAC allele.</strong> J. Clin. Invest. 97: 957-962, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8613549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8613549</a>] [<a href="https://doi.org/10.1172/JCI118519" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8613549">Youssoufian et al. (1996)</a> stated that the induction of the FA phenotype in this system is compatible with the competition hypothesis and provides support for a functional role of the FAC-binding proteins in vivo. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8613549" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121917783 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121917783;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121917783?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121917783" 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=rs121917783" 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=RCV000012824 OR RCV000115356 OR RCV000471314 OR RCV000568180 OR RCV001356657 OR RCV004748517" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012824, RCV000115356, RCV000471314, RCV000568180, RCV001356657, RCV004748517" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012824...</a>
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<p>Using the BbvI restriction site change as a screening method, <a href="#8" class="mim-tip-reference" title="Gibson, R. A., Hajianpour, A., Buchwald, M., Mathew, C. G. <strong>Screening the FACC gene for mutations in patients with Fanconi anaemia. (Abstract)</strong> Am. J. Hum. Genet. 51 (suppl.): A216 only, 1992."None>Gibson et al. (1992)</a> found no instance of the L554P FANCC mutation (<a href="#0001">613899.0001</a>) in 38 unrelated patients with Fanconi anemia (FANCC; <a href="/entry/227645">227645</a>). However, they identified a truncated transcript that was shown to be due to a nonsense mutation changing arginine-185 to a stop codon (R185X). The mutation was a C-to-T transition at nucleotide 808.</p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104886456 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104886456;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs104886456?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104886456" 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=rs104886456" 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=RCV000012825 OR RCV000115354 OR RCV000197192 OR RCV000562912 OR RCV001358012 OR RCV004748518" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012825, RCV000115354, RCV000197192, RCV000562912, RCV001358012, RCV004748518" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012825...</a>
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<p>Using reverse transcription PCR and chemical mismatch cleavage (CMC), <a href="#38" class="mim-tip-reference" title="Whitney, M. A., Saito, H., Jakobs, P. M., Gibson, R. A., Moses, R. E., Grompe, M. <strong>A common mutation in the FACC gene causes Fanconi anaemia in Ashkenazi Jews.</strong> Nature Genet. 4: 202-205, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8348157/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8348157</a>] [<a href="https://doi.org/10.1038/ng0693-202" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8348157">Whitney et al. (1993)</a> demonstrated homozygosity for an identical splice mutation in the FANCC gene in 2 Ashkenazi Jewish patients with Fanconi anemia (FANCC; <a href="/entry/227645">227645</a>). Three additional patients bearing this allele were found through screening 21 other families. A single base change in the fourth intronic base changed the sequence from a consensus A to T, resulting in deletion of the 111-bp exon 4. They referred to the allele as IVS4+4, A-to-T. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8348157" 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="#36" class="mim-tip-reference" title="Whitney, M. A., Jakobs, P., Kaback, M., Moses, R. E., Grompe, M. <strong>The Ashkenazi Jewish Fanconi anemia mutation: incidence among patients and carrier frequency in the at-risk population.</strong> Hum. Mutat. 3: 339-341, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8081385/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8081385</a>] [<a href="https://doi.org/10.1002/humu.1380030402" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8081385">Whitney et al. (1994)</a> used allele-specific oligonucleotide hybridization to determine the frequency of this mutation in Ashkenazi Jews with Fanconi anemia (FA). They studied 11 patients, each of whom had 2 Jewish parents, and 1 patient who had a Jewish mother and a non-Jewish father. The mutation was found in 19 of the 23 Jewish FA chromosomes (83%), but was not found in 2 other Jewish patients, in 39 non-Jewish patients, or in 130 non-Jewish persons without FA. Two of 315 Jewish individuals without FA were found to be carriers of the mutation. <a href="#31" class="mim-tip-reference" title="Verlander, P. C., Kaporis, A., Liu, Q., Zhang, Q., Seligsohn, U., Auerbach, A. D. <strong>Carrier frequency of the IVS4 + 4 A-to-T mutation of the Fanconi anemia gene FAC in the Ashkenazi Jewish population.</strong> Blood 86: 4034-4038, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7492758/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7492758</a>]" pmid="7492758">Verlander et al. (1995)</a> developed amplification refractory mutation system (ARMS) assays for 5 known mutations in FAC and used these assays to determine the carrier frequency of the IVS4 +4 A-to-T mutation in an Ashkenazi Jewish population. Among 3,104 Jewish individuals, primarily of Ashkenazi descent, 35 IVS4 carriers were identified, for a carrier frequency of 1 in 89 (1.1%). Among 563 Iraqi Jews, no carriers of the IVS4 mutation were found. They suggested that a founder effect is responsible for the high frequency of the mutation in Ashkenazim and that the carrier frequency of more than 1% justified inclusion of this mutation in the battery of tests routinely provided to the Jewish population. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7492758+8081385" 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="#32" class="mim-tip-reference" title="Verlinsky, Y., Rechitsky, S., Schoolcraft, W., Strom, C., Kuliev, A. <strong>Preimplantation diagnosis for Fanconi anemia combined with HLA matching.</strong> JAMA 285: 3130-3133, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11427142/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11427142</a>] [<a href="https://doi.org/10.1001/jama.285.24.3130" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11427142">Verlinsky et al. (2001)</a> presented a means for guaranteeing HLA-matching tissues for stem cell transplantation. The advent of single-cell PCR provided the opportunity for combined preimplantation genetic diagnosis (PGD) and HLA antigen testing. They identified a couple, both carriers of the IVS4+4A-T mutation in the FANCC gene, with an affected child requiring an HLA-compatible donor for cord blood transplantation. They used DNA analysis of single blastomeres to preselect unaffected embryos representing an HLA match for the affected sib. The transfer of mutation-negative, HLA-compatible embryos resulted in the pregnancy and birth of an unaffected child. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11427142" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121917784 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121917784;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121917784?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121917784" 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=rs121917784" 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=RCV000012826 OR RCV000115351 OR RCV000476519 OR RCV001021181 OR RCV004748519" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012826, RCV000115351, RCV000476519, RCV001021181, RCV004748519" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012826...</a>
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<p>By mismatch analysis with chemical cleavage with osmium tetroxide and hydroxylamine, <a href="#16" class="mim-tip-reference" title="Murer-Orlando, M., Llerena, J. C., Jr., Birjandi, F., Gibson, R. A., Mathew, C. G. <strong>FACC gene mutations and early prenatal diagnosis of Fanconi's anaemia. (Letter)</strong> Lancet 342: 686 only, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8103176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8103176</a>] [<a href="https://doi.org/10.1016/0140-6736(93)91800-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8103176">Murer-Orlando et al. (1993)</a> demonstrated compound heterozygosity for a gln13-to-ter (Q13X) mutation in exon 1 of the FACC gene and an R548X mutation in exon 14 (<a href="#0005">613899.0005</a>) in chorionic villus samples obtained for prenatal diagnosis of Fanconi anemia of complementation group C (FANCC; <a href="/entry/227645">227645</a>). The 2 mutations were derived from the father and mother, respectively, and were also demonstrated in an affected sib. Chromosome breakage analysis on cultured chorionic cells had shown a higher response to diepoxybutane in the pregnancy at risk than in normal control samples. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8103176" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104886457 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104886457;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs104886457?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104886457" 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=rs104886457" 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=RCV000012827 OR RCV000058924 OR RCV000205197 OR RCV000572840" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012827, RCV000058924, RCV000205197, RCV000572840" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012827...</a>
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<p>For discussion of the arg548-to-ter (R548X) mutation in the FANCC gene that was found in compound heterozygous state in chorionic villus samples obtained for prenatal diagnosis of Fanconi anemia of complementation group C (FANCC; <a href="/entry/227645">227645</a>) by <a href="#16" class="mim-tip-reference" title="Murer-Orlando, M., Llerena, J. C., Jr., Birjandi, F., Gibson, R. A., Mathew, C. G. <strong>FACC gene mutations and early prenatal diagnosis of Fanconi's anaemia. (Letter)</strong> Lancet 342: 686 only, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8103176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8103176</a>] [<a href="https://doi.org/10.1016/0140-6736(93)91800-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8103176">Murer-Orlando et al. (1993)</a>, see <a href="#0004">613899.0004</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8103176" 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 FANCONI ANEMIA, COMPLEMENTATION GROUP C</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs794726667 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs794726667;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs794726667?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs794726667" 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=rs794726667" 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=RCV000012828 OR RCV001851810 OR RCV004619189 OR RCV004777561" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012828, RCV001851810, RCV004619189, RCV004777561" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012828...</a>
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<p><a href="#14" class="mim-tip-reference" title="Lo Ten Foe, J. R., Rooimans, M. A., Joenje, H., Arwert, F. <strong>Novel frameshift mutation (1806insA) in exon 14 of the Fanconi anemia C gene, FAC.</strong> Hum. Mutat. 7: 264-265, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8829660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8829660</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1996)7:3<264::AID-HUMU11>3.0.CO;2-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8829660">Lo Ten Foe et al. (1996)</a> described a frameshift mutation in the FANCC gene resulting from insertion of an adenine after nucleotide 1806 in exon 14. The insertion caused a frameshift that was expected to give rise to a truncated protein of 526 amino acids, which is shorter than the protein resulting from premature termination caused by the R548X mutation (<a href="#0005">613899.0005</a>), and therefore presumed to be inactive. Mutations in exon 14 are the most C-terminal of 7 pathogenic mutations that the authors discussed. Three pathogenic mutations are located in exon 14, suggesting that the C-terminal part of FAC protein is essential for an as yet unknown function. The other 2 exon 14 mutations reported to that time were L554P (<a href="#0001">613899.0001</a>) and R548X (<a href="#0005">613899.0005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8829660" 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 FANCONI ANEMIA, COMPLEMENTATION GROUP C</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104886459 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104886459;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs104886459?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104886459" 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=rs104886459" 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=RCV000012829 OR RCV000058926 OR RCV000460906 OR RCV001025667 OR RCV004748520" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012829, RCV000058926, RCV000460906, RCV001025667, RCV004748520" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012829...</a>
