3699 lines
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Entry
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- *613555 - TET METHYLCYTOSINE DIOXYGENASE 3; TET3
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*613555</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>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<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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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/613555">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 panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000187605;t=ENST00000409262" 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=200424" 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=613555" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000187605;t=ENST00000409262" 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_001287491,NM_001366022,XM_011532682,XM_011532683,XM_011532684,XM_011532685,XM_011532687,XM_011532688,XM_011532690,XM_017003566,XM_024452745,XM_024452746,XM_047443659,XM_047443660,XM_047443662,XM_047443664" 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_001287491" 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=613555" 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=19402&isoform_id=19402_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/TET3" 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/2662083,18490118,28194063,62702130,119620108,316990466,566559863,767914129,767914131,767914133,767914136,767914140,767914142,767914146,1034612339,1370476990,1370476992,1478050931,1775786381,2217326238,2217326240,2217326243,2217326249,2462570970,2462570972,2462570974,2462570976,2462570978,2462570980,2462570982,2462570984,2462570986,2462570988,2462570990,2462570992,2462570994,2462570996" 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/O43151" 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=200424" 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=ENSG00000187605;t=ENST00000409262" 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=TET3" 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=TET3" 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+200424" 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/TET3" 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:200424" 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/200424" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr2&hgg_gene=ENST00000652224.1&hgg_start=73983631&hgg_end=74135498&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:28313" 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=613555[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=613555[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/TET3/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000187605" 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=TET3" 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=TET3" 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=TET3" 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=TET3&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/PA162405645" 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:28313" 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/FBgn0263392.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:2446229" 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/TET3#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:2446229" 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/200424/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=200424" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-060526-109" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://reactome.org/content/query?q=TET3&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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613555
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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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TET METHYLCYTOSINE DIOXYGENASE 3; TET3
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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TET ONCOGENE FAMILY, MEMBER 3<br />
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KIAA0401
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
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<span class="mim-text-font">
|
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=TET3" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">TET3</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
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Cytogenetic location: <a href="/geneMap/2/372?start=-3&limit=10&highlight=372">2p13.1</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr2:73983631-74135498&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">2:73,983,631-74,135,498</a> </span>
|
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</em>
|
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</strong>
|
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
|
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<br />
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
|
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<td rowspan="1">
|
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<span class="mim-font">
|
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<a href="/geneMap/2/372?start=-3&limit=10&highlight=372">
|
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2p13.1
|
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</a>
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
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Beck-Fahrner syndrome
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
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<a href="/entry/618798"> 618798 </a>
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/613555" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/613555" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<div>
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<p />
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
|
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
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<strong>TEXT</strong>
|
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</span>
|
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</span>
|
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</h4>
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<div>
|
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<a id="description" class="mim-anchor"></a>
|
