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Entry
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- *602656 - ENDONUCLEASE III-LIKE 1; NTHL1
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- OMIM
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<p>
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<span class="h4">*602656</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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<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="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/602656">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 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-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=ENSG00000065057;t=ENST00000651570" 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=4913" 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=602656" 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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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000065057;t=ENST00000651570" 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_001318193,NM_001318194,NM_002528,XM_047434171" 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_002528" 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=602656" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=04039&isoform_id=04039_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
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<div><a href="https://www.proteinatlas.org/search/NTHL1" 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/1753174,1772974,1800271,1881376,3522921,3550834,12804311,20136744,38197140,119605968,311350018,311350020,311350022,311350024,311350026,311350028,311350030,311350032,311350034,311350036,311350038,311350040,311350042,311350044,311350046,311350048,311350050,311350052,311350054,311350056,311350058,311350060,311350062,311350064,311350066,311350068,311350070,311350072,311350074,311350076,311350078,311350080,311350082,311350084,311350086,311350088,311350090,311350092,311350094,311350096,970598256,1514769207,1514769209,2217306122,2462549176,2789064980,2789065049,2789065129,2789065204,2813266245" 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/P78549" 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=4913" 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=ENSG00000065057;t=ENST00000651570" 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=NTHL1" 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=NTHL1" 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+4913" 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/NTHL1" 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:4913" 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/4913" 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=chr16&hgg_gene=ENST00000651570.2&hgg_start=2039820&hgg_end=2047834&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:8028" 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:8028" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=602656[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=602656[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000065057" 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=NTHL1" 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=NTHL1" 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=NTHL1" 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=NTHL1&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/PA31811" 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:8028" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0032907.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1313275" 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/NTHL1#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:1313275" 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/4913/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=4913" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00011201;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-120511-4" 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="mimCellLines">
|
|
<span class="panel-title">
|
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<span class="small">
|
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" 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="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</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="mimCellLinesLinksFold" 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://catalog.coriell.org/Search?q=OmimNum:602656" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
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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:4913" 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=NTHL1&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
|
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</div>
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<div>
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<span class="h3">
|
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<span class="mim-font mim-tip-hint" title="Gene description">
|
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<span class="text-danger"><strong>*</strong></span>
|
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602656
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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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|
ENDONUCLEASE III-LIKE 1; NTHL1
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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>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
ENDONUCLEASE III, E. COLI, HOMOLOG OF; NTH1<br />
|
|
OCTS3
|
|
</span>
|
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</h4>
|
|
</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>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=NTHL1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">NTHL1</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>
|
|
<span class="mim-text-font">
|
|
<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/16/92?start=-3&limit=10&highlight=92">16p13.3</a>
|
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|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr16:2039820-2047834&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'})">16:2,039,820-2,047,834</a> </span>
|
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</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
|
|
|
|
|
|
|
</span>
|
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</p>
|
|
</div>
|
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
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|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/16/92?start=-3&limit=10&highlight=92">
|
|
16p13.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Familial adenomatous polyposis 3
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/616415"> 616415 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
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|
|
|
|
</tr>
|
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|
</tbody>
|
|
</table>
|
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</div>
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</div>
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<div>
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<p>DNA N-glycosylases, or apurinic/apyrimidinic lyases, of the endonuclease III family, such as NTHL1, initiate DNA base excision repair of oxidized ring saturated pyrimidine residues (<a href="#4" class="mim-tip-reference" title="Ocampo, M. T. A., Chaung, W., Marenstein, D. R., Chan, M. K., Altamirano, A., Basu, A. K., Boorstein, R. J., Cunningham, R. P., Teebor, G. W. <strong>Targeted deletion of mNth1 reveals a novel DNA repair enzyme activity.</strong> Molec. Cell. Biol. 22: 6111-6121, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12167705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12167705</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12167705[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.22.17.6111-6121.2002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12167705">Ocampo et al., 2002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12167705" 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="#6" class="mim-tip-reference" title="The European Chromosome 16 Tuberous Sclerosis Consortium. <strong>Identification and characterization of the tuberous sclerosis gene on chromosome 16.</strong> Cell 75: 1305-1315, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8269512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8269512</a>] [<a href="https://doi.org/10.1016/0092-8674(93)90618-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8269512">The European Chromosome 16 Tuberous Sclerosis Consortium (1993)</a> identified a gene, termed OCTS3, that lies next to TSC2 (<a href="/entry/191092">191092</a>) in a head-to-head orientation on chromosome 16. <a href="#1" class="mim-tip-reference" title="Aspinwall, R., Rothwell, D. G., Roldan-Arjona, T., Anselmino, C., Ward, C. J., Cheadle, J. P., Sampson, J. R., Lindahl, T., Harris, P. C., Hickson, I. D. <strong>Cloning and characterization of a functional human homolog of Escherichia coli endonuclease III.</strong> Proc. Nat. Acad. Sci. 94: 109-114, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8990169/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8990169</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=8990169[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.94.1.109" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8990169">Aspinwall et al. (1997)</a> cloned a corresponding cDNA and showed that OCTS3 encodes a human homolog of E. coli endonuclease III. They renamed the human gene NTH1, in reference to the E. coli 'nth' gene. The human NTH1 gene encodes a 312-amino acid polypeptide with a predicted mass of 34.3 kD. When expressed and purified, the protein had the same enzymatic activities as the E. coli enzyme: DNA glycosylase activity on DNA substrates containing oxidized pyrimidine residues, and apurinic/apyrimidinic lyase activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8990169+8269512" 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>Based on peptide sequences of purified bovine endonuclease III and sequences in the expressed sequence tag database (dbEST), <a href="#2" class="mim-tip-reference" title="Hilbert, T. P., Chaung, W., Boorstein, R. J., Cunningham, R. P., Teebor, G. W. <strong>Cloning and expression of the cDNA encoding the human homologue of the DNA repair enzyme, Escherichia coli endonuclease III.</strong> J. Biol. Chem. 272: 6733-6740, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9045706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9045706</a>] [<a href="https://doi.org/10.1074/jbc.272.10.6733" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9045706">Hilbert et al. (1997)</a> also cloned a human NTH1 cDNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9045706" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using Northern blot analysis, <a href="#3" class="mim-tip-reference" title="Imai, K., Sarker, A. H., Akiyama, K., Ikeda, S., Yao, M., Tsutsui, K., Shohmori, T., Seki, S. <strong>Genomic structure and sequence of a human homologue (NTHL1/NTH1) of Escherichia coli endonuclease III with those of the adjacent parts of TSC2 and SLC9A3R2 genes.</strong> Gene 222: 287-295, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9831664/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9831664</a>] [<a href="https://doi.org/10.1016/s0378-1119(98)00485-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9831664">Imai et al. (1998)</a> found ubiquitous but variable expression of a 1.0-kb NTHL1 transcript. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9831664" 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="#3" class="mim-tip-reference" title="Imai, K., Sarker, A. H., Akiyama, K., Ikeda, S., Yao, M., Tsutsui, K., Shohmori, T., Seki, S. <strong>Genomic structure and sequence of a human homologue (NTHL1/NTH1) of Escherichia coli endonuclease III with those of the adjacent parts of TSC2 and SLC9A3R2 genes.</strong> Gene 222: 287-295, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9831664/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9831664</a>] [<a href="https://doi.org/10.1016/s0378-1119(98)00485-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9831664">Imai et al. (1998)</a> cloned the NTHL1 gene and showed that it contains 6 exons spanning approximately 8 kb of genomic DNA. Promoter analysis indicated a lack of TATA and CAAT boxes but the presence of a CpG island with binding sites for several transcription factors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9831664" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#2" class="mim-tip-reference" title="Hilbert, T. P., Chaung, W., Boorstein, R. J., Cunningham, R. P., Teebor, G. W. <strong>Cloning and expression of the cDNA encoding the human homologue of the DNA repair enzyme, Escherichia coli endonuclease III.</strong> J. Biol. Chem. 272: 6733-6740, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9045706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9045706</a>] [<a href="https://doi.org/10.1074/jbc.272.10.6733" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9045706">Hilbert et al. (1997)</a> used fluorescence in situ hybridization to localize the NTHL1 gene to chromosome 16p13.3-p13.2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9045706" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In 7 affected individuals from 3 unrelated families with familial adenomatous polyposis-3 (FAP3; <a href="/entry/616415">616415</a>), <a href="#7" class="mim-tip-reference" title="Weren, R. D. A., Ligtenberg, M. J. L., Kets, C. M., de Voer, R. M., Verwiel, E. T. P., Spruijt, L., van Zelst-Stams, W. A. G., Jongmans, M. C., Gilissen, C., Hehir-Kwa, J. Y., Hoischen, A., Shendure, J., and 9 others. <strong>A germline homozygous mutation in the base-excision repair gene NTHL1 causes adenomatous polyposis and colorectal cancer.</strong> Nature Genet. 47: 668-671, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25938944/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25938944</a>] [<a href="https://doi.org/10.1038/ng.3287" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25938944">Weren et al. (2015)</a> identified a homozygous truncating mutation in the NTHL1 gene (Q90X; <a href="#0001">602656.0001</a>), which encodes a base excision repair gene. The mutation was found by whole-exome sequencing of 51 patients from 48 families with predisposition to colonic adenomatous polyposis, and was confirmed by Sanger sequencing to segregate with the disorder in the 3 families. Analysis of patient cells showed that the mutation resulted in nonsense-mediated mRNA decay, consistent with a loss of function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25938944" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a German woman with FAP3 and multiple additional extracolonic neoplasms, <a href="#5" class="mim-tip-reference" title="Rivera, B., Castellsague, E., Bah, I., and others. <strong>Biallelic NTHL1 mutations in a woman with multiple primary tumors. (Letter)</strong> New Eng. J. Med. 373: 1985-1986, 2015. Note: Full author list online. Erratum: New Eng. J. Med. 373: e33, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26559593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26559593</a>] [<a href="https://doi.org/10.1056/NEJMc1506878" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26559593">Rivera et al. (2015)</a> identified compound heterozygous mutations in the NTHL1 gene (<a href="#0001">602656.0001</a> and <a href="#0002">602656.0002</a>). Six different tumors from the proband were found to carry somatic mutations in driver genes, such as FGFR3 (<a href="/entry/134934">134934</a>). <a href="#5" class="mim-tip-reference" title="Rivera, B., Castellsague, E., Bah, I., and others. <strong>Biallelic NTHL1 mutations in a woman with multiple primary tumors. (Letter)</strong> New Eng. J. Med. 373: 1985-1986, 2015. Note: Full author list online. Erratum: New Eng. J. Med. 373: e33, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26559593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26559593</a>] [<a href="https://doi.org/10.1056/NEJMc1506878" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26559593">Rivera et al. (2015)</a> noted that 6 of the 7 patients reported by <a href="#7" class="mim-tip-reference" title="Weren, R. D. A., Ligtenberg, M. J. L., Kets, C. M., de Voer, R. M., Verwiel, E. T. P., Spruijt, L., van Zelst-Stams, W. A. G., Jongmans, M. C., Gilissen, C., Hehir-Kwa, J. Y., Hoischen, A., Shendure, J., and 9 others. <strong>A germline homozygous mutation in the base-excision repair gene NTHL1 causes adenomatous polyposis and colorectal cancer.</strong> Nature Genet. 47: 668-671, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25938944/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25938944</a>] [<a href="https://doi.org/10.1038/ng.3287" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25938944">Weren et al. (2015)</a> had a diagnosis of multiple primary tumors, suggesting that NTHL1 mutations can cause a wide variety of cancers in addition to colorectal cancer. <a href="#5" class="mim-tip-reference" title="Rivera, B., Castellsague, E., Bah, I., and others. <strong>Biallelic NTHL1 mutations in a woman with multiple primary tumors. (Letter)</strong> New Eng. J. Med. 373: 1985-1986, 2015. Note: Full author list online. Erratum: New Eng. J. Med. 373: e33, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26559593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26559593</a>] [<a href="https://doi.org/10.1056/NEJMc1506878" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26559593">Rivera et al. (2015)</a> suggested the designation 'NTHL1 syndrome' for this cancer predisposition syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=25938944+26559593" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#4" class="mim-tip-reference" title="Ocampo, M. T. A., Chaung, W., Marenstein, D. R., Chan, M. K., Altamirano, A., Basu, A. K., Boorstein, R. J., Cunningham, R. P., Teebor, G. W. <strong>Targeted deletion of mNth1 reveals a novel DNA repair enzyme activity.</strong> Molec. Cell. Biol. 22: 6111-6121, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12167705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12167705</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12167705[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.22.17.6111-6121.2002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12167705">Ocampo et al. (2002)</a> found that the phenotype of Nth1 -/- mice was indistinguishable from that of wildtype mice. They found that loss of Nth1 activity was compensated for by enzymatic activity that recognized oxidized thymine in DNA, particularly when paired with guanine. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12167705" 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>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>2 Selected Examples</a>):</strong>
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<a href="/allelicVariants/602656" class="btn btn-default" role="button"> Table View </a>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=602656[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<strong>.0001 FAMILIAL ADENOMATOUS POLYPOSIS 3</strong>
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NTHL1, GLN90TER
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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> rs150766139 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs150766139;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/rs150766139?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=rs150766139" 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=rs150766139" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000172911 OR RCV000657657 OR RCV000850062 OR RCV003416065" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000172911, RCV000657657, RCV000850062, RCV003416065" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000172911...</a>
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<p>In 7 affected individuals from 3 unrelated families with familial adenomatous polyposis-3 (FAP3; <a href="/entry/616415">616415</a>), <a href="#7" class="mim-tip-reference" title="Weren, R. D. A., Ligtenberg, M. J. L., Kets, C. M., de Voer, R. M., Verwiel, E. T. P., Spruijt, L., van Zelst-Stams, W. A. G., Jongmans, M. C., Gilissen, C., Hehir-Kwa, J. Y., Hoischen, A., Shendure, J., and 9 others. <strong>A germline homozygous mutation in the base-excision repair gene NTHL1 causes adenomatous polyposis and colorectal cancer.</strong> Nature Genet. 47: 668-671, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25938944/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25938944</a>] [<a href="https://doi.org/10.1038/ng.3287" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25938944">Weren et al. (2015)</a> identified a homozygous c.268C-T transition (c.268C-T, NM_002528) in the NTHL1 gene, resulting in a gln90-to-ter (Q90X) substitution. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was filtered against an in-house exome database of 2,037 control individuals. A heterozygous Q90X mutation was found at a frequency of 0.0036 among 2,329 controls and of 0.0015 in the Exome Aggregation Consortium (ExAC) database; the highest prevalence of the mutation was found in individuals of European descent. Analysis of patient cells showed that the mutation resulted in nonsense-mediated mRNA decay, consistent with a loss of function. Genetic analysis of 3 carcinomas and 5 adenomas from different affected individuals showed a nonhypermutated profile enriched for C-to-T transitions, and the carcinomas carried somatic mutations in several genes, including APC (<a href="/entry/611731">611731</a>), TP53 (<a href="/entry/191170">191170</a>), KRAS (<a href="/entry/190070">190070</a>), and PIK3CA (<a href="/entry/171834">171834</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25938944" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0002 FAMILIAL ADENOMATOUS POLYPOSIS 3</strong>
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NTHL1, IVS4DS, G-A, +1
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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> rs372946560 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs372946560;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/rs372946560?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=rs372946560" 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=rs372946560" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000202319 OR RCV000807122 OR RCV003352802" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000202319, RCV000807122, RCV003352802" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000202319...</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a German woman with familial adenomatous polyposis-3 (FAP3; <a href="/entry/616415">616415</a>) and multiple additional extracolonic neoplasms, <a href="#5" class="mim-tip-reference" title="Rivera, B., Castellsague, E., Bah, I., and others. <strong>Biallelic NTHL1 mutations in a woman with multiple primary tumors. (Letter)</strong> New Eng. J. Med. 373: 1985-1986, 2015. Note: Full author list online. Erratum: New Eng. J. Med. 373: e33, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26559593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26559593</a>] [<a href="https://doi.org/10.1056/NEJMc1506878" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26559593">Rivera et al. (2015)</a> identified compound heterozygous mutations in the NTHL1 gene: a c.709+1G-A transition in intron 4 (c.709+1G-A, NM_002528), resulting in a splice site defect that was detectable in patient cells, and Q90X (<a href="#0001">602656.0001</a>). The patient developed colonic adenocarcinoma at age 41, and was later found to have bladder carcinoma, intradermal nevi, meningioma, multiple seborrheic keratoses, basal cell carcinoma, multiple colorectal adenomas, squamous cell carcinoma, and invasive ductal carcinoma. Six different tumors from the proband were found to carry somatic mutations in driver genes, such as FGFR3 (<a href="/entry/134934">134934</a>). She also had a family history of cancer. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26559593" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="references"class="mim-anchor"></a>
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<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span class="mim-font">
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<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
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<ol>
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<a id="1" class="mim-anchor"></a>
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<a id="Aspinwall1997" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Aspinwall, R., Rothwell, D. G., Roldan-Arjona, T., Anselmino, C., Ward, C. J., Cheadle, J. P., Sampson, J. R., Lindahl, T., Harris, P. C., Hickson, I. D.
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<strong>Cloning and characterization of a functional human homolog of Escherichia coli endonuclease III.</strong>
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Proc. Nat. Acad. Sci. 94: 109-114, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8990169/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8990169</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=8990169[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=8990169" 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.94.1.109" target="_blank">Full Text</a>]
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<a id="Hilbert1997" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Hilbert, T. P., Chaung, W., Boorstein, R. J., Cunningham, R. P., Teebor, G. W.
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<strong>Cloning and expression of the cDNA encoding the human homologue of the DNA repair enzyme, Escherichia coli endonuclease III.</strong>
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J. Biol. Chem. 272: 6733-6740, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9045706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9045706</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9045706" 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.272.10.6733" target="_blank">Full Text</a>]
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<a id="3" class="mim-anchor"></a>
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<a id="Imai1998" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Imai, K., Sarker, A. H., Akiyama, K., Ikeda, S., Yao, M., Tsutsui, K., Shohmori, T., Seki, S.
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<strong>Genomic structure and sequence of a human homologue (NTHL1/NTH1) of Escherichia coli endonuclease III with those of the adjacent parts of TSC2 and SLC9A3R2 genes.</strong>
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Gene 222: 287-295, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9831664/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9831664</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9831664" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0378-1119(98)00485-5" target="_blank">Full Text</a>]
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<a id="4" class="mim-anchor"></a>
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<a id="Ocampo2002" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Ocampo, M. T. A., Chaung, W., Marenstein, D. R., Chan, M. K., Altamirano, A., Basu, A. K., Boorstein, R. J., Cunningham, R. P., Teebor, G. W.
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<strong>Targeted deletion of mNth1 reveals a novel DNA repair enzyme activity.</strong>
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Molec. Cell. Biol. 22: 6111-6121, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12167705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12167705</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12167705[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=12167705" 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.22.17.6111-6121.2002" target="_blank">Full Text</a>]
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<a id="5" class="mim-anchor"></a>
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<a id="Rivera2015" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Rivera, B., Castellsague, E., Bah, I., and others.
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<strong>Biallelic NTHL1 mutations in a woman with multiple primary tumors. (Letter)</strong>
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New Eng. J. Med. 373: 1985-1986, 2015. Note: Full author list online. Erratum: New Eng. J. Med. 373: e33, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26559593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26559593</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26559593" 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/10.1056/NEJMc1506878" target="_blank">Full Text</a>]
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<li>
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<a id="6" class="mim-anchor"></a>
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<a id="{The European Chromosome 16 Tuberous Sclerosis Consortium}1993" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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The European Chromosome 16 Tuberous Sclerosis Consortium.
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<strong>Identification and characterization of the tuberous sclerosis gene on chromosome 16.</strong>
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Cell 75: 1305-1315, 1993.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8269512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8269512</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8269512" 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/10.1016/0092-8674(93)90618-z" target="_blank">Full Text</a>]
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<a id="7" class="mim-anchor"></a>
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<a id="Weren2015" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Weren, R. D. A., Ligtenberg, M. J. L., Kets, C. M., de Voer, R. M., Verwiel, E. T. P., Spruijt, L., van Zelst-Stams, W. A. G., Jongmans, M. C., Gilissen, C., Hehir-Kwa, J. Y., Hoischen, A., Shendure, J., and 9 others.
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<strong>A germline homozygous mutation in the base-excision repair gene NTHL1 causes adenomatous polyposis and colorectal cancer.</strong>
|
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Nature Genet. 47: 668-671, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25938944/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25938944</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25938944" 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/ng.3287" 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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Cassandra L. Kniffin - updated : 11/19/2015
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</span>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 6/9/2015<br>Patricia A. Hartz - updated : 8/30/2006<br>Paul J. Converse - updated : 12/12/2001<br>Alan F. Scott - updated : 3/17/1999
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</span>
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</div>
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</div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Jennifer P. Macke : 5/26/1998
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</span>
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</div>
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </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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carol : 08/11/2016
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</span>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 11/20/2015<br>ckniffin : 11/19/2015<br>carol : 6/10/2015<br>mcolton : 6/9/2015<br>ckniffin : 6/9/2015<br>wwang : 9/6/2006<br>terry : 8/30/2006<br>mgross : 12/12/2001<br>carol : 3/17/1999<br>alopez : 5/27/1998<br>alopez : 5/27/1998<br>alopez : 5/26/1998
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<h3>
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<span class="mim-font">
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<strong>*</strong> 602656
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</span>
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</h3>
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<div>
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<h3>
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<span class="mim-font">
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ENDONUCLEASE III-LIKE 1; NTHL1
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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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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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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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ENDONUCLEASE III, E. COLI, HOMOLOG OF; NTH1<br />
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OCTS3
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</span>
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</h4>
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: NTHL1</em></strong>
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</span>
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</p>
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</div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 16p13.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 16:2,039,820-2,047,834 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<tbody>
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<td rowspan="1">
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<span class="mim-font">
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16p13.3
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</td>
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<td>
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<span class="mim-font">
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Familial adenomatous polyposis 3
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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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616415
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tbody>
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</table>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>DNA N-glycosylases, or apurinic/apyrimidinic lyases, of the endonuclease III family, such as NTHL1, initiate DNA base excision repair of oxidized ring saturated pyrimidine residues (Ocampo et al., 2002). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The European Chromosome 16 Tuberous Sclerosis Consortium (1993) identified a gene, termed OCTS3, that lies next to TSC2 (191092) in a head-to-head orientation on chromosome 16. Aspinwall et al. (1997) cloned a corresponding cDNA and showed that OCTS3 encodes a human homolog of E. coli endonuclease III. They renamed the human gene NTH1, in reference to the E. coli 'nth' gene. The human NTH1 gene encodes a 312-amino acid polypeptide with a predicted mass of 34.3 kD. When expressed and purified, the protein had the same enzymatic activities as the E. coli enzyme: DNA glycosylase activity on DNA substrates containing oxidized pyrimidine residues, and apurinic/apyrimidinic lyase activity. </p><p>Based on peptide sequences of purified bovine endonuclease III and sequences in the expressed sequence tag database (dbEST), Hilbert et al. (1997) also cloned a human NTH1 cDNA. </p><p>Using Northern blot analysis, Imai et al. (1998) found ubiquitous but variable expression of a 1.0-kb NTHL1 transcript. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Imai et al. (1998) cloned the NTHL1 gene and showed that it contains 6 exons spanning approximately 8 kb of genomic DNA. Promoter analysis indicated a lack of TATA and CAAT boxes but the presence of a CpG island with binding sites for several transcription factors. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Hilbert et al. (1997) used fluorescence in situ hybridization to localize the NTHL1 gene to chromosome 16p13.3-p13.2. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In 7 affected individuals from 3 unrelated families with familial adenomatous polyposis-3 (FAP3; 616415), Weren et al. (2015) identified a homozygous truncating mutation in the NTHL1 gene (Q90X; 602656.0001), which encodes a base excision repair gene. The mutation was found by whole-exome sequencing of 51 patients from 48 families with predisposition to colonic adenomatous polyposis, and was confirmed by Sanger sequencing to segregate with the disorder in the 3 families. Analysis of patient cells showed that the mutation resulted in nonsense-mediated mRNA decay, consistent with a loss of function. </p><p>In a German woman with FAP3 and multiple additional extracolonic neoplasms, Rivera et al. (2015) identified compound heterozygous mutations in the NTHL1 gene (602656.0001 and 602656.0002). Six different tumors from the proband were found to carry somatic mutations in driver genes, such as FGFR3 (134934). Rivera et al. (2015) noted that 6 of the 7 patients reported by Weren et al. (2015) had a diagnosis of multiple primary tumors, suggesting that NTHL1 mutations can cause a wide variety of cancers in addition to colorectal cancer. Rivera et al. (2015) suggested the designation 'NTHL1 syndrome' for this cancer predisposition syndrome. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Ocampo et al. (2002) found that the phenotype of Nth1 -/- mice was indistinguishable from that of wildtype mice. They found that loss of Nth1 activity was compensated for by enzymatic activity that recognized oxidized thymine in DNA, particularly when paired with guanine. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
|
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</span>
|
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<strong>2 Selected Examples):</strong>
|
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</span>
|
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</h4>
|
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<div>
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<p />
|
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0001 FAMILIAL ADENOMATOUS POLYPOSIS 3</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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NTHL1, GLN90TER
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<br />
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|
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SNP: rs150766139,
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gnomAD: rs150766139,
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ClinVar: RCV000172911, RCV000657657, RCV000850062, RCV003416065
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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 7 affected individuals from 3 unrelated families with familial adenomatous polyposis-3 (FAP3; 616415), Weren et al. (2015) identified a homozygous c.268C-T transition (c.268C-T, NM_002528) in the NTHL1 gene, resulting in a gln90-to-ter (Q90X) substitution. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was filtered against an in-house exome database of 2,037 control individuals. A heterozygous Q90X mutation was found at a frequency of 0.0036 among 2,329 controls and of 0.0015 in the Exome Aggregation Consortium (ExAC) database; the highest prevalence of the mutation was found in individuals of European descent. Analysis of patient cells showed that the mutation resulted in nonsense-mediated mRNA decay, consistent with a loss of function. Genetic analysis of 3 carcinomas and 5 adenomas from different affected individuals showed a nonhypermutated profile enriched for C-to-T transitions, and the carcinomas carried somatic mutations in several genes, including APC (611731), TP53 (191170), KRAS (190070), and PIK3CA (171834). </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>.0002 FAMILIAL ADENOMATOUS POLYPOSIS 3</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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NTHL1, IVS4DS, G-A, +1
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<br />
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SNP: rs372946560,
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gnomAD: rs372946560,
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ClinVar: RCV000202319, RCV000807122, RCV003352802
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a German woman with familial adenomatous polyposis-3 (FAP3; 616415) and multiple additional extracolonic neoplasms, Rivera et al. (2015) identified compound heterozygous mutations in the NTHL1 gene: a c.709+1G-A transition in intron 4 (c.709+1G-A, NM_002528), resulting in a splice site defect that was detectable in patient cells, and Q90X (602656.0001). The patient developed colonic adenocarcinoma at age 41, and was later found to have bladder carcinoma, intradermal nevi, meningioma, multiple seborrheic keratoses, basal cell carcinoma, multiple colorectal adenomas, squamous cell carcinoma, and invasive ductal carcinoma. Six different tumors from the proband were found to carry somatic mutations in driver genes, such as FGFR3 (134934). She also had a family history of cancer. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>REFERENCES</strong>
|
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</span>
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</h4>
|
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<div>
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<p />
|
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
|
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Aspinwall, R., Rothwell, D. G., Roldan-Arjona, T., Anselmino, C., Ward, C. J., Cheadle, J. P., Sampson, J. R., Lindahl, T., Harris, P. C., Hickson, I. D.
|
|
<strong>Cloning and characterization of a functional human homolog of Escherichia coli endonuclease III.</strong>
|
|
Proc. Nat. Acad. Sci. 94: 109-114, 1997.
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[PubMed: 8990169]
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[Full Text: https://doi.org/10.1073/pnas.94.1.109]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Hilbert, T. P., Chaung, W., Boorstein, R. J., Cunningham, R. P., Teebor, G. W.
|
|
<strong>Cloning and expression of the cDNA encoding the human homologue of the DNA repair enzyme, Escherichia coli endonuclease III.</strong>
|
|
J. Biol. Chem. 272: 6733-6740, 1997.
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[PubMed: 9045706]
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[Full Text: https://doi.org/10.1074/jbc.272.10.6733]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Imai, K., Sarker, A. H., Akiyama, K., Ikeda, S., Yao, M., Tsutsui, K., Shohmori, T., Seki, S.
|
|
<strong>Genomic structure and sequence of a human homologue (NTHL1/NTH1) of Escherichia coli endonuclease III with those of the adjacent parts of TSC2 and SLC9A3R2 genes.</strong>
|
|
Gene 222: 287-295, 1998.
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[PubMed: 9831664]
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[Full Text: https://doi.org/10.1016/s0378-1119(98)00485-5]
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Ocampo, M. T. A., Chaung, W., Marenstein, D. R., Chan, M. K., Altamirano, A., Basu, A. K., Boorstein, R. J., Cunningham, R. P., Teebor, G. W.
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<strong>Targeted deletion of mNth1 reveals a novel DNA repair enzyme activity.</strong>
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Molec. Cell. Biol. 22: 6111-6121, 2002.
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[PubMed: 12167705]
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[Full Text: https://doi.org/10.1128/MCB.22.17.6111-6121.2002]
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Rivera, B., Castellsague, E., Bah, I., and others.
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<strong>Biallelic NTHL1 mutations in a woman with multiple primary tumors. (Letter)</strong>
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New Eng. J. Med. 373: 1985-1986, 2015. Note: Full author list online. Erratum: New Eng. J. Med. 373: e33, 2015.
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[PubMed: 26559593]
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[Full Text: https://doi.org/10.1056/NEJMc1506878]
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The European Chromosome 16 Tuberous Sclerosis Consortium.
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<strong>Identification and characterization of the tuberous sclerosis gene on chromosome 16.</strong>
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Cell 75: 1305-1315, 1993.
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[PubMed: 8269512]
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[Full Text: https://doi.org/10.1016/0092-8674(93)90618-z]
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Weren, R. D. A., Ligtenberg, M. J. L., Kets, C. M., de Voer, R. M., Verwiel, E. T. P., Spruijt, L., van Zelst-Stams, W. A. G., Jongmans, M. C., Gilissen, C., Hehir-Kwa, J. Y., Hoischen, A., Shendure, J., and 9 others.
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<strong>A germline homozygous mutation in the base-excision repair gene NTHL1 causes adenomatous polyposis and colorectal cancer.</strong>
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Nature Genet. 47: 668-671, 2015.
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[PubMed: 25938944]
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[Full Text: https://doi.org/10.1038/ng.3287]
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Cassandra L. Kniffin - updated : 11/19/2015<br>Cassandra L. Kniffin - updated : 6/9/2015<br>Patricia A. Hartz - updated : 8/30/2006<br>Paul J. Converse - updated : 12/12/2001<br>Alan F. Scott - updated : 3/17/1999
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