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<p>Mutations within the Fanconi anemia complementation group C (FAC) gene account for approximately 14% of diagnosed Fanconi anemia (FA; see <a href="/entry/227645">227645</a>) cases. Two mutations, one in exon 1 (322delG) and the other in exon 4 (IVS4+4A-T; <a href="#0003">613899.0003</a>), account for 90% of known FAC mutations. The 322delG mutation results in a mild FA phenotype, while the IVS4 donor splice site mutation results in a severe FA phenotype. To determine the molecular basis for this clinical variability, <a href="#40" class="mim-tip-reference" title="Yamashita, T., Wu, N., Kupfer, G., Corless, C., Joenje, H., Grompe, M., D'Andrea, A. D. <strong>Clinical variability of Fanconi anemia (type C) results from expression of an amino terminal truncated Fanconi anemia complementation group C polypeptide with partial activity.</strong> Blood 87: 4424-4432, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8639804/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8639804</a>]" pmid="8639804">Yamashita et al. (1996)</a> analyzed patient-derived cell lines for the expression of characteristic mutant FAC polypeptides. All cell lines with the 322delG mutation expressed a 50-kD FAC polypeptide, shown to be an N-terminal truncated isoform of FAC reinitiated at methionine 55. All cell lines with the IVS4 donor splice site mutation lacked FRP-50 (FAC-related protein). Overexpression of a cDNA encoding FRP-50 in a FAC cell line resulted in partial correction of mitomycin C sensitivity. Thus, expression of an N-terminal truncated FAC protein accounted, at least in part, for the clinical heterogeneity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8639804" 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="#19" class="mim-tip-reference" title="Pang, Q., Christianson, T. A., Keeble, W., Diaz, J., Faulkner, G. R., Reifsteck, C., Olson, S., Bagby, G. C. <strong>The Fanconi anemia complementation group C gene product: structural evidence of multifunctionality.</strong> Blood 98: 1392-1401, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11520787/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11520787</a>] [<a href="https://doi.org/10.1182/blood.v98.5.1392" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11520787">Pang et al. (2001)</a> observed that cells bearing the 322delG mutation, which preserves a conserved region of FANCC, showed normal STAT1 activation but remained hypersensitive to mitomycin C. Preservation of signaling capacity of cells bearing this mutation may account for the reduced severity and later onset of bone marrow failure associated with it. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11520787" 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 FANCONI ANEMIA, COMPLEMENTATION GROUP C</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121917785 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121917785;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=rs121917785" 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=rs121917785" 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=RCV000012830" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012830" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012830</a>
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<p>In a patient with Fanconi anemia of complementation group C (FANCC; <a href="/entry/227645">227645</a>) and his affected brother, <a href="#33" class="mim-tip-reference" title="Waisfisz, Q., Morgan, N. V., Savino, M., de Winter, J. P., van Berkel, C. G. M., Hoatlin, M. E., Ianzano, L., Gibson, R. A., Arwert, F., Savoia, A., Mathew, C. G., Pronk, J. C., Joenje, H. <strong>Spontaneous functional correction of homozygous Fanconi anaemia alleles reveals novel mechanistic basis for reverse mosaicism.</strong> Nature Genet. 22: 379-383, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10431244/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10431244</a>] [<a href="https://doi.org/10.1038/11956" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10431244">Waisfisz et al. (1999)</a> detected a homozygous 1749T-to-G missense mutation in the FANCC gene, predicting a change from leucine to arginine at codon 496 (L496R). Cytogenetic analysis revealed the patient and his brother to be mosaics with an additional de novo 1748C-to-T transition at 1 allele. The combination of the 2 mutations on 1 allele predicted a change from the mutant arginine to cysteine. Evaluation of the functional status of the proteins encoded by both alleles showed full correction by the cDNA with both mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10431244" 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">rs794726668 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs794726668;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=rs794726668" 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=rs794726668" 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=RCV000012831 OR RCV001221363 OR RCV001588811" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012831, RCV001221363, RCV001588811" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012831...</a>
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<p>In affected members of 2 unrelated but consanguineous families of Arabian ancestry with Fanconi anemia of complementation group C (FANCC; <a href="/entry/227645">227645</a>), <a href="#9" class="mim-tip-reference" title="Hartmann, L., Neveling, K., Borkens, S., Schneider, H., Freund, M., Grassman, E., Theiss, S., Wawer, A., Burdach, S., Auerbach, A. D., Schindler, D., Hanenberg, H., Schaal, H. <strong>Correct mRNA processing at a mutant TT splice donor in FANCC ameliorates the clinical phenotype in patients and is enhanced by delivery of suppressor U1 snRNAs.</strong> Am. J. Hum. Genet. 87: 480-493, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20869034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20869034</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20869034[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.2010.08.016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20869034">Hartmann et al. (2010)</a> identified a homozygous G-to-T transversion in intron 2 of the FANCC gene (165+1G-T), changing a highly conserved GT dinucleotide to TT at the 5-prime splice site. Two affected individuals from a family of mixed Arabian/British ancestry were compound heterozygous for the intron 2 mutation and a 250-bp deletion (<a href="#0010">613899.0010</a>), resulting in the skipping of exons 2 and 3. The phenotype was relatively mild in the 2 Arabian families, but was severe in the 2 patients in the mixed Arabian/British family, who died at ages 13.5 and 16 years. RT-PCR analysis of the splice site mutation yielded 4 distinct products, including the wildtype product at 27% of the total transcripts. Functional analysis of the splice site mutation within splicing reporters showed that increasing complementarity to U1 snRNA could reconstitute splicing at the noncanonical TT dinucleotide, and that artificial TT-adapted U1 snRNA improved correct mRNA processing at the mutant TT splice site. These results were replicated in patient fibroblasts, with correctly spliced transcripts increasing from about 30% to 56-58%. Finally, <a href="#9" class="mim-tip-reference" title="Hartmann, L., Neveling, K., Borkens, S., Schneider, H., Freund, M., Grassman, E., Theiss, S., Wawer, A., Burdach, S., Auerbach, A. D., Schindler, D., Hanenberg, H., Schaal, H. <strong>Correct mRNA processing at a mutant TT splice donor in FANCC ameliorates the clinical phenotype in patients and is enhanced by delivery of suppressor U1 snRNAs.</strong> Am. J. Hum. Genet. 87: 480-493, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20869034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20869034</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20869034[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.2010.08.016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20869034">Hartmann et al. (2010)</a> demonstrated that use of lentiviral vectors as a delivery system to introduce expression cassettes for TT-adapted U1 snRNAs into primary FANCC patient fibroblasts allowed the continuous correction of the DNA damage-induced G2 cell-cycle arrest in these cells. These findings indicated an alternative transcript-targeting approach for genetic therapy of inherited splice site mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20869034" 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>.0010 FANCONI ANEMIA, COMPLEMENTATION GROUP C</strong>
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FANCC, 250-BP DEL
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012832" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012832" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012832</a>
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<p>For discussion of the 250-bp deletion in the FANCC gene that was found in compound heterozygous state in patients with Fanconi anemia of complementation group C (FANCC; <a href="/entry/227645">227645</a>) by <a href="#9" class="mim-tip-reference" title="Hartmann, L., Neveling, K., Borkens, S., Schneider, H., Freund, M., Grassman, E., Theiss, S., Wawer, A., Burdach, S., Auerbach, A. D., Schindler, D., Hanenberg, H., Schaal, H. <strong>Correct mRNA processing at a mutant TT splice donor in FANCC ameliorates the clinical phenotype in patients and is enhanced by delivery of suppressor U1 snRNAs.</strong> Am. J. Hum. Genet. 87: 480-493, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20869034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20869034</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20869034[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.2010.08.016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20869034">Hartmann et al. (2010)</a>, see <a href="#0009">613899.0009</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20869034" 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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|
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|
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<a id="1" class="mim-anchor"></a>
|
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<a id="Chen1996" class="mim-anchor"></a>
|
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|
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Chen, M., Tomkins, D. J., Auerbach, W., McKerlie, C., Youssoufian, H., Liu, L., Gan, O., Carreau, M., Auerbach, A., Groves, T., Guidos, C. J., Freedman, M. H., Cross, J., Percy, D. H., Dick, J. E., Joyner, A. L., Buchwald, M.
|
|
<strong>Inactivation of Fac in mice produces inducible chromosomal instability and reduced fertility reminiscent of Fanconi anaemia.</strong>
|
|
Nature Genet. 12: 448-451, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8630504/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8630504</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8630504" 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/ng0496-448" target="_blank">Full Text</a>]
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|
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|
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|
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Donahue, S. L., Campbell, C.
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<strong>A DNA double strand break repair defect in Fanconi anemia fibroblasts.</strong>
|
|
J. Biol. Chem. 277: 46243-46247, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12361951/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12361951</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12361951" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.M207937200" target="_blank">Full Text</a>]
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Garcia-Higuera, I., Kuang, Y., Naf, D., Wasik, J., D'Andrea, A. D.
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<strong>Fanconi anemia proteins FANCA, FANCC, and FANCG/XRCC9 interact in a functional nuclear complex.</strong>
|
|
Molec. Cell. Biol. 19: 4866-4873, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10373536/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10373536</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10373536[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=10373536" 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/10.1128/MCB.19.7.4866" target="_blank">Full Text</a>]
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|
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Gavish, H., dos Santos, C. C., Buchwald, M.
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<strong>Generation of a non-functional Fanconi anemia group C protein (FACC) by site-directed in vitro mutagenesis. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 51 (suppl.): A128 only, 1992.
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Gavish, H., dos Santos, C. C., Buchwald, M.
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<strong>A leu554-to-pro substitution completely abolishes the functional complementing activity of the Fanconi anemia (FACC) protein.</strong>
|
|
Hum. Molec. Genet. 2: 123-126, 1993.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8499901/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8499901</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8499901" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/2.2.123" target="_blank">Full Text</a>]
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Gibson, R. A., Buchwald, M., Roberts, R. G., Mathew, C. G.
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<strong>Characterisation of the exon structure of the Fanconi anaemia group C gene by vectorette PCR.</strong>
|
|
Hum. Molec. Genet. 2: 35-38, 1993.
|
|
|
|
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|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8490620/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8490620</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8490620" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/2.1.35" target="_blank">Full Text</a>]
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Gibson, R. A., Ford, D., Jansen, S., Savoia, A., Havenga, C., Milner, R. D., de Ravel, T. J., Cohn, R. J., Ball, S. E., Roberts, I., Llerena, J. C., Vorechovsky, I., Pearson, T., Birjandi, F., Hussein, S. S., Murer-Orlando, M., Easton, D. F., Mathew, C. G.
|
|
<strong>Genetic mapping of the FACC gene and linkage analysis in Fanconi anaemia families.</strong>
|
|
J. Med. Genet. 31: 868-871, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7853372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7853372</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7853372" 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.31.11.868" target="_blank">Full Text</a>]
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|
|
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|
|
|
<li>
|
|
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|
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|
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Gibson, R. A., Hajianpour, A., Buchwald, M., Mathew, C. G.
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|
<strong>Screening the FACC gene for mutations in patients with Fanconi anaemia. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 51 (suppl.): A216 only, 1992.
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|
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</li>
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|
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Hartmann, L., Neveling, K., Borkens, S., Schneider, H., Freund, M., Grassman, E., Theiss, S., Wawer, A., Burdach, S., Auerbach, A. D., Schindler, D., Hanenberg, H., Schaal, H.
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<strong>Correct mRNA processing at a mutant TT splice donor in FANCC ameliorates the clinical phenotype in patients and is enhanced by delivery of suppressor U1 snRNAs.</strong>
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Am. J. Hum. Genet. 87: 480-493, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20869034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20869034</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20869034[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=20869034" 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.2010.08.016" target="_blank">Full Text</a>]
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|
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<a id="Hoatlin1998" class="mim-anchor"></a>
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|
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Hoatlin, M. E., Christianson, T. A., Keeble, W. W., Hammond, A. T., Zhi, Y., Heinrich, M. C., Tower, P. A., Bagby, G. C., Jr.
|
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<strong>The Fanconi anemia group C gene product is located in both the nucleus and cytoplasm of human cells.</strong>
|
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Blood 91: 1418-1425, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9454773/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9454773</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9454773" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="Kupfer1997" class="mim-anchor"></a>
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Kupfer, G. M., Naf, D., Suliman, A., Pulsipher, M., D'Andrea, A. D.
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<strong>The Fanconi anaemia proteins, FAA and FAC, interact to form a nuclear complex.</strong>
|
|
Nature Genet. 17: 487-490, 1997.
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9398857/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9398857</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9398857" 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/ng1297-487" target="_blank">Full Text</a>]
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Kupfer, G. M., Yamashita, T., Naf, D., Suliman, A., Asano, S., D'Andrea, A. D.
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<strong>The Fanconi anemia polypeptide, FAC, binds to the cyclin-dependent kinase, cdc2.</strong>
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Blood 90: 1047-1054, 1997.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9242535/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9242535</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9242535" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Liebetrau1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Liebetrau, W., Budde, A., Savoia, A., Grummt, F., Hoehn, H.
|
|
<strong>p53 activates Fanconi anemia group C gene expression.</strong>
|
|
Hum. Molec. Genet. 6: 277-283, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9063748/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9063748</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9063748" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/6.2.277" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Lo Ten Foe1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lo Ten Foe, J. R., Rooimans, M. A., Joenje, H., Arwert, F.
|
|
<strong>Novel frameshift mutation (1806insA) in exon 14 of the Fanconi anemia C gene, FAC.</strong>
|
|
Hum. Mutat. 7: 264-265, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8829660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8829660</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8829660" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/(SICI)1098-1004(1996)7:3<264::AID-HUMU11>3.0.CO;2-0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Meetei2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Meetei, A. R., Sechi, S., Wallisch, M., Yang, D., Young, M. K., Joenje, H., Hoatlin, M. E., Wang, W.
|
|
<strong>A multiprotein nuclear complex connects Fanconi anemia and Bloom syndrome.</strong>
|
|
Molec. Cell. Biol. 23: 3417-3426, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12724401/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12724401</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12724401[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=12724401" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1128/MCB.23.10.3417-3426.2003" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Murer-Orlando1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Murer-Orlando, M., Llerena, J. C., Jr., Birjandi, F., Gibson, R. A., Mathew, C. G.
|
|
<strong>FACC gene mutations and early prenatal diagnosis of Fanconi's anaemia. (Letter)</strong>
|
|
Lancet 342: 686 only, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8103176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8103176</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8103176" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0140-6736(93)91800-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Pace2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pace, P., Johnson, M., Tan, W. M., Mosedale, G., Sng, C., Hoatlin, M., de Winter, J., Joenje, H., Gergely, F., Patel, K. J.
|
|
<strong>FANCE: the link between Fanconi anaemia complex assembly and activity.</strong>
|
|
EMBO J. 21: 3414-3423, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12093742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12093742</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12093742[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=12093742" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/emboj/cdf355" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Pace2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pace, P., Mosedale, G., Hodskinson, M. R., Rosado, I. V. Sivasubramaniam, M., Patel, K. J.
|
|
<strong>Ku70 corrupts DNA repair in the absence of the Fanconi anemia pathway.</strong>
|
|
Science 329: 219-223, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20538911/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20538911</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20538911" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1192277" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Pang2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pang, Q., Christianson, T. A., Keeble, W., Diaz, J., Faulkner, G. R., Reifsteck, C., Olson, S., Bagby, G. C.
|
|
<strong>The Fanconi anemia complementation group C gene product: structural evidence of multifunctionality.</strong>
|
|
Blood 98: 1392-1401, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11520787/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11520787</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11520787" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood.v98.5.1392" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Pang2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pang, Q., Fagerlie, S., Christianson, T. A., Keeble, W., Faulkner, G., Diaz, J., Rathbun, R. K., Bagby, G. C.
|
|
<strong>The Fanconi anemia protein FANCC binds to and facilitates the activation of STAT1 by gamma interferon and hematopoietic growth factors.</strong>
|
|
Molec. Cell. Biol. 20: 4724-4735, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10848598/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10848598</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10848598[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=10848598" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1128/MCB.20.13.4724-4735.2000" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Parganas1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Parganas, E., Wang, D., Stravopodis, D., Topham, D. J., Marine, J.-C., Teglund, S., Vanin, E. F., Bodner, S., Colamonici, O. R., van Deursen, J. M., Grosveld, G., Ihle, J. N.
|
|
<strong>Jak2 is essential for signaling through a variety of cytokine receptors.</strong>
|
|
Cell 93: 385-395, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9590173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9590173</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9590173" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0092-8674(00)81167-8" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Pichierri2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pichierri, P., Averbeck, D., Rosselli, F.
|
|
<strong>DNA cross-link-dependent RAD50/MRE11/NBS1 subnuclear assembly requires the Fanconi anemia C protein.</strong>
|
|
Hum. Molec. Genet. 11: 2531-2546, 2002. Note: Erratum: Hum. Molec. Genet. 13: 1289 only, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12354779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12354779</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12354779" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/11.21.2531" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Pulliam-Leath2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pulliam-Leath, A. C., Ciccone, S. L., Nalepa, G., Li, X., Si, Y., Miravalle, L., Smith, D., Yuan, J., Li, J., Anur, P., Orazi, A., Vance, G. H., Yang, F.-C., Hanenberg, H., Bagby, G. C., Clapp, D. W.
|
|
<strong>Genetic disruption of both Fancc and Fancg in mice recapitulates the hematopoietic manifestations of Fanconi anemia.</strong>
|
|
Blood 116: 2915-2920, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20606166/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20606166</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20606166[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=20606166" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood-2009-08-240747" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Rhee2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rhee, D. B., Wang, Y., Mizesko, M., Zhou, F., Haneline, L., Liu, Y.
|
|
<strong>FANCC suppresses short telomere-initiated telomere sister chromatid exchange.</strong>
|
|
Hum. Molec. Genet. 19: 879-887, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20022886/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20022886</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20022886[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=20022886" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddp556" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Riley1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Riley, J., Butler, R., Ogilvie, D., Finniear, R., Jenner, D., Powell, S., Anand, R., Smith, J. C., Markham, A. F.
|
|
<strong>A novel, rapid method for the isolation of terminal sequences from yeast artificial chromosome (YAC) clones.</strong>
|
|
Nucleic Acids Res. 18: 2887-2890, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2161516/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2161516</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2161516" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/nar/18.10.2887" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Roberts1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Roberts, R. G., Coffey, A. J., Bobrow, M., Bentley, D. R.
|
|
<strong>Determination of the exon structure of the distal portion of the dystrophin gene by vectorette PCR.</strong>
|
|
Genomics 13: 942-950, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1505985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1505985</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1505985" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0888-7543(92)90005-d" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Savoia1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Savoia, A., Centra, M., Ianzano, L., de Cillis, G. P., Zelante, L., Buchwald, M.
|
|
<strong>Characterization of the 5-prime region of the Fanconi anaemia group C (FACC) gene.</strong>
|
|
Hum. Molec. Genet. 4: 1321-1326, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7581369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7581369</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7581369" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/4.8.1321" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Segal1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Segal, G. M., Magenis, R. E., Brown, M., Keeble, W., Smith, T. D., Heinrich, M. C., Bagby, G. C., Jr.
|
|
<strong>Repression of Fanconi anemia gene (FACC) expression inhibits growth of hematopoietic progenitor cells.</strong>
|
|
J. Clin. Invest. 94: 846-852, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7518843/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7518843</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7518843" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI117405" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Strathdee1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Strathdee, C. A., Duncan, A. M. V., Buchwald, M.
|
|
<strong>Evidence for at least four Fanconi anaemia genes including FACC on chromosome 9.</strong>
|
|
Nature Genet. 1: 196-198, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1303234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1303234</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1303234" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng0692-196" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Strathdee1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Strathdee, C. A., Gavish, H., Shannon, W. R., Buchwald, M.
|
|
<strong>Cloning of cDNAs for Fanconi's anaemia by functional complementation.</strong>
|
|
Nature 356: 763-767, 1992. Note: Erratum: Nature 358: 434 only, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1574115/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1574115</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1574115" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/356763a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Verlander1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Verlander, P. C., Kaporis, A., Liu, Q., Zhang, Q., Seligsohn, U., Auerbach, A. D.
|
|
<strong>Carrier frequency of the IVS4 + 4 A-to-T mutation of the Fanconi anemia gene FAC in the Ashkenazi Jewish population.</strong>
|
|
Blood 86: 4034-4038, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7492758/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7492758</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7492758" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Verlinsky2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Verlinsky, Y., Rechitsky, S., Schoolcraft, W., Strom, C., Kuliev, A.
|
|
<strong>Preimplantation diagnosis for Fanconi anemia combined with HLA matching.</strong>
|
|
JAMA 285: 3130-3133, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11427142/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11427142</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11427142" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1001/jama.285.24.3130" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Waisfisz1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Waisfisz, Q., Morgan, N. V., Savino, M., de Winter, J. P., van Berkel, C. G. M., Hoatlin, M. E., Ianzano, L., Gibson, R. A., Arwert, F., Savoia, A., Mathew, C. G., Pronk, J. C., Joenje, H.
|
|
<strong>Spontaneous functional correction of homozygous Fanconi anaemia alleles reveals novel mechanistic basis for reverse mosaicism.</strong>
|
|
Nature Genet. 22: 379-383, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10431244/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10431244</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10431244" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/11956" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Wevrick1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wevrick, R., Barker, J. E., Eppig, J. T., Nadeau, J. H., Buchwald, M.
|
|
<strong>Expression of the Fanconi anemia group C gene in the mouse. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 51 (suppl.): A137 only, 1992.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Wevrick1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wevrick, R., Barker, J. E., Nadeau, J. H., Szpirer, C., Buchwald, M.
|
|
<strong>Mapping of the murine and rat Facc genes and assessment of flexed-tail as a candidate mouse homolog of Fanconi anemia group C.</strong>
|
|
Mammalian Genome 4: 440-444, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7690622/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7690622</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7690622" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF00296818" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Whitney1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Whitney, M. A., Jakobs, P., Kaback, M., Moses, R. E., Grompe, M.
|
|
<strong>The Ashkenazi Jewish Fanconi anemia mutation: incidence among patients and carrier frequency in the at-risk population.</strong>
|
|
Hum. Mutat. 3: 339-341, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8081385/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8081385</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8081385" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.1380030402" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Whitney1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Whitney, M. A., Royle, G., Low, M. J., Kelly, M. A., Axthelm, M. K., Reifsteck, C., Olson, S., Braun, R. E., Heinrich, M. C., Rathbun, R. K., Bagby, G. C., Grompe, M.
|
|
<strong>Germ cell defects and hematopoietic hypersensitivity to gamma-interferon in mice with a targeted disruption of the Fanconi anemia C gene.</strong>
|
|
Blood 88: 49-58, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8704201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8704201</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8704201" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Whitney1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Whitney, M. A., Saito, H., Jakobs, P. M., Gibson, R. A., Moses, R. E., Grompe, M.
|
|
<strong>A common mutation in the FACC gene causes Fanconi anaemia in Ashkenazi Jews.</strong>
|
|
Nature Genet. 4: 202-205, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8348157/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8348157</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8348157" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng0693-202" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" class="mim-anchor"></a>
|
|
<a id="Yamashita1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yamashita, T., Barber, D. L., Zhu, Y., Wu, N., D'Andrea, A. D.
|
|
<strong>The Fanconi anemia polypeptide FACC is localized to the cytoplasm.</strong>
|
|
Proc. Nat. Acad. Sci. 91: 6712-6716, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7517562/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7517562</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7517562" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.91.14.6712" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Yamashita1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yamashita, T., Wu, N., Kupfer, G., Corless, C., Joenje, H., Grompe, M., D'Andrea, A. D.
|
|
<strong>Clinical variability of Fanconi anemia (type C) results from expression of an amino terminal truncated Fanconi anemia complementation group C polypeptide with partial activity.</strong>
|
|
Blood 87: 4424-4432, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8639804/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8639804</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8639804" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
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|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="41" class="mim-anchor"></a>
|
|
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|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Youssoufian, H., Li, Y., Martin, M. E., Buchwald, M.
|
|
<strong>Induction of Fanconi anemia cellular phenotype in human 293 cells by overexpression of a mutant FAC allele.</strong>
|
|
J. Clin. Invest. 97: 957-962, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8613549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8613549</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8613549" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI118519" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
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|
|
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|
|
|
|
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|
|
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|
|
<a id="Youssoufian1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
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|
|
Youssoufian, H.
|
|
<strong>Localization of Fanconi anemia C protein to the cytoplasm of mammalian cells.</strong>
|
|
Proc. Nat. Acad. Sci. 91: 7975-7979, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8058745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8058745</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8058745" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
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[<a href="https://doi.org/10.1073/pnas.91.17.7975" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
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|
|
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|
|
|
|
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|
|
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|
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|
|
<div class="">
|
|
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|
|
Youssoufian, H.
|
|
<strong>Cytoplasmic localization of FAC is essential for the correction of a prerepair defect in Fanconi anemia group C cells.</strong>
|
|
J. Clin. Invest. 97: 2003-2010, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8621788/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8621788</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8621788" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
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|
|
|
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[<a href="https://doi.org/10.1172/JCI118635" target="_blank">Full Text</a>]
|
|
|
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|
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|
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|
|
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|
|
|
|
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|
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<a id="Zhang2004" class="mim-anchor"></a>
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|
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|
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Zhang, X., Li, J., Sejas, D. P., Rathbun, K. R., Bagby, G. C., Pang, Q.
|
|
<strong>The Fanconi anemia proteins functionally interact with the protein kinase regulated by RNA (PKR).</strong>
|
|
J. Biol. Chem. 279: 43910-43919, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15299030/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15299030</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15299030" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.M403884200" target="_blank">Full Text</a>]
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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George E. Tiller - updated : 11/8/2011
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 6/13/2011
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Anne M. Stumpf : 4/14/2011
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alopez : 11/07/2019
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mcolton : 06/15/2015<br>terry : 4/4/2013<br>terry : 6/20/2012<br>alopez : 11/10/2011<br>terry : 11/8/2011<br>carol : 7/8/2011<br>wwang : 6/24/2011<br>ckniffin : 6/13/2011<br>alopez : 4/19/2011<br>alopez : 4/19/2011
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<strong>*</strong> 613899
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FANCC GENE; FANCC
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<em>Alternative titles; symbols</em>
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FAC; FACC
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<strong><em>HGNC Approved Gene Symbol: FANCC</em></strong>
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<strong>SNOMEDCT:</strong> 1285021005;
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Cytogenetic location: 9q22.32
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Genomic coordinates <span class="small">(GRCh38)</span> : 9:95,099,054-95,317,709 </span>
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<span class="small">(from NCBI)</span>
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<strong>Gene-Phenotype Relationships</strong>
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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9q22.32
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Fanconi anemia, complementation group C
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227645
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Autosomal recessive
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3
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<strong>TEXT</strong>
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<strong>Description</strong>
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<p>The FANCC gene is one of a group of classical Fanconi anemia genes whose protein products physically interact in a multiprotein core complex. The main function of this core complex with E3 ubiquitin ligase activity appears to be the posttranslational activations of FANCD2 (613984) and FANCI (611360) by monoubiquitination of specific lysine residues (summary by Hartmann et al., 2010). </p>
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<strong>Cloning and Expression</strong>
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<p>Using a functional complementation method, Strathdee et al. (1992) cloned cDNAs that corrected the defect of Fanconi anemia group C cells. The cDNAs encoded alternatively processed transcripts of a new gene, designated FACC, mutated in patients with Fanconi anemia complementation group C. FACC transcripts were detected in a wide variety of tissues and cell lines by use of PCR with reverse-transcribed RNA. </p><p>Gavish et al. (1993) corrected the previously published FACC cDNA sequence which omitted 3 nucleotides. The corrected sequence predicts a 1,677-bp ORF and a protein of 558 amino acids. </p><p>Wevrick et al. (1992) cloned cDNAs corresponding to the mouse Facc gene. The sequence of the human and mouse proteins are 81% identical. The mouse gene encodes a protein of 558 amino acids, compared to 557 amino acids in the human protein.</p>
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<strong>Gene Structure</strong>
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<p>Gibson et al. (1993) isolated a YAC clone containing the FACC gene and used vectorette PCR to determine that the gene contains 14 exons. (Vectorette PCR was illustrated by their Figure 1. It was performed according to the method of Riley et al. (1990), described in detail by Roberts et al. (1992).) </p><p>Several different forms of FACC mRNA that share the same coding region have been isolated. At least 2 species result from the use of alternative exons at the 5-prime end, and 3 result from the use of distinct polyadenylation signals. Savoia et al. (1995) isolated genomic clones corresponding to the 5-prime region, including a putative promoter and 2 alternate 5-prime exons. These exons, which they referred to as exons -1 and -1a, were found to be separated by a small intron, with exon -1 located 5-prime to the exon -1a. Further, these exons were flanked by consensus sequences of donor sites at the 5-prime ends of introns. An acceptor splice site was not evident 5-prime of exon -1a, suggesting that exon -1 is not spliced onto exon -1a. The sequences upstream of exon -1 and -1a had no obvious TATA or CAAT boxes but included CG-rich sequences. Savoia et al. (1995) suggested that mutations affecting the 5-prime UTR and the promoter region may underlie some cases of Fanconi anemia. </p>
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<strong>Mapping</strong>
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<p>Strathdee et al. (1992) mapped the FACC gene to chromosome 9q22.3 by in situ hybridization. </p><p>Gibson et al. (1994) used a polymorphism within the FACC gene to localize it within a 5-cM interval on 9q, bounded by D9S196/D9S197 and D9S176. Linkage analysis with 3 highly informative microsatellite polymorphisms flanking the FACC locus in 36 Fanconi anemia families showed that only 8% of them were linked to 9q22.3. The markers also allowed rapid exclusion of 56% of the families in the panel from complementation group C, thus substantially reducing the number of patients who need to be screened for FACC mutations. </p><p>By interspecific backcross analysis, Wevrick et al. (1993) showed that the cloned mouse homolog of Facc is located on mouse chromosome 13; the rat homolog is located on chromosome 17. A previously described anemic mouse mutant, 'flexed-tail,' had been mapped to the same region of chromosome 13. However, the authors found no evidence that Facc is mutated in flexed-tail mice. </p>
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<strong>Gene Function</strong>
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<p>Using a polyclonal antiserum against FACC and by immunofluorescence and subcellular fractionation studies of human cell lines, Youssoufian (1994) showed that the FACC protein was localized primarily to the cytoplasm under steady-state conditions, transient through the cell cycle, and exposure to crosslinking or cytotoxic agents. These observations suggested an indirect role for FACC in regulating DNA repair in group C Fanconi anemia. Yamashita et al. (1994) found that the wildtype FACC was a 60-kD protein, consistent with its predicted molecular mass. Different Fanconi anemia group C cell lines expressed full-length FACC, truncated FACC, or no detectable FACC polypeptide. In addition, the antiserum specifically immunoprecipitated a 50-kD and a 150-kD FACC-related protein (FRP-50 and FRP-150, respectively). Cell fractionation and immunofluorescence studies demonstrated that the FACC polypeptide localizes to the cytoplasm. </p><p>The pathogenesis of the bone marrow failure that is a consistent feature of Fanconi anemia was investigated by Segal et al. (1994), who pointed out that it is not known whether the pancytopenia is a direct and specific result of the inherited mutation or a consequence of accumulated stem cell losses resulting from the nonspecific DNA damage that is characteristic of the disease. They tested the hypothesis that the FACC protein plays a regulatory role in hematopoiesis by exposing normal human lymphocytes, bone marrow cells, endothelial cells, and fibroblasts to an antisense oligodeoxynucleotide (ODN) complementary to bases -4 to +14 of FACC mRNA. The mitomycin C assay demonstrated that the antisense ODN, but not missense or sense ODNs, repressed FACC gene expression in lymphocytes. The antisense ODN substantially reduced cytoplasmic levels of FACC mRNA in bone marrow cells and lymphocytes. Escalating doses of antisense ODN increasingly inhibited clonal growth of erythroid and granulocyte-macrophage progenitor cells but did not inhibit growth of fibroblasts or endothelial cells. Segal et al. (1994) concluded that while the FACC gene product plays a role in defining cellular tolerance to crosslinking agents, it also functions to regulate growth, differentiation, and/or survival of normal hematopoietic progenitor cells. </p><p>Although abnormalities in DNA repair had been suspected in Fanconi anemia complementation group C, localization of the FAC gene product to the cytoplasm had cast doubt on such a mechanism. Youssoufian (1996) monitored interstrand DNA crosslinking and found that the predominant defect in group C cells is in the initial induction of crosslinks, not in repair synthesis. The author demonstrated that both the crosslinking defect and the enhanced cytotoxicity of crosslinkers on Fanconi anemia group C cells were corrected completely by cytoplasmic isoforms of the FAC protein, but not by an isoform targeted to the nucleus. Furthermore, the major molecular defect in these cells preceded crosslink repair. Youssoufian (1996) also showed that the ability of FAC to impart resistance to FA-C cells reached a threshold despite overexpression of the gene product. Youssoufian (1996) proposed a cellular defense pathway for genotoxic agents in which FAC acts through a cytoplasmic compartment and at a proximal step within this pathway. </p><p>The tumor suppressor protein p53 (191170) can bind to specific target sequences and activate transcription of genes adjacent to these DNA elements. Liebetrau et al. (1997) noted that there are 2 p53 binding sites in the FACC gene, 1 in the promoter region and 1 in the coding region. Gel shift experiments showed that wildtype p53 protein binds to the p53 target sequence in the promoter region of the FACC gene. Transfection experiments showed that overexpression of wildtype p53 in human diploid fibroblasts and lymphoblasts augmented transcription of the FACC gene up to 3-fold. The transfection efficiency was approximately 15% for both cell types. The FACC expression activity for transformed cells was stimulated to an estimated level of 18- to 21-fold upon p53 overexpression. The tumor-derived p53 mutants, his175 and his273, that failed to bind DNA showed only a reduced stimulatory activity on FACC transcription. Liebetrau et al. (1997) concluded that the FACC gene can be added to the list of genes that interact with p53. </p><p>Cells derived from FA patients are sensitive to crosslinking agents and have a prolonged G2 phase, suggesting a cell cycle abnormality. Transfection of type-C FA cells with the FAC cDNA corrects these cellular abnormalities. Kupfer et al. (1997) found that in synchronized HeLa cells, FAC protein expression increased during S phase, was maximal at the G2/M transition, and declined during M phase. In addition, the FAC protein coimmunoprecipitated with the cyclin-dependent kinase, cdc2. A patient-derived mutant FAC polypeptide, containing a point mutation at L554P (613899.0001), failed to bind to cdc2. The FAC/cdc2 binding interaction therefore correlated with the functional activity of the FAC protein. Binding of FAC to cdc2 was mediated by the C-terminal 50 amino acids of FAC in a region of the protein required for FAC function. Taken together, these results suggested to Kupfer et al. (1997) that the binding of FAC and cdc2 is required for normal G2/M progression in mammalian cells. Absence of a functional interaction between FAC and cdc2 in FA cells may underlie the cell cycle abnormality and clinical abnormalities of FA. </p><p>Kupfer et al. (1997) demonstrated that FAA (607139) and FAC bind each other and form a complex. Protein binding correlated with the functional activity of FAA and FAC, as patient-derived mutant FAC, L554P (613899.0001), failed to bind FAA. Although unbound FAA and FAC localized predominantly to the cytoplasm, the FAA-FAC complex was found in similar abundance in both cytoplasm and nucleus. The results confirmed the interrelatedness of the FA genes in a pathway and suggested the cooperation of FAA and FAC in a nuclear function. </p><p>Garcia-Higuera et al. (1999) determined that FANCG (602956) is required for binding between FANCA and FANCC and that all 3 proteins are components of a nuclear protein complex. Analysis of the protein interactions formed by lymphoblasts from each of the complementation groups suggested that the interaction between FANCA and FANCG is constitutive and is not regulated by FANCC or by the products of other FA genes. In contrast, the binding of FANCC required FANCA/FANCG binding and the products of other FA genes. </p><p>Hoatlin et al. (1998) reproducibly detected approximately 10% of FAC protein in nuclear fractions. They concluded also that while the cytoplasmic localization of the FAC protein appears to be functionally important, the protein may also exert some essential nuclear function. </p><p>Activation of STAT1 (600555) in response to gamma-interferon (IFNG; 147570) is suppressed in hematopoietic cells from children with FA-C. However, interferon regulatory factor-1 (IRF1; 147575) is expressed at high levels in mutant FA-C cells (Parganas et al., 1998), suggesting that a non-STAT1 pathway is involved in constitutive activation of IRF1 in FA cells. In addition, hematopoietic cells from FA-C patients are hypersensitive to the apoptotic effects of IFNG. </p><p>Pang et al. (2000) reported that in IFNG-stimulated FA-C cells, phosphorylation of JAK1 (147795), JAK2 (147796), and IFNG receptor-alpha (IFNGR1; 107470) occurs normally, but STAT1 does not dock at the IFNGR1 chain, does not form nuclear DNA complexes, and does not induce the expression of IRF1. Expression of normal FANCC cDNA in mutant cells restored all of these normal functions of STAT1. Various cytokines stimulated the association of STAT1 with normal but not mutant (L554P) FANCC. Pang et al. (2000) proposed that hematopoietic defects in FA derive, at least in part, from an imbalance between mitogenic cues (due to reduced transduction of signals through growth factor receptors that activate STAT1) and mitogenic inhibitory cues (due to FANCC-dependent, STAT1-independent constitutive activation of mitotic inhibitory factors, such as IRF1). </p><p>Pang et al. (2001) presented evidence that a central, highly conserved domain of FANCC is required for functional interaction with STAT1 and that structural elements required for STAT1-related functions differ from those required for genotoxic responses to crosslinking agents. They commented that preservation of signaling capacity of cells bearing the 322delG mutation (613899.0007) may account for the reduced severity and later onset of bone marrow failure associated with this mutation. </p><p>Donahue and Campbell (2002) found that fibroblasts from FA patients from complementation groups A, C, D2 (613984), and G were hypersensitive to restriction enzyme-induced cell death following electroporation of restriction enzymes. These fibroblasts also showed reduced efficiency in plasmid end-joining activity. Normal sensitivity and activity were restored following retrovirus mediated expression of the respective FA cDNAs. Donahue and Campbell (2002) also found that the L554P FANCC allele has dominant-negative activity. A fibrosarcoma cell line overexpressing this mutation showed significantly diminished efficiency in rejoining cohesive-ended and blunt-ended linearized plasmids and were hypersensitive to restriction enzyme-induced cell death. </p><p>The Fanconi anemia nuclear complex (composed of the FA proteins A, C, G and F) is essential for protection against chromosome breakage. It activates the downstream protein FANCD2 by monoubiquitylation; this then forges an association with the BRCA1 (113705) protein at sites of DNA damage. Pace et al. (2002) showed that the FANCE (613976) protein is part of this nuclear complex, binding both FANCC and FANCD2. Indeed, FANCE is required for the nuclear accumulation of FANCC and provides a critical bridge between the FA complex and FANCD2. Disease-associated FANCC mutants do not bind to FANCE, cannot accumulate in the nucleus and are unable to prevent chromosome breakage. </p><p>Pichierri et al. (2002) studied the assembly and activation of the RMN (RAD50, 604040/MRE11, 600814/NBS1, 602667) complex by exposing cultured cells to the chemical interstrand crosslink inducers mitomycin C and photoactivated 8-methoxypsoralen. The authors determined that FA cells were unable to form subnuclear RMN foci in response to either interstrand crosslink inducer. In particular, mitomycin C-treated FANCC cells formed double-strand breaks and unhooked mitomycin C-induced interstrand crosslink similarly to FANCC wildtype cells. Additionally, the authors showed that the formation of foci, including BRCA1 (113705) and/or RAD51 (179617) proteins, was significantly delayed in FA cells. The authors concluded that FANCC may play a direct role in RMN focus assembly in response to interstrand crosslink inducers. </p><p>By coimmunoprecipitation of HeLa cell nuclear extracts, Meetei et al. (2003) identified 3 distinct multiprotein complexes associated with BLM (RECQL3; 604610). One of the complexes, designated BRAFT, contained the Fanconi anemia core complementation group proteins FANCA, FANCG, FANCC, FANCE, and FANCF (613897), as well as topoisomerase III-alpha (TOP3A; 601243) and replication protein A (RPA; see 179835). BLM complexes isolated from an FA cell line had a lower molecular mass, likely due to loss of FANCA and other FA components. BLM- and FANCA-associated complexes had DNA unwinding activity, and BLM was required for this activity. </p><p>Zhang et al. (2004) used immunoprecipitation and reconstituted kinase assays to show that the FANCC, FANCA, and FANCG proteins functionally interacted with and inhibited the proapoptotic kinase PKR (176871), a kinase that represses translation when activated. PKR showed strongest binding to the FANCC protein. PKR activity was increased in bone marrow cells of patients with Fanconi anemia with mutations in the FANCC, FANCA, and FANCG genes. All 3 of these cell lines showed significant increases in PKR bound to the FANCC protein, which correlated with increased PKR activation. The cells also showed hypersensitivity to growth repression mediated by IFN-gamma and TNF-alpha (191160). Forced expression of a patient-derived FANCC mutation increased PKR activation and cell death. Zhang et al. (2004) concluded that FA mutations cause increased binding of PKR to FANCC and increased PKR activation, leading to growth inhibition of hematopoietic progenitors and bone marrow failure in Fanconi anemia. </p><p>Pace et al. (2010) found a genetic interaction between the FANCC gene and the nonhomologous end joining (NHEJ) factor Ku70 (152690). Disruption of both FANCC and Ku70 suppressed sensitivity to crosslinking agents, diminished chromosome breaks, and reversed defective homologous recombination. Ku70 binds directly to free DNA ends, committing them to NHEJ repair. Pace et al. (2010) showed that purified FANCD2, a downstream effector of the Fanconi anemia pathway, might antagonize Ku70 activity by modifying such DNA substrates. Pace et al. (2010) concluded that these results reveal a function for the Fanconi anemia pathway in processing DNA ends, thereby diverting double-strand break repair from abortive NHEJ and toward homologous recombination. </p>
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<p>Chen et al. (1996) found that mice homozygous for a disrupted Fac gene did not show developmental abnormalities or hematologic defects during observations up to 9 months of age. However, their spleen cells had dramatically increased numbers of chromosomal aberrations in response to mitomycin C (MMC) and diepoxybutane. Homozygous male and female mice also had compromised gametogenesis, leading to markedly impaired fertility, a characteristic of Fanconi anemia patients. </p><p>Whitney et al. (1996) generated mice homozygous for a targeted deletion of exon 9 of the murine FA complementation group C gene. They selected this exon for knockout since there was evidence from mutation analysis in patients with FAC that the carboxy terminus of the protein is essential for its function. Mutant mice had normal neonatal viability and gross morphology. Their cells demonstrated chromosome breakage and crosslinker sensitivity. Male and female mutant mice had reduced numbers of germ cells and females had markedly impaired fertility. No anemia was detectable during the first year of life. The colony-forming capacity of bone marrow progenitor cells was abnormal and these cells were hypersensitive to gamma-interferon (147570). Whitney et al. (1996) concluded that this abnormal sensitivity to gamma-interferon may form the basis for bone marrow failure in Fanconi anemia. </p><p>Pulliam-Leath et al. (2010) found that Fancc -/-;Fancg -/- (602956) double-mutant mice developed spontaneous hematologic sequelae, including bone marrow failure, acute myeloid leukemia, myelodysplasia, and complex random chromosomal abnormalities, that Fancc -/- mice or Fancg -/- mice did not develop. Studies on cells derived from single-mutant mice showed that loss of Fancg resulted in a more severe defect in multiple hematopoietic compartments than loss of Fancc, suggesting that the 2 genes have nonoverlapping roles in hematopoiesis. However, both single- and double-mutant cells showed similar sensitivity to a DNA crosslinking agent. The phenotype of the double-mutant mice was most consistent with that of human patients with Fanconi anemia. </p><p>Rhee et al. (2010) studied the role of Fancc in telomere length regulation in mice. Deletion of Fancc did not affect telomerase activity, telomere length, or telomeric end-capping in a mouse strain possessing intrinsically long telomeres. However, ablation of Fancc did exacerbate telomere attrition when murine bone marrow cells experienced high cell turnover after serial transplantation. When Fancc-null mice were crossed into a telomerase reverse transcriptase (TERT; 187270) heterozygous or null background (Tert +/- or Tert -/-) with short telomeres, Fancc deficiency led to an increase in the incidence of telomere sister chromatid exchange. In contrast, these phenotypes were not observed in Tert mutant mice with long telomeres. The authors concluded that Fancc deficiency accelerates telomere shortening during high turnover of hematopoietic cells and may promote telomere recombination initiated by short telomeres. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>10 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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<h4>
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<span class="mim-font">
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<strong>.0001 FANCONI ANEMIA, COMPLEMENTATION GROUP C</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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FANCC, LEU554PRO
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<br />
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SNP: rs104886458,
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gnomAD: rs104886458,
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ClinVar: RCV000012823, RCV000058925, RCV001221431, RCV002399319, RCV003421917
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</span>
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</div>
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<span class="mim-text-font">
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<p>Strathdee et al. (1992) and Gavish et al. (1992) demonstrated that HSC536N cells, which represented the only confirmed Fanconi anemia cell line of complementation group C (FANCC; 227645), have a T-to-C transition at base 1913 that changes codon 553 from leucine to proline (L553P). Gavish et al. (1993) corrected the previously published FACC cDNA sequence which omitted 3 nucleotides. The corrected sequence predicts a 1,677-bp ORF and a protein of 558 amino acids. Therefore, the previously reported L553P mutation is, in fact, L554P. To avoid confusion, they chose to refer to the site of the mutation as base 1661, on the basis of the ORF, and amino acid 554 on the basis of its location in the protein. Using site-directed in vitro mutagenesis, Gavish et al. (1993) demonstrated that the leu554-to-pro mutation completely abolishes the activity of the FACC protein as analyzed by functional complementation assay. </p><p>The polypeptide encoded by the FAC gene binds to a group of cytoplasmic proteins in vitro and may form a multimeric complex. The leu554-to-pro mutant allele fails to correct the sensitivity of FA group C cells to mitomycin C. Youssoufian et al. (1996) reasoned that overexpression of the mutant protein in a wildtype cellular background might induce the FA phenotype by competing with endogenous FAC for binding to the accessory proteins. After stable transfection of human kidney 293 cells with wildtype and a mutant FAC allele containing the L554P substitution, 4 independent clones that expressed 4- to 15-fold higher levels of transcript from the mutant transgene relative to the endogenous FAC gene showed hypersensitivity to mitomycin C. By contrast, both parental and FAC-overexpressing cells maintained their relative resistance to mitomycin C. No differences in the biosynthesis, subcellular localization, and protein interactions of the normal and mutant proteins were detected. Youssoufian et al. (1996) stated that the induction of the FA phenotype in this system is compatible with the competition hypothesis and provides support for a functional role of the FAC-binding proteins in vivo. </p>
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 FANCONI ANEMIA, COMPLEMENTATION GROUP C</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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FANCC, ARG185TER
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<br />
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SNP: rs121917783,
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gnomAD: rs121917783,
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ClinVar: RCV000012824, RCV000115356, RCV000471314, RCV000568180, RCV001356657, RCV004748517
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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>Using the BbvI restriction site change as a screening method, Gibson et al. (1992) found no instance of the L554P FANCC mutation (613899.0001) in 38 unrelated patients with Fanconi anemia (FANCC; 227645). However, they identified a truncated transcript that was shown to be due to a nonsense mutation changing arginine-185 to a stop codon (R185X). The mutation was a C-to-T transition at nucleotide 808.</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 FANCONI ANEMIA, COMPLEMENTATION GROUP C</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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FANCC, IVS4, A-T, +4
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<br />
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SNP: rs104886456,
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gnomAD: rs104886456,
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ClinVar: RCV000012825, RCV000115354, RCV000197192, RCV000562912, RCV001358012, RCV004748518
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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>Using reverse transcription PCR and chemical mismatch cleavage (CMC), Whitney et al. (1993) demonstrated homozygosity for an identical splice mutation in the FANCC gene in 2 Ashkenazi Jewish patients with Fanconi anemia (FANCC; 227645). Three additional patients bearing this allele were found through screening 21 other families. A single base change in the fourth intronic base changed the sequence from a consensus A to T, resulting in deletion of the 111-bp exon 4. They referred to the allele as IVS4+4, A-to-T. </p><p>Whitney et al. (1994) used allele-specific oligonucleotide hybridization to determine the frequency of this mutation in Ashkenazi Jews with Fanconi anemia (FA). They studied 11 patients, each of whom had 2 Jewish parents, and 1 patient who had a Jewish mother and a non-Jewish father. The mutation was found in 19 of the 23 Jewish FA chromosomes (83%), but was not found in 2 other Jewish patients, in 39 non-Jewish patients, or in 130 non-Jewish persons without FA. Two of 315 Jewish individuals without FA were found to be carriers of the mutation. Verlander et al. (1995) developed amplification refractory mutation system (ARMS) assays for 5 known mutations in FAC and used these assays to determine the carrier frequency of the IVS4 +4 A-to-T mutation in an Ashkenazi Jewish population. Among 3,104 Jewish individuals, primarily of Ashkenazi descent, 35 IVS4 carriers were identified, for a carrier frequency of 1 in 89 (1.1%). Among 563 Iraqi Jews, no carriers of the IVS4 mutation were found. They suggested that a founder effect is responsible for the high frequency of the mutation in Ashkenazim and that the carrier frequency of more than 1% justified inclusion of this mutation in the battery of tests routinely provided to the Jewish population. </p><p>Verlinsky et al. (2001) presented a means for guaranteeing HLA-matching tissues for stem cell transplantation. The advent of single-cell PCR provided the opportunity for combined preimplantation genetic diagnosis (PGD) and HLA antigen testing. They identified a couple, both carriers of the IVS4+4A-T mutation in the FANCC gene, with an affected child requiring an HLA-compatible donor for cord blood transplantation. They used DNA analysis of single blastomeres to preselect unaffected embryos representing an HLA match for the affected sib. The transfer of mutation-negative, HLA-compatible embryos resulted in the pregnancy and birth of an unaffected child. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0004 FANCONI ANEMIA, COMPLEMENTATION GROUP C</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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FANCC, GLN13TER
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<br />
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SNP: rs121917784,
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gnomAD: rs121917784,
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ClinVar: RCV000012826, RCV000115351, RCV000476519, RCV001021181, RCV004748519
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
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<p>By mismatch analysis with chemical cleavage with osmium tetroxide and hydroxylamine, Murer-Orlando et al. (1993) demonstrated compound heterozygosity for a gln13-to-ter (Q13X) mutation in exon 1 of the FACC gene and an R548X mutation in exon 14 (613899.0005) in chorionic villus samples obtained for prenatal diagnosis of Fanconi anemia of complementation group C (FANCC; 227645). The 2 mutations were derived from the father and mother, respectively, and were also demonstrated in an affected sib. Chromosome breakage analysis on cultured chorionic cells had shown a higher response to diepoxybutane in the pregnancy at risk than in normal control samples. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0005 FANCONI ANEMIA, COMPLEMENTATION GROUP C</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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FANCC, ARG548TER
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<br />
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SNP: rs104886457,
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gnomAD: rs104886457,
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ClinVar: RCV000012827, RCV000058924, RCV000205197, RCV000572840
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>For discussion of the arg548-to-ter (R548X) mutation in the FANCC gene that was found in compound heterozygous state in chorionic villus samples obtained for prenatal diagnosis of Fanconi anemia of complementation group C (FANCC; 227645) by Murer-Orlando et al. (1993), see 613899.0004. </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>
|
|
<span class="mim-font">
|
|
<strong>.0006 FANCONI ANEMIA, COMPLEMENTATION GROUP C</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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FANCC, 1-BP INS, 1806A
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<br />
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SNP: rs794726667,
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gnomAD: rs794726667,
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ClinVar: RCV000012828, RCV001851810, RCV004619189, RCV004777561
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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>Lo Ten Foe et al. (1996) described a frameshift mutation in the FANCC gene resulting from insertion of an adenine after nucleotide 1806 in exon 14. The insertion caused a frameshift that was expected to give rise to a truncated protein of 526 amino acids, which is shorter than the protein resulting from premature termination caused by the R548X mutation (613899.0005), and therefore presumed to be inactive. Mutations in exon 14 are the most C-terminal of 7 pathogenic mutations that the authors discussed. Three pathogenic mutations are located in exon 14, suggesting that the C-terminal part of FAC protein is essential for an as yet unknown function. The other 2 exon 14 mutations reported to that time were L554P (613899.0001) and R548X (613899.0005). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0007 FANCONI ANEMIA, COMPLEMENTATION GROUP C</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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FANCC, 1-BP DEL, 322G
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<br />
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SNP: rs104886459,
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gnomAD: rs104886459,
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ClinVar: RCV000012829, RCV000058926, RCV000460906, RCV001025667, RCV004748520
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>Mutations within the Fanconi anemia complementation group C (FAC) gene account for approximately 14% of diagnosed Fanconi anemia (FA; see 227645) cases. Two mutations, one in exon 1 (322delG) and the other in exon 4 (IVS4+4A-T; 613899.0003), account for 90% of known FAC mutations. The 322delG mutation results in a mild FA phenotype, while the IVS4 donor splice site mutation results in a severe FA phenotype. To determine the molecular basis for this clinical variability, Yamashita et al. (1996) analyzed patient-derived cell lines for the expression of characteristic mutant FAC polypeptides. All cell lines with the 322delG mutation expressed a 50-kD FAC polypeptide, shown to be an N-terminal truncated isoform of FAC reinitiated at methionine 55. All cell lines with the IVS4 donor splice site mutation lacked FRP-50 (FAC-related protein). Overexpression of a cDNA encoding FRP-50 in a FAC cell line resulted in partial correction of mitomycin C sensitivity. Thus, expression of an N-terminal truncated FAC protein accounted, at least in part, for the clinical heterogeneity. </p><p>Pang et al. (2001) observed that cells bearing the 322delG mutation, which preserves a conserved region of FANCC, showed normal STAT1 activation but remained hypersensitive to mitomycin C. Preservation of signaling capacity of cells bearing this mutation may account for the reduced severity and later onset of bone marrow failure associated with it. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0008 FANCONI ANEMIA, COMPLEMENTATION GROUP C</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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FANCC, LEU496ARG
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<br />
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SNP: rs121917785,
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ClinVar: RCV000012830
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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 Fanconi anemia of complementation group C (FANCC; 227645) and his affected brother, Waisfisz et al. (1999) detected a homozygous 1749T-to-G missense mutation in the FANCC gene, predicting a change from leucine to arginine at codon 496 (L496R). Cytogenetic analysis revealed the patient and his brother to be mosaics with an additional de novo 1748C-to-T transition at 1 allele. The combination of the 2 mutations on 1 allele predicted a change from the mutant arginine to cysteine. Evaluation of the functional status of the proteins encoded by both alleles showed full correction by the cDNA with both mutations. </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>.0009 FANCONI ANEMIA, COMPLEMENTATION GROUP C</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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FANCC, IVS2DS, G-T, +1
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<br />
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SNP: rs794726668,
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ClinVar: RCV000012831, RCV001221363, RCV001588811
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In affected members of 2 unrelated but consanguineous families of Arabian ancestry with Fanconi anemia of complementation group C (FANCC; 227645), Hartmann et al. (2010) identified a homozygous G-to-T transversion in intron 2 of the FANCC gene (165+1G-T), changing a highly conserved GT dinucleotide to TT at the 5-prime splice site. Two affected individuals from a family of mixed Arabian/British ancestry were compound heterozygous for the intron 2 mutation and a 250-bp deletion (613899.0010), resulting in the skipping of exons 2 and 3. The phenotype was relatively mild in the 2 Arabian families, but was severe in the 2 patients in the mixed Arabian/British family, who died at ages 13.5 and 16 years. RT-PCR analysis of the splice site mutation yielded 4 distinct products, including the wildtype product at 27% of the total transcripts. Functional analysis of the splice site mutation within splicing reporters showed that increasing complementarity to U1 snRNA could reconstitute splicing at the noncanonical TT dinucleotide, and that artificial TT-adapted U1 snRNA improved correct mRNA processing at the mutant TT splice site. These results were replicated in patient fibroblasts, with correctly spliced transcripts increasing from about 30% to 56-58%. Finally, Hartmann et al. (2010) demonstrated that use of lentiviral vectors as a delivery system to introduce expression cassettes for TT-adapted U1 snRNAs into primary FANCC patient fibroblasts allowed the continuous correction of the DNA damage-induced G2 cell-cycle arrest in these cells. These findings indicated an alternative transcript-targeting approach for genetic therapy of inherited splice site mutations. </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>.0010 FANCONI ANEMIA, COMPLEMENTATION GROUP C</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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FANCC, 250-BP DEL
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<br />
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ClinVar: RCV000012832
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
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<p>For discussion of the 250-bp deletion in the FANCC gene that was found in compound heterozygous state in patients with Fanconi anemia of complementation group C (FANCC; 227645) by Hartmann et al. (2010), see 613899.0009. </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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chen, M., Tomkins, D. J., Auerbach, W., McKerlie, C., Youssoufian, H., Liu, L., Gan, O., Carreau, M., Auerbach, A., Groves, T., Guidos, C. J., Freedman, M. H., Cross, J., Percy, D. H., Dick, J. E., Joyner, A. L., Buchwald, M.
|
|
<strong>Inactivation of Fac in mice produces inducible chromosomal instability and reduced fertility reminiscent of Fanconi anaemia.</strong>
|
|
Nature Genet. 12: 448-451, 1996.
|
|
|
|
|
|
[PubMed: 8630504]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0496-448]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Donahue, S. L., Campbell, C.
|
|
<strong>A DNA double strand break repair defect in Fanconi anemia fibroblasts.</strong>
|
|
J. Biol. Chem. 277: 46243-46247, 2002.
|
|
|
|
|
|
[PubMed: 12361951]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M207937200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Garcia-Higuera, I., Kuang, Y., Naf, D., Wasik, J., D'Andrea, A. D.
|
|
<strong>Fanconi anemia proteins FANCA, FANCC, and FANCG/XRCC9 interact in a functional nuclear complex.</strong>
|
|
Molec. Cell. Biol. 19: 4866-4873, 1999.
|
|
|
|
|
|
[PubMed: 10373536]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1128/MCB.19.7.4866]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gavish, H., dos Santos, C. C., Buchwald, M.
|
|
<strong>Generation of a non-functional Fanconi anemia group C protein (FACC) by site-directed in vitro mutagenesis. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 51 (suppl.): A128 only, 1992.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gavish, H., dos Santos, C. C., Buchwald, M.
|
|
<strong>A leu554-to-pro substitution completely abolishes the functional complementing activity of the Fanconi anemia (FACC) protein.</strong>
|
|
Hum. Molec. Genet. 2: 123-126, 1993.
|
|
|
|
|
|
[PubMed: 8499901]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/2.2.123]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gibson, R. A., Buchwald, M., Roberts, R. G., Mathew, C. G.
|
|
<strong>Characterisation of the exon structure of the Fanconi anaemia group C gene by vectorette PCR.</strong>
|
|
Hum. Molec. Genet. 2: 35-38, 1993.
|
|
|
|
|
|
[PubMed: 8490620]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/2.1.35]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gibson, R. A., Ford, D., Jansen, S., Savoia, A., Havenga, C., Milner, R. D., de Ravel, T. J., Cohn, R. J., Ball, S. E., Roberts, I., Llerena, J. C., Vorechovsky, I., Pearson, T., Birjandi, F., Hussein, S. S., Murer-Orlando, M., Easton, D. F., Mathew, C. G.
|
|
<strong>Genetic mapping of the FACC gene and linkage analysis in Fanconi anaemia families.</strong>
|
|
J. Med. Genet. 31: 868-871, 1994.
|
|
|
|
|
|
[PubMed: 7853372]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.31.11.868]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gibson, R. A., Hajianpour, A., Buchwald, M., Mathew, C. G.
|
|
<strong>Screening the FACC gene for mutations in patients with Fanconi anaemia. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 51 (suppl.): A216 only, 1992.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hartmann, L., Neveling, K., Borkens, S., Schneider, H., Freund, M., Grassman, E., Theiss, S., Wawer, A., Burdach, S., Auerbach, A. D., Schindler, D., Hanenberg, H., Schaal, H.
|
|
<strong>Correct mRNA processing at a mutant TT splice donor in FANCC ameliorates the clinical phenotype in patients and is enhanced by delivery of suppressor U1 snRNAs.</strong>
|
|
Am. J. Hum. Genet. 87: 480-493, 2010.
|
|
|
|
|
|
[PubMed: 20869034]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ajhg.2010.08.016]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hoatlin, M. E., Christianson, T. A., Keeble, W. W., Hammond, A. T., Zhi, Y., Heinrich, M. C., Tower, P. A., Bagby, G. C., Jr.
|
|
<strong>The Fanconi anemia group C gene product is located in both the nucleus and cytoplasm of human cells.</strong>
|
|
Blood 91: 1418-1425, 1998.
|
|
|
|
|
|
[PubMed: 9454773]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kupfer, G. M., Naf, D., Suliman, A., Pulsipher, M., D'Andrea, A. D.
|
|
<strong>The Fanconi anaemia proteins, FAA and FAC, interact to form a nuclear complex.</strong>
|
|
Nature Genet. 17: 487-490, 1997.
|
|
|
|
|
|
[PubMed: 9398857]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1297-487]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kupfer, G. M., Yamashita, T., Naf, D., Suliman, A., Asano, S., D'Andrea, A. D.
|
|
<strong>The Fanconi anemia polypeptide, FAC, binds to the cyclin-dependent kinase, cdc2.</strong>
|
|
Blood 90: 1047-1054, 1997.
|
|
|
|
|
|
[PubMed: 9242535]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Liebetrau, W., Budde, A., Savoia, A., Grummt, F., Hoehn, H.
|
|
<strong>p53 activates Fanconi anemia group C gene expression.</strong>
|
|
Hum. Molec. Genet. 6: 277-283, 1997.
|
|
|
|
|
|
[PubMed: 9063748]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/6.2.277]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lo Ten Foe, J. R., Rooimans, M. A., Joenje, H., Arwert, F.
|
|
<strong>Novel frameshift mutation (1806insA) in exon 14 of the Fanconi anemia C gene, FAC.</strong>
|
|
Hum. Mutat. 7: 264-265, 1996.
|
|
|
|
|
|
[PubMed: 8829660]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1996)7:3<264::AID-HUMU11>3.0.CO;2-0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Meetei, A. R., Sechi, S., Wallisch, M., Yang, D., Young, M. K., Joenje, H., Hoatlin, M. E., Wang, W.
|
|
<strong>A multiprotein nuclear complex connects Fanconi anemia and Bloom syndrome.</strong>
|
|
Molec. Cell. Biol. 23: 3417-3426, 2003.
|
|
|
|
|
|
[PubMed: 12724401]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1128/MCB.23.10.3417-3426.2003]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Murer-Orlando, M., Llerena, J. C., Jr., Birjandi, F., Gibson, R. A., Mathew, C. G.
|
|
<strong>FACC gene mutations and early prenatal diagnosis of Fanconi's anaemia. (Letter)</strong>
|
|
Lancet 342: 686 only, 1993.
|
|
|
|
|
|
[PubMed: 8103176]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0140-6736(93)91800-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pace, P., Johnson, M., Tan, W. M., Mosedale, G., Sng, C., Hoatlin, M., de Winter, J., Joenje, H., Gergely, F., Patel, K. J.
|
|
<strong>FANCE: the link between Fanconi anaemia complex assembly and activity.</strong>
|
|
EMBO J. 21: 3414-3423, 2002.
|
|
|
|
|
|
[PubMed: 12093742]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/emboj/cdf355]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pace, P., Mosedale, G., Hodskinson, M. R., Rosado, I. V. Sivasubramaniam, M., Patel, K. J.
|
|
<strong>Ku70 corrupts DNA repair in the absence of the Fanconi anemia pathway.</strong>
|
|
Science 329: 219-223, 2010.
|
|
|
|
|
|
[PubMed: 20538911]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1192277]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pang, Q., Christianson, T. A., Keeble, W., Diaz, J., Faulkner, G. R., Reifsteck, C., Olson, S., Bagby, G. C.
|
|
<strong>The Fanconi anemia complementation group C gene product: structural evidence of multifunctionality.</strong>
|
|
Blood 98: 1392-1401, 2001.
|
|
|
|
|
|
[PubMed: 11520787]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood.v98.5.1392]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pang, Q., Fagerlie, S., Christianson, T. A., Keeble, W., Faulkner, G., Diaz, J., Rathbun, R. K., Bagby, G. C.
|
|
<strong>The Fanconi anemia protein FANCC binds to and facilitates the activation of STAT1 by gamma interferon and hematopoietic growth factors.</strong>
|
|
Molec. Cell. Biol. 20: 4724-4735, 2000.
|
|
|
|
|
|
[PubMed: 10848598]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1128/MCB.20.13.4724-4735.2000]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Parganas, E., Wang, D., Stravopodis, D., Topham, D. J., Marine, J.-C., Teglund, S., Vanin, E. F., Bodner, S., Colamonici, O. R., van Deursen, J. M., Grosveld, G., Ihle, J. N.
|
|
<strong>Jak2 is essential for signaling through a variety of cytokine receptors.</strong>
|
|
Cell 93: 385-395, 1998.
|
|
|
|
|
|
[PubMed: 9590173]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0092-8674(00)81167-8]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pichierri, P., Averbeck, D., Rosselli, F.
|
|
<strong>DNA cross-link-dependent RAD50/MRE11/NBS1 subnuclear assembly requires the Fanconi anemia C protein.</strong>
|
|
Hum. Molec. Genet. 11: 2531-2546, 2002. Note: Erratum: Hum. Molec. Genet. 13: 1289 only, 2004.
|
|
|
|
|
|
[PubMed: 12354779]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/11.21.2531]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pulliam-Leath, A. C., Ciccone, S. L., Nalepa, G., Li, X., Si, Y., Miravalle, L., Smith, D., Yuan, J., Li, J., Anur, P., Orazi, A., Vance, G. H., Yang, F.-C., Hanenberg, H., Bagby, G. C., Clapp, D. W.
|
|
<strong>Genetic disruption of both Fancc and Fancg in mice recapitulates the hematopoietic manifestations of Fanconi anemia.</strong>
|
|
Blood 116: 2915-2920, 2010.
|
|
|
|
|
|
[PubMed: 20606166]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2009-08-240747]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rhee, D. B., Wang, Y., Mizesko, M., Zhou, F., Haneline, L., Liu, Y.
|
|
<strong>FANCC suppresses short telomere-initiated telomere sister chromatid exchange.</strong>
|
|
Hum. Molec. Genet. 19: 879-887, 2010.
|
|
|
|
|
|
[PubMed: 20022886]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddp556]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Riley, J., Butler, R., Ogilvie, D., Finniear, R., Jenner, D., Powell, S., Anand, R., Smith, J. C., Markham, A. F.
|
|
<strong>A novel, rapid method for the isolation of terminal sequences from yeast artificial chromosome (YAC) clones.</strong>
|
|
Nucleic Acids Res. 18: 2887-2890, 1990.
|
|
|
|
|
|
[PubMed: 2161516]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/nar/18.10.2887]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Roberts, R. G., Coffey, A. J., Bobrow, M., Bentley, D. R.
|
|
<strong>Determination of the exon structure of the distal portion of the dystrophin gene by vectorette PCR.</strong>
|
|
Genomics 13: 942-950, 1992.
|
|
|
|
|
|
[PubMed: 1505985]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(92)90005-d]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Savoia, A., Centra, M., Ianzano, L., de Cillis, G. P., Zelante, L., Buchwald, M.
|
|
<strong>Characterization of the 5-prime region of the Fanconi anaemia group C (FACC) gene.</strong>
|
|
Hum. Molec. Genet. 4: 1321-1326, 1995.
|
|
|
|
|
|
[PubMed: 7581369]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/4.8.1321]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Segal, G. M., Magenis, R. E., Brown, M., Keeble, W., Smith, T. D., Heinrich, M. C., Bagby, G. C., Jr.
|
|
<strong>Repression of Fanconi anemia gene (FACC) expression inhibits growth of hematopoietic progenitor cells.</strong>
|
|
J. Clin. Invest. 94: 846-852, 1994.
|
|
|
|
|
|
[PubMed: 7518843]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI117405]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Strathdee, C. A., Duncan, A. M. V., Buchwald, M.
|
|
<strong>Evidence for at least four Fanconi anaemia genes including FACC on chromosome 9.</strong>
|
|
Nature Genet. 1: 196-198, 1992.
|
|
|
|
|
|
[PubMed: 1303234]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0692-196]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Strathdee, C. A., Gavish, H., Shannon, W. R., Buchwald, M.
|
|
<strong>Cloning of cDNAs for Fanconi's anaemia by functional complementation.</strong>
|
|
Nature 356: 763-767, 1992. Note: Erratum: Nature 358: 434 only, 1992.
|
|
|
|
|
|
[PubMed: 1574115]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/356763a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Verlander, P. C., Kaporis, A., Liu, Q., Zhang, Q., Seligsohn, U., Auerbach, A. D.
|
|
<strong>Carrier frequency of the IVS4 + 4 A-to-T mutation of the Fanconi anemia gene FAC in the Ashkenazi Jewish population.</strong>
|
|
Blood 86: 4034-4038, 1995.
|
|
|
|
|
|
[PubMed: 7492758]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Verlinsky, Y., Rechitsky, S., Schoolcraft, W., Strom, C., Kuliev, A.
|
|
<strong>Preimplantation diagnosis for Fanconi anemia combined with HLA matching.</strong>
|
|
JAMA 285: 3130-3133, 2001.
|
|
|
|
|
|
[PubMed: 11427142]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/jama.285.24.3130]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Waisfisz, Q., Morgan, N. V., Savino, M., de Winter, J. P., van Berkel, C. G. M., Hoatlin, M. E., Ianzano, L., Gibson, R. A., Arwert, F., Savoia, A., Mathew, C. G., Pronk, J. C., Joenje, H.
|
|
<strong>Spontaneous functional correction of homozygous Fanconi anaemia alleles reveals novel mechanistic basis for reverse mosaicism.</strong>
|
|
Nature Genet. 22: 379-383, 1999.
|
|
|
|
|
|
[PubMed: 10431244]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/11956]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wevrick, R., Barker, J. E., Eppig, J. T., Nadeau, J. H., Buchwald, M.
|
|
<strong>Expression of the Fanconi anemia group C gene in the mouse. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 51 (suppl.): A137 only, 1992.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wevrick, R., Barker, J. E., Nadeau, J. H., Szpirer, C., Buchwald, M.
|
|
<strong>Mapping of the murine and rat Facc genes and assessment of flexed-tail as a candidate mouse homolog of Fanconi anemia group C.</strong>
|
|
Mammalian Genome 4: 440-444, 1993.
|
|
|
|
|
|
[PubMed: 7690622]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00296818]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Whitney, M. A., Jakobs, P., Kaback, M., Moses, R. E., Grompe, M.
|
|
<strong>The Ashkenazi Jewish Fanconi anemia mutation: incidence among patients and carrier frequency in the at-risk population.</strong>
|
|
Hum. Mutat. 3: 339-341, 1994.
|
|
|
|
|
|
[PubMed: 8081385]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.1380030402]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Whitney, M. A., Royle, G., Low, M. J., Kelly, M. A., Axthelm, M. K., Reifsteck, C., Olson, S., Braun, R. E., Heinrich, M. C., Rathbun, R. K., Bagby, G. C., Grompe, M.
|
|
<strong>Germ cell defects and hematopoietic hypersensitivity to gamma-interferon in mice with a targeted disruption of the Fanconi anemia C gene.</strong>
|
|
Blood 88: 49-58, 1996.
|
|
|
|
|
|
[PubMed: 8704201]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Whitney, M. A., Saito, H., Jakobs, P. M., Gibson, R. A., Moses, R. E., Grompe, M.
|
|
<strong>A common mutation in the FACC gene causes Fanconi anaemia in Ashkenazi Jews.</strong>
|
|
Nature Genet. 4: 202-205, 1993.
|
|
|
|
|
|
[PubMed: 8348157]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0693-202]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yamashita, T., Barber, D. L., Zhu, Y., Wu, N., D'Andrea, A. D.
|
|
<strong>The Fanconi anemia polypeptide FACC is localized to the cytoplasm.</strong>
|
|
Proc. Nat. Acad. Sci. 91: 6712-6716, 1994.
|
|
|
|
|
|
[PubMed: 7517562]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.91.14.6712]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yamashita, T., Wu, N., Kupfer, G., Corless, C., Joenje, H., Grompe, M., D'Andrea, A. D.
|
|
<strong>Clinical variability of Fanconi anemia (type C) results from expression of an amino terminal truncated Fanconi anemia complementation group C polypeptide with partial activity.</strong>
|
|
Blood 87: 4424-4432, 1996.
|
|
|
|
|
|
[PubMed: 8639804]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Youssoufian, H., Li, Y., Martin, M. E., Buchwald, M.
|
|
<strong>Induction of Fanconi anemia cellular phenotype in human 293 cells by overexpression of a mutant FAC allele.</strong>
|
|
J. Clin. Invest. 97: 957-962, 1996.
|
|
|
|
|
|
[PubMed: 8613549]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI118519]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Youssoufian, H.
|
|
<strong>Localization of Fanconi anemia C protein to the cytoplasm of mammalian cells.</strong>
|
|
Proc. Nat. Acad. Sci. 91: 7975-7979, 1994.
|
|
|
|
|
|
[PubMed: 8058745]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.91.17.7975]
|
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|
|
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</p>
|
|
</li>
|
|
|
|
<li>
|
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<p class="mim-text-font">
|
|
Youssoufian, H.
|
|
<strong>Cytoplasmic localization of FAC is essential for the correction of a prerepair defect in Fanconi anemia group C cells.</strong>
|
|
J. Clin. Invest. 97: 2003-2010, 1996.
|
|
|
|
|
|
[PubMed: 8621788]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI118635]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Zhang, X., Li, J., Sejas, D. P., Rathbun, K. R., Bagby, G. C., Pang, Q.
|
|
<strong>The Fanconi anemia proteins functionally interact with the protein kinase regulated by RNA (PKR).</strong>
|
|
J. Biol. Chem. 279: 43910-43919, 2004.
|
|
|
|
|
|
[PubMed: 15299030]
|
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[Full Text: https://doi.org/10.1074/jbc.M403884200]
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