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<p>The TET3 gene encodes a methylcytosine dioxygenase that initiates DNA demethylation to regulate gene expression during early zygote formation, embryogenesis, and neuronal differentiation (summary by <a href="#2" class="mim-tip-reference" title="Beck, D. B., Petracovici, A., He, C., Moore, H. W., Louie, R. J., Ansar, M., Douzgou, S., Sithambaram, S., Cottrell, T., Santos-Cortez, R. L. P., Prijoles, E. J., Bend, R., and 20 others. <strong>Delineation of a human mendelian disorder of the DNA demethylation machinery: TET3 deficiency.</strong> Am. J. Hum. Genet. 106: 234-245, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31928709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31928709</a>] [<a href="https://doi.org/10.1016/j.ajhg.2019.12.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31928709">Beck et al., 2020</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31928709" 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>Members of the ten-eleven translocation (TET) gene family, including TET3, play a role in the DNA methylation process (<a href="#9" class="mim-tip-reference" title="Langemeijer, S. M. C., Aslanyan, M. G., Jansen, J. H. <strong>TET proteins in malignant hematopoiesis.</strong> Cell Cycle 8: 4044-4048, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19923888/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19923888</a>] [<a href="https://doi.org/10.4161/cc.8.24.10239" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19923888">Langemeijer et al., 2009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19923888" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By sequencing clones obtained from a size-fractionated brain cDNA library, <a href="#6" class="mim-tip-reference" title="Ishikawa, K., Nagase, T., Nakajima, D., Seki, N., Ohira, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O. <strong>Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro.</strong> DNA Res. 4: 307-313, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9455477/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9455477</a>] [<a href="https://doi.org/10.1093/dnares/4.5.307" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9455477">Ishikawa et al. (1997)</a> cloned partial TET3, which they designated KIAA0401. RT-PCR showed expression in a variety of human tissues, most prominently in brain, placenta, lung, and thymus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9455477" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Langemeijer, S. M. C., Aslanyan, M. G., Jansen, J. H. <strong>TET proteins in malignant hematopoiesis.</strong> Cell Cycle 8: 4044-4048, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19923888/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19923888</a>] [<a href="https://doi.org/10.4161/cc.8.24.10239" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19923888">Langemeijer et al. (2009)</a> noted that the deduced TET3 protein contains 1,660 amino acids and shares 2 C-terminal highly conserved domains, a cys-rich region and a 2OGFeDO homology domain, with TET1 (<a href="/entry/607790">607790</a>) and TET2 (<a href="/entry/612839">612839</a>). By real-time PCR analysis, they demonstrated that TET3, like TET2, is ubiquitously expressed with highest expression in hematopoietic cells, particularly of myeloid and monocytic lineage. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19923888" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a computational search for enzymes that could modify 5-methylcytosine (5mC), <a href="#12" class="mim-tip-reference" title="Tahiliani, M., Koh, K. P., Shen, Y., Pastor, W. A., Bandukwala, H., Brudno, Y., Agarwal, S., Iyer, L. M., Liu, D. R., Aravind, L., Rao, A. <strong>Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1.</strong> Science 324: 930-935, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19372391/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19372391</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19372391[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/10.1126/science.1170116" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19372391">Tahiliani et al. (2009)</a> identified TET proteins as mammalian homologs of the trypanosome proteins JBP1 and JBP2, which have been proposed to oxidize the 5-methyl group of thymine. They showed that TET1, a fusion partner of the MLL gene in acute myeloid leukemia, is a 2-oxoglutarate (2OG)- and Fe(II)-dependent enzyme that catalyzes conversion of 5mC to 5-hydroxymethylcytosine (5hmC) in cultured cells and in vitro. 5hmC is present in the genome of mouse embryonic stem cells, and 5hmC levels decrease upon RNA interference-mediated depletion of TET1. Thus, <a href="#12" class="mim-tip-reference" title="Tahiliani, M., Koh, K. P., Shen, Y., Pastor, W. A., Bandukwala, H., Brudno, Y., Agarwal, S., Iyer, L. M., Liu, D. R., Aravind, L., Rao, A. <strong>Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1.</strong> Science 324: 930-935, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19372391/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19372391</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19372391[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/10.1126/science.1170116" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19372391">Tahiliani et al. (2009)</a> concluded that TET proteins have potential roles in epigenetic regulation through modification of 5mC to 5hmC. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19372391" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Ito, S., D'Alessio, A. C., Taranova, O. V., Hong, K., Sowers, L. C., Zhang, Y. <strong>Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification.</strong> Nature 466: 1129-1133, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20639862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20639862</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20639862[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09303" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20639862">Ito et al. (2010)</a> extended the study of <a href="#12" class="mim-tip-reference" title="Tahiliani, M., Koh, K. P., Shen, Y., Pastor, W. A., Bandukwala, H., Brudno, Y., Agarwal, S., Iyer, L. M., Liu, D. R., Aravind, L., Rao, A. <strong>Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1.</strong> Science 324: 930-935, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19372391/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19372391</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19372391[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/10.1126/science.1170116" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19372391">Tahiliani et al. (2009)</a> by demonstrating that all 3 mouse TET proteins, Tet1, Tet2, and Tet3, can also catalyze the conversion of 5mC to 5hmC. Tet1 has an important role in mouse embryonic stem cell maintenance through maintaining the expression of Nanog (<a href="/entry/607937">607937</a>) in embryonic stem cells. Downregulation of Nanog via Tet1 knockdown correlated with methylation of the Nanog promoter, supporting a role for Tet1 in regulating DNA methylation status. Furthermore, knockdown of Tet1 in preimplantation embryos resulted in a bias towards trophectoderm differentiation. Thus, <a href="#7" class="mim-tip-reference" title="Ito, S., D'Alessio, A. C., Taranova, O. V., Hong, K., Sowers, L. C., Zhang, Y. <strong>Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification.</strong> Nature 466: 1129-1133, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20639862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20639862</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20639862[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09303" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20639862">Ito et al. (2010)</a> concluded that their studies not only uncovered the enzymatic activity of the Tet proteins, but also demonstrated a role for Tet1 in embryonic stem cell maintenance and inner cell mass cell specification. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19372391+20639862" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Ito, S., Shen, L., Dai, Q., Wu, S. C., Collins, L. B., Swenberg, J. A., He, C., Zhang, Y. <strong>Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine.</strong> Science 333: 1300-1303, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21778364/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21778364</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21778364[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/10.1126/science.1210597" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21778364">Ito et al. (2011)</a> showed that, in addition to 5hmC, the Tet proteins can generate 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) from 5mC in an enzymatic activity-dependent manner. Furthermore, <a href="#8" class="mim-tip-reference" title="Ito, S., Shen, L., Dai, Q., Wu, S. C., Collins, L. B., Swenberg, J. A., He, C., Zhang, Y. <strong>Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine.</strong> Science 333: 1300-1303, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21778364/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21778364</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21778364[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/10.1126/science.1210597" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21778364">Ito et al. (2011)</a> revealed the presence of 5fC and 5caC in genomic DNA of mouse embryonic stem cells and mouse organs. The genomic content of 5hmC, 5fC, and 5caC can be increased or reduced through overexpression or depletion of Tet proteins. Thus, <a href="#8" class="mim-tip-reference" title="Ito, S., Shen, L., Dai, Q., Wu, S. C., Collins, L. B., Swenberg, J. A., He, C., Zhang, Y. <strong>Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine.</strong> Science 333: 1300-1303, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21778364/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21778364</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21778364[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/10.1126/science.1210597" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21778364">Ito et al. (2011)</a> concluded that they identified 2 previously unknown cytosine derivatives in genomic DNA as the products of Tet proteins, and raised the possibility that DNA demethylation may occur through Tet-catalyzed oxidation followed by decarboxylation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21778364" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="He, Y.-F., Li, B.-Z., Li, Z., Liu, P., Wang, Y., Tang, Q., Ding, J., Jia, Y., Chen, Z., Li, L., Sun, Y., Li, X., Dai, Q., Song, C.-X., Zhang, K., He, C., Xu, G.-L. <strong>Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA.</strong> Science 333: 1303-1307, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21817016/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21817016</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21817016[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/10.1126/science.1210944" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21817016">He et al. (2011)</a> demonstrated that 5mC and 5hmC in DNA are oxidized to 5caC by Tet dioxygenases in vitro and in cultured cells. 5caC is specifically recognized and excised by thymine-DNA glycosylase (TDG; <a href="/entry/601423">601423</a>). Depletion of TDG in mouse embryonic stem cells leads to accumulation of 5caC to a readily detectable level. <a href="#5" class="mim-tip-reference" title="He, Y.-F., Li, B.-Z., Li, Z., Liu, P., Wang, Y., Tang, Q., Ding, J., Jia, Y., Chen, Z., Li, L., Sun, Y., Li, X., Dai, Q., Song, C.-X., Zhang, K., He, C., Xu, G.-L. <strong>Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA.</strong> Science 333: 1303-1307, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21817016/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21817016</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21817016[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/10.1126/science.1210944" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21817016">He et al. (2011)</a> concluded that oxidation of 5mC by Tet proteins followed by TDG-mediated base excision of 5caC constitutes a pathway for active DNA demethylation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21817016" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Gu, T.-P., Guo, F., Yang, H., Wu, H.-P., Xu, G.-F., Liu, W., Xie, Z.-G., Shi, L., He, X., Jin, S., Iqbal, K., Shi, Y. G., Deng, Z., Szabo, P. E., Pfeifer, G. P., Li, J., Xu, G.-L. <strong>The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes.</strong> Nature 477: 606-610, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21892189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21892189</a>] [<a href="https://doi.org/10.1038/nature10443" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21892189">Gu et al. (2011)</a> reported that, within mouse zygotes, oxidation of 5-methylcytosine (5mC) occurs on the paternal genome, changing 5mC into 5-hydroxymethylcytosine (5hmC). Furthermore, they demonstrated that the dioxygenase Tet3 is enriched specifically in the male pronucleus. In Tet3-deficient zygotes from conditional knockout mice, paternal genome conversion of 5mC into 5hmC failed to occur and the level of 5mC remains constant. Deficiency of Tet3 also impeded the demethylation process of the paternal Oct4 (<a href="/entry/164177">164177</a>) and Nanog genes and delayed the subsequent activation of a paternally derived Oct4 transgene in early embryos. Female mice depleted of Tet3 in the germline showed severely reduced fecundity, and their heterozygous mutant offspring lacking maternal Tet3 suffered an increased incidence of developmental failure. Oocytes lacking Tet3 also seemed to have a reduced ability to reprogram the injected nuclei from somatic cells. Therefore, <a href="#4" class="mim-tip-reference" title="Gu, T.-P., Guo, F., Yang, H., Wu, H.-P., Xu, G.-F., Liu, W., Xie, Z.-G., Shi, L., He, X., Jin, S., Iqbal, K., Shi, Y. G., Deng, Z., Szabo, P. E., Pfeifer, G. P., Li, J., Xu, G.-L. <strong>The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes.</strong> Nature 477: 606-610, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21892189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21892189</a>] [<a href="https://doi.org/10.1038/nature10443" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21892189">Gu et al. (2011)</a> concluded that Tet3-mediated DNA hydroxylation is involved in epigenetic reprogramming of the zygotic paternal DNA following natural fertilization and may also contribute to somatic cell nuclear reprogramming during animal cloning. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21892189" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By analyzing RNA-sequencing data, <a href="#13" class="mim-tip-reference" title="Yan, H., Wang, Y., Qu, X., Li, J., Hale, J., Huang, Y., An, C., Papoin, J., Guo, X., Chen, L., Kang, Q., Li, W., Schulz, V. P., Gallagher, P. G., Hillyer, C. D., Mohandas, N., An, X. <strong>Distinct roles for TET family proteins in regulating human erythropoiesis.</strong> Blood 129: 2002-2012, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28167661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28167661</a>] [<a href="https://doi.org/10.1182/blood-2016-08-736587" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28167661">Yan et al. (2017)</a> found that TET3 was the most abundantly expressed TET family member during human erythropoiesis and that its expression was significantly upregulated at late stages of erythroid differentiation. In contrast, TET2 was expressed at a lower but constant level throughout erythropoiesis. TET3 knockdown predominantly affected gene expression of late-stage erythroblasts and impaired terminal erythroid differentiation. TET3 knockdown impaired enucleation and led to generation of bi- or multinucleated polychromatic and orthochromatic erythroblasts, resulting in reduced cell growth and increased apoptosis. KLHDC8B (<a href="/entry/613169">613169</a>) knockdown mimicked the TET3 knockdown-induced defects in enucleation and nuclear abnormalities, but ectopic expression of KLHDC8B only partially rescued the bi- or multinucleation defect in TET3-knockdown cells. In contrast with TET3, TET2 knockdown led to increased growth and delayed differentiation of erythroid progenitors, resulting in their accumulation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28167661" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Li, D., Cao, T., Sun, X., Jin, S., Xie, D., Huang, X., Yang, X., Carmichael, G. G., Taylor, H. S., Diano, S., Huang, Y. <strong>Hepatic TET3 contributes to type-2 diabetes by inducing the HNF4-alpha fetal isoform.</strong> Nature Commun. 11: 342, 2020. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31953394/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31953394</a>] [<a href="https://doi.org/10.1038/s41467-019-14185-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31953394">Li et al. (2020)</a> found that upregulated hepatic expression of the long noncoding RNA (lncRNA) H19 (<a href="/entry/103280">103280</a>) promoted Tet3 expression in mouse hepatocytes, likely by inhibiting Let7 (see <a href="/entry/605386">605386</a>)-mediated Tet3 repression. Upregulated Tet3 expression, in turn, promoted hepatic glucose production. Tet3 expression was positively correlated with expression of the P2 promoter-specific isoform of Hnf4-alpha (HNF4A; <a href="/entry/600281">600281</a>). Tet3 induced Hnf4-alpha expression by directly binding and demethylating the P2 promoter. Tet3 was recruited to the P2 promoter via physical interaction with Foxa2 (<a href="/entry/600288">600288</a>). Induction of the P2-specific isoform of Hnf4-alpha mediated Tet3-dependent hepatic glucose production. Knockdown of Tet3 or the P2-specific Hnf4-alpha isoform in liver reduced hepatic glucose production and thereby improved glucose homeostasis in both dietary and genetic mouse models of type-2 diabetes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31953394" 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="#11" class="mim-tip-reference" title="Stumpf, A. M. <strong>Personal Communication.</strong> Baltimore, Md. 06/17/2020."None>Stumpf (2020)</a> mapped the TET3 gene to chromosome 2p13.1 based on an alignment of the TET3 sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=BC022243" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">BC022243</a>) with the genomic sequence (GRCh38).</p>
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In 5 patients from 3 unrelated families (families 1-3) with autosomal recessive Beck-Fahrner syndrome (BEFAHRS; <a href="/entry/618798">618798</a>), <a href="#2" class="mim-tip-reference" title="Beck, D. B., Petracovici, A., He, C., Moore, H. W., Louie, R. J., Ansar, M., Douzgou, S., Sithambaram, S., Cottrell, T., Santos-Cortez, R. L. P., Prijoles, E. J., Bend, R., and 20 others. <strong>Delineation of a human mendelian disorder of the DNA demethylation machinery: TET3 deficiency.</strong> Am. J. Hum. Genet. 106: 234-245, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31928709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31928709</a>] [<a href="https://doi.org/10.1016/j.ajhg.2019.12.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31928709">Beck et al. (2020)</a> identified homozygous or compound heterozygous missense mutations in the TET3 gene (<a href="#0001">613555.0001</a>-<a href="#0005">613555.0005</a>) that segregated with the disorder in the families. All but 1 mutation (R752C) occurred at highly conserved residues in the catalytic domain and resulted in decreased TET3 catalytic activity as measured in vitro by 5hmC production in HEK293 cells; the findings indicated that most of the mutations were hypomorphic. All but 1 of the 5 patients were female. Five of the 6 parents, who were heterozygous mutation carriers, showed similar, but milder symptoms. <a href="#2" class="mim-tip-reference" title="Beck, D. B., Petracovici, A., He, C., Moore, H. W., Louie, R. J., Ansar, M., Douzgou, S., Sithambaram, S., Cottrell, T., Santos-Cortez, R. L. P., Prijoles, E. J., Bend, R., and 20 others. <strong>Delineation of a human mendelian disorder of the DNA demethylation machinery: TET3 deficiency.</strong> Am. J. Hum. Genet. 106: 234-245, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31928709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31928709</a>] [<a href="https://doi.org/10.1016/j.ajhg.2019.12.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31928709">Beck et al. (2020)</a> also reported 4 additional unrelated male patients (families 4, 5, 6, and 8) and a father-son duo (family 7) with autosomal dominant BEFAHRS who carried heterozygous TET3 mutations (see, e.g., <a href="#0006">613555.0006</a>-<a href="#0009">613555.0009</a>). Three of the 5 heterozygous mutations were predicted to result in a nonsense or frameshift mutation, suggesting a loss-of-function effect with haploinsufficiency. However, 2 of these mutations occurred in the last exon, raising the possibility that a truncated protein could be produced and have a dominant-negative effect. The 2 remaining patients carried heterozygous missense variants. Functional studies of the heterozygous variants and studies of patient cells were not performed. All patients, who were ascertained through the GeneMatcher program, underwent exome sequencing with Sanger confirmation in the respective laboratories. None of the variants were found in the gnomAD database except R752C. Nonsense and frameshift mutations were only observed in the heterozygous state, suggesting that some residual TET3 activity is required for viability. The findings also suggested a dose-dependent mechanism, such that if TET3 activity falls below a certain threshold, developmental phenotypes will result, regardless of whether reduced TET3 activity is caused by heterozygous loss-of-function alleles or by biallelic hypomorphic missense alleles. <a href="#2" class="mim-tip-reference" title="Beck, D. B., Petracovici, A., He, C., Moore, H. W., Louie, R. J., Ansar, M., Douzgou, S., Sithambaram, S., Cottrell, T., Santos-Cortez, R. L. P., Prijoles, E. J., Bend, R., and 20 others. <strong>Delineation of a human mendelian disorder of the DNA demethylation machinery: TET3 deficiency.</strong> Am. J. Hum. Genet. 106: 234-245, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31928709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31928709</a>] [<a href="https://doi.org/10.1016/j.ajhg.2019.12.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31928709">Beck et al. (2020)</a> noted that all but 1 of the patients with biallelic mutations were female, whereas all patients with heterozygous mutations were male, suggesting the possibility of sex-specific differences. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31928709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Exclusion Studies</em></strong></p><p>
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<a href="#1" class="mim-tip-reference" title="Abdel-Wahab, O., Mullally, A., Hedvat, C., Garcia-Manero, G., Patel, J., Wadleigh, M., Malinge, S., Yao, J., Kilpivaara, O., Bhat, R., Huberman, K., Thomas, S., and 12 others. <strong>Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies.</strong> Blood 114: 144-147, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19420352/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19420352</a>] [<a href="https://doi.org/10.1182/blood-2009-03-210039" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19420352">Abdel-Wahab et al. (2009)</a> did not find somatic mutations in the TET3 gene among 96 patients with myeloproliferative neoplasms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19420352" 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="Dai, H.-Q., Wang, B.-A., Yang, L., Chen, J.-J., Zhu, G.-C., Sun, M.-L., Ge, H., Wang, R., Chapman, D. L., Tang, F., Sun, X., Xu, G.-L. <strong>TET-mediated DNA demethylation controls gastrulation by regulating Lefty-Nodal signalling.</strong> Nature 538: 528-532, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27760115/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27760115</a>] [<a href="https://doi.org/10.1038/nature20095" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27760115">Dai et al. (2016)</a> demonstrated that inactivation of all 3 Tet genes in mice leads to gastrulation phenotypes, including primitive streak patterning defects in association with impaired maturation of axial mesoderm and failed specification of paraxial mesoderm, mimicking phenotypes in embryos with gain-of-function Nodal (<a href="/entry/601265">601265</a>) signaling. Introduction of a single mutant allele of Nodal in the Tet mutant background partially restored patterning, suggesting that hyperactive Nodal signaling contributes to the gastrulation failure of Tet mutants. Increased Nodal signaling is probably due to diminished expression of the Lefty1 (<a href="/entry/603037">603037</a>) and Lefty2 (<a href="/entry/601877">601877</a>) genes, which encode inhibitors of Nodal signaling. Moreover, reduction in Lefty gene expression is linked to elevated DNA methylation, as both Lefty-Nodal signaling and normal morphogenesis are largely restored in Tet-deficient embryos when the Dnmt3a (<a href="/entry/602769">602769</a>) and Dnmt3b (<a href="/entry/602900">602900</a>) genes are disrupted. Additionally, a point mutation in Tet that specifically abolishes the dioxygenase activity causes similar morphologic and molecular abnormalities as the null mutation. <a href="#3" class="mim-tip-reference" title="Dai, H.-Q., Wang, B.-A., Yang, L., Chen, J.-J., Zhu, G.-C., Sun, M.-L., Ge, H., Wang, R., Chapman, D. L., Tang, F., Sun, X., Xu, G.-L. <strong>TET-mediated DNA demethylation controls gastrulation by regulating Lefty-Nodal signalling.</strong> Nature 538: 528-532, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27760115/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27760115</a>] [<a href="https://doi.org/10.1038/nature20095" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27760115">Dai et al. (2016)</a> concluded that TET-mediated oxidation of 5-methylcytosine modulates Lefty-Nodal signaling by promoting demethylation in opposition to methylation by DNMT3A and DNMT3B. The authors also concluded that their findings revealed a fundamental epigenetic mechanism featuring dynamic DNA methylation and demethylation crucial to regulation of key signaling pathways in early body plan formation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27760115" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs1174857008 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1174857008;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/rs1174857008?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=rs1174857008" 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=rs1174857008" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a 7-year-old Caucasian girl (family 1) with autosomal recessive Beck-Fahrner syndrome (BEFAHRS; <a href="/entry/618798">618798</a>), <a href="#2" class="mim-tip-reference" title="Beck, D. B., Petracovici, A., He, C., Moore, H. W., Louie, R. J., Ansar, M., Douzgou, S., Sithambaram, S., Cottrell, T., Santos-Cortez, R. L. P., Prijoles, E. J., Bend, R., and 20 others. <strong>Delineation of a human mendelian disorder of the DNA demethylation machinery: TET3 deficiency.</strong> Am. J. Hum. Genet. 106: 234-245, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31928709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31928709</a>] [<a href="https://doi.org/10.1016/j.ajhg.2019.12.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31928709">Beck et al. (2020)</a> identified compound heterozygous missense mutations in the TET3 gene: a c.3265G-A transition (c.3265G-A, NM_001287491.1), resulting in a val1089-to-met (V1089M) substitution at a highly conserved residue in the catalytic dioxygenase domain, and a c.2254C-T transition, resulting in an arg752-to-cys (R752C; <a href="#0002">613555.0002</a>) substitution at a less well conserved residue upstream of the catalytic domain. The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, were each inherited from a mildly affected parent. V1089M was not found in the gnomAD database, whereas R752C was found 29 times in the heterozygous state. In vitro functional expression studies in HEK293 cells showed that the V1089M mutation caused decreased TET3 catalytic activity as measured by decreased 5hmc production compared to controls, whereas R752C was similar to wildtype, suggesting the possibility that the V1089M variant was solely responsible for the phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31928709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs534089911 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs534089911;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/rs534089911?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=rs534089911" 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=rs534089911" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV001007566 OR RCV001257922 OR RCV004030286 OR RCV004697023" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001007566, RCV001257922, RCV004030286, RCV004697023" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001007566...</a>
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<p>For discussion of the c.2254C-T transition (c.2254C-T, NM_001287491.1) in the TET3 gene, resulting in an arg752-to-cys (R752C) substitution, that was found in compound heterozygous state in a patient with autosomal recessive Beck-Fahrner syndrome (BEFAHRS; <a href="/entry/618798">618798</a>) by <a href="#2" class="mim-tip-reference" title="Beck, D. B., Petracovici, A., He, C., Moore, H. W., Louie, R. J., Ansar, M., Douzgou, S., Sithambaram, S., Cottrell, T., Santos-Cortez, R. L. P., Prijoles, E. J., Bend, R., and 20 others. <strong>Delineation of a human mendelian disorder of the DNA demethylation machinery: TET3 deficiency.</strong> Am. J. Hum. Genet. 106: 234-245, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31928709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31928709</a>] [<a href="https://doi.org/10.1016/j.ajhg.2019.12.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31928709">Beck et al. (2020)</a>, see <a href="#0001">613555.0001</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31928709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 BECK-FAHRNER SYNDROME, AUTOSOMAL RECESSIVE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1573906351 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1573906351;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1573906351" 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=rs1573906351" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV001007567 OR RCV001257924" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001007567, RCV001257924" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001007567...</a>
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<p>In a 3-year-old Caucasian girl (family 2) with autosomal recessive Beck-Fahrner syndrome (BEFAHRS; <a href="/entry/618798">618798</a>), <a href="#2" class="mim-tip-reference" title="Beck, D. B., Petracovici, A., He, C., Moore, H. W., Louie, R. J., Ansar, M., Douzgou, S., Sithambaram, S., Cottrell, T., Santos-Cortez, R. L. P., Prijoles, E. J., Bend, R., and 20 others. <strong>Delineation of a human mendelian disorder of the DNA demethylation machinery: TET3 deficiency.</strong> Am. J. Hum. Genet. 106: 234-245, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31928709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31928709</a>] [<a href="https://doi.org/10.1016/j.ajhg.2019.12.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31928709">Beck et al. (2020)</a> identified compound heterozygous missense mutations in the TET3 gene: a c.3215T-G transversion (c.3215T-G, NM_001287491.1), resulting in a phe1072-to-cys (F1072C) substitution, and a c.3226G-A transition, resulting in an ala1076-to-thr (A1076T; <a href="#0004">613555.0004</a>) substitution. The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, were each inherited from a mildly affected parent. Both mutations occurred at conserved residues in the catalytic dioxygenase domain, and neither was present in the gnomAD database. In vitro functional expression studies in HEK293 cells showed that both resulted in decreased TET3 catalytic activity as measured by decreased 5hmc production compared to controls, consistent with hypomorphic alleles. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31928709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 BECK-FAHRNER SYNDROME, AUTOSOMAL RECESSIVE</strong>
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TET3, ALA1076THR
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1573906389 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1573906389;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1573906389" 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=rs1573906389" 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=RCV001007568 OR RCV001257925" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001007568, RCV001257925" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001007568...</a>
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<p>For discussion of the c.3226G-A transition (c.3226G-A, NM_001287491.1) in the TET3 gene, resulting in an ala1076-to-thr (A1076T) substitution, that was found in compound heterozygous state in a patient with autosomal recessive Beck-Fahrner syndrome (BEFAHRS; <a href="/entry/618798">618798</a>) by <a href="#2" class="mim-tip-reference" title="Beck, D. B., Petracovici, A., He, C., Moore, H. W., Louie, R. J., Ansar, M., Douzgou, S., Sithambaram, S., Cottrell, T., Santos-Cortez, R. L. P., Prijoles, E. J., Bend, R., and 20 others. <strong>Delineation of a human mendelian disorder of the DNA demethylation machinery: TET3 deficiency.</strong> Am. J. Hum. Genet. 106: 234-245, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31928709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31928709</a>] [<a href="https://doi.org/10.1016/j.ajhg.2019.12.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31928709">Beck et al. (2020)</a>, see <a href="#0003">613555.0003</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31928709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 BECK-FAHRNER SYNDROME, AUTOSOMAL RECESSIVE</strong>
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TET3, VAL908LEU
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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> rs1227643933 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1227643933;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/rs1227643933?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=rs1227643933" 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=rs1227643933" 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=RCV001007569 OR RCV001257926 OR RCV001291082" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001007569, RCV001257926, RCV001291082" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001007569...</a>
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<p>In 3 adult sibs, born of consanguineous Asian parents (family 3), with autosomal recessive Beck-Fahrner syndrome (BEFAHRS; <a href="/entry/618798">618798</a>), <a href="#2" class="mim-tip-reference" title="Beck, D. B., Petracovici, A., He, C., Moore, H. W., Louie, R. J., Ansar, M., Douzgou, S., Sithambaram, S., Cottrell, T., Santos-Cortez, R. L. P., Prijoles, E. J., Bend, R., and 20 others. <strong>Delineation of a human mendelian disorder of the DNA demethylation machinery: TET3 deficiency.</strong> Am. J. Hum. Genet. 106: 234-245, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31928709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31928709</a>] [<a href="https://doi.org/10.1016/j.ajhg.2019.12.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31928709">Beck et al. (2020)</a> identified a homozygous c.2722G-T transversion (c.2722G-T, NM_001287491.1) in the TET3 gene, resulting in a val908-to-leu (V908L) substitution at a highly conserved residue in the catalytic domain. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the gnomAD database. Each parent was a heterozygous carrier for the mutation, and the mother showed similar but milder features. In vitro functional expression studies in HEK293 cells showed that the mutation resulted in decreased TET3 catalytic activity as measured by decreased 5hmc production compared to controls, consistent with a hypomorphic allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31928709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0006" class="mim-anchor"></a>
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<strong>.0006 BECK-FAHRNER SYNDROME, AUTOSOMAL DOMINANT</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1573856970 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1573856970;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1573856970" 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=rs1573856970" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV001007570 OR RCV001257927 OR RCV002549265" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001007570, RCV001257927, RCV002549265" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001007570...</a>
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<p>In an 11-month-old Caucasian male (family 4) with autosomal dominant Beck-Fahrner syndrome (BEFAHRS; <a href="/entry/618798">618798</a>), <a href="#2" class="mim-tip-reference" title="Beck, D. B., Petracovici, A., He, C., Moore, H. W., Louie, R. J., Ansar, M., Douzgou, S., Sithambaram, S., Cottrell, T., Santos-Cortez, R. L. P., Prijoles, E. J., Bend, R., and 20 others. <strong>Delineation of a human mendelian disorder of the DNA demethylation machinery: TET3 deficiency.</strong> Am. J. Hum. Genet. 106: 234-245, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31928709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31928709</a>] [<a href="https://doi.org/10.1016/j.ajhg.2019.12.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31928709">Beck et al. (2020)</a> identified a de novo heterozygous c.2552C-T transition (c.2552C-T, NM_001287491.1) in the TET3 gene, resulting in a thr851-to-met (T851M) substitution at a conserved residue in the catalytic domain. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed, but it was predicted to result in haploinsufficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31928709" 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="0007" class="mim-anchor"></a>
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<strong>.0007 BECK-FAHRNER SYNDROME, AUTOSOMAL DOMINANT</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1572907595 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1572907595;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1572907595" 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=rs1572907595" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV001007571 OR RCV001257928" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001007571, RCV001257928" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001007571...</a>
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<p>In a 7-year-old boy (family 5), born of unrelated parents from Morocco and the West Indies, with autosomal dominant Beck-Fahrner syndrome (BEFAHRS; <a href="/entry/618798">618798</a>), <a href="#2" class="mim-tip-reference" title="Beck, D. B., Petracovici, A., He, C., Moore, H. W., Louie, R. J., Ansar, M., Douzgou, S., Sithambaram, S., Cottrell, T., Santos-Cortez, R. L. P., Prijoles, E. J., Bend, R., and 20 others. <strong>Delineation of a human mendelian disorder of the DNA demethylation machinery: TET3 deficiency.</strong> Am. J. Hum. Genet. 106: 234-245, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31928709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31928709</a>] [<a href="https://doi.org/10.1016/j.ajhg.2019.12.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31928709">Beck et al. (2020)</a> identified a de novo heterozygous c.5083C-T transition (c.5083C-T, NM_001287491.1) in the last exon of the TET3 gene, resulting in a gln1695-to-ter (Q1695X) substitution in the catalytic domain. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed. The variant was predicted either to result in haploinsufficiency or to escape nonsense-mediated mRNA and possibly produce a truncated protein with a dominant-negative effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31928709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0008 BECK-FAHRNER SYNDROME, AUTOSOMAL DOMINANT</strong>
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TET3, 7-BP DEL, NT4977
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1572907400 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1572907400;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1572907400" 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=rs1572907400" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV001007572 OR RCV001257930" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001007572, RCV001257930" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001007572...</a>
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<p>In a father and son with autosomal dominant Beck-Fahrner syndrome (BEFAHRS; <a href="/entry/618798">618798</a>), <a href="#2" class="mim-tip-reference" title="Beck, D. B., Petracovici, A., He, C., Moore, H. W., Louie, R. J., Ansar, M., Douzgou, S., Sithambaram, S., Cottrell, T., Santos-Cortez, R. L. P., Prijoles, E. J., Bend, R., and 20 others. <strong>Delineation of a human mendelian disorder of the DNA demethylation machinery: TET3 deficiency.</strong> Am. J. Hum. Genet. 106: 234-245, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31928709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31928709</a>] [<a href="https://doi.org/10.1016/j.ajhg.2019.12.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31928709">Beck et al. (2020)</a> identified a heterozygous 7-bp deletion (c.4977_4983del, NM_001287491.1) in the last exon of the TET3 gene, predicted to result in a frameshift and premature termination (His1660ProfsTer52) in the catalytic domain. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed. The variant was predicted either to result in haploinsufficiency or to escape nonsense-mediated mRNA and possibly produce a truncated protein with a dominant-negative effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31928709" 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>.0009 BECK-FAHRNER SYNDROME, AUTOSOMAL DOMINANT</strong>
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TET3, 1-BP DEL, 1215A
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1573779765 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1573779765;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1573779765" 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=rs1573779765" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV001007573 OR RCV001257931" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001007573, RCV001257931" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001007573...</a>
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<p>In a 10-year-old boy of Ashkenazi Jewish descent (family 8) with autosomal dominant Beck-Fahrner syndrome (BEFAHRS; <a href="/entry/618798">618798</a>), <a href="#2" class="mim-tip-reference" title="Beck, D. B., Petracovici, A., He, C., Moore, H. W., Louie, R. J., Ansar, M., Douzgou, S., Sithambaram, S., Cottrell, T., Santos-Cortez, R. L. P., Prijoles, E. J., Bend, R., and 20 others. <strong>Delineation of a human mendelian disorder of the DNA demethylation machinery: TET3 deficiency.</strong> Am. J. Hum. Genet. 106: 234-245, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31928709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31928709</a>] [<a href="https://doi.org/10.1016/j.ajhg.2019.12.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31928709">Beck et al. (2020)</a> identified a de novo heterozygous 1-bp deletion (c.1215delA, NM_001287491.1) in the TET3 gene, predicted to result in a frameshift and premature termination (Trp406GlyfsTer135). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed, but it was predicted to result in haploinsufficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31928709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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<a id="1" class="mim-anchor"></a>
|
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<a id="Abdel-Wahab2009" class="mim-anchor"></a>
|
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Abdel-Wahab, O., Mullally, A., Hedvat, C., Garcia-Manero, G., Patel, J., Wadleigh, M., Malinge, S., Yao, J., Kilpivaara, O., Bhat, R., Huberman, K., Thomas, S., and 12 others.
|
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<strong>Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies.</strong>
|
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Blood 114: 144-147, 2009.
|
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19420352/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19420352</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19420352" 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/10.1182/blood-2009-03-210039" target="_blank">Full Text</a>]
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Beck, D. B., Petracovici, A., He, C., Moore, H. W., Louie, R. J., Ansar, M., Douzgou, S., Sithambaram, S., Cottrell, T., Santos-Cortez, R. L. P., Prijoles, E. J., Bend, R., and 20 others.
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<strong>Delineation of a human mendelian disorder of the DNA demethylation machinery: TET3 deficiency.</strong>
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Am. J. Hum. Genet. 106: 234-245, 2020.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31928709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31928709</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31928709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ajhg.2019.12.007" target="_blank">Full Text</a>]
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<a id="Dai2016" class="mim-anchor"></a>
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Dai, H.-Q., Wang, B.-A., Yang, L., Chen, J.-J., Zhu, G.-C., Sun, M.-L., Ge, H., Wang, R., Chapman, D. L., Tang, F., Sun, X., Xu, G.-L.
|
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<strong>TET-mediated DNA demethylation controls gastrulation by regulating Lefty-Nodal signalling.</strong>
|
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Nature 538: 528-532, 2016.
|
|
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27760115/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27760115</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27760115" 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/nature20095" target="_blank">Full Text</a>]
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Gu, T.-P., Guo, F., Yang, H., Wu, H.-P., Xu, G.-F., Liu, W., Xie, Z.-G., Shi, L., He, X., Jin, S., Iqbal, K., Shi, Y. G., Deng, Z., Szabo, P. E., Pfeifer, G. P., Li, J., Xu, G.-L.
|
|
<strong>The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes.</strong>
|
|
Nature 477: 606-610, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21892189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21892189</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21892189" 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/nature10443" target="_blank">Full Text</a>]
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He, Y.-F., Li, B.-Z., Li, Z., Liu, P., Wang, Y., Tang, Q., Ding, J., Jia, Y., Chen, Z., Li, L., Sun, Y., Li, X., Dai, Q., Song, C.-X., Zhang, K., He, C., Xu, G.-L.
|
|
<strong>Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA.</strong>
|
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Science 333: 1303-1307, 2011.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21817016/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21817016</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21817016[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=21817016" 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/10.1126/science.1210944" target="_blank">Full Text</a>]
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Ishikawa, K., Nagase, T., Nakajima, D., Seki, N., Ohira, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O.
|
|
<strong>Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro.</strong>
|
|
DNA Res. 4: 307-313, 1997.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9455477/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9455477</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9455477" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/dnares/4.5.307" target="_blank">Full Text</a>]
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Ito, S., D'Alessio, A. C., Taranova, O. V., Hong, K., Sowers, L. C., Zhang, Y.
|
|
<strong>Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification.</strong>
|
|
Nature 466: 1129-1133, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20639862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20639862</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20639862[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=20639862" 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/nature09303" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="8" class="mim-anchor"></a>
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<a id="Ito2011" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Ito, S., Shen, L., Dai, Q., Wu, S. C., Collins, L. B., Swenberg, J. A., He, C., Zhang, Y.
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<strong>Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine.</strong>
|
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Science 333: 1300-1303, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21778364/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21778364</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21778364[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=21778364" 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/10.1126/science.1210597" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="9" class="mim-anchor"></a>
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<a id="Langemeijer2009" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Langemeijer, S. M. C., Aslanyan, M. G., Jansen, J. H.
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<strong>TET proteins in malignant hematopoiesis.</strong>
|
|
Cell Cycle 8: 4044-4048, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19923888/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19923888</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19923888" 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/10.4161/cc.8.24.10239" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="10" class="mim-anchor"></a>
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<a id="Li2020" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Li, D., Cao, T., Sun, X., Jin, S., Xie, D., Huang, X., Yang, X., Carmichael, G. G., Taylor, H. S., Diano, S., Huang, Y.
|
|
<strong>Hepatic TET3 contributes to type-2 diabetes by inducing the HNF4-alpha fetal isoform.</strong>
|
|
Nature Commun. 11: 342, 2020. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31953394/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31953394</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31953394" 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/s41467-019-14185-z" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="11" class="mim-anchor"></a>
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<a id="Stumpf2020" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Stumpf, A. M.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 06/17/2020.
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</p>
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</div>
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</li>
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<li>
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<a id="12" class="mim-anchor"></a>
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<a id="Tahiliani2009" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tahiliani, M., Koh, K. P., Shen, Y., Pastor, W. A., Bandukwala, H., Brudno, Y., Agarwal, S., Iyer, L. M., Liu, D. R., Aravind, L., Rao, A.
|
|
<strong>Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1.</strong>
|
|
Science 324: 930-935, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19372391/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19372391</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19372391[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=19372391" 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/10.1126/science.1170116" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="13" class="mim-anchor"></a>
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<a id="Yan2017" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yan, H., Wang, Y., Qu, X., Li, J., Hale, J., Huang, Y., An, C., Papoin, J., Guo, X., Chen, L., Kang, Q., Li, W., Schulz, V. P., Gallagher, P. G., Hillyer, C. D., Mohandas, N., An, X.
|
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<strong>Distinct roles for TET family proteins in regulating human erythropoiesis.</strong>
|
|
Blood 129: 2002-2012, 2017.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28167661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28167661</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28167661" 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/10.1182/blood-2016-08-736587" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Anne M. Stumpf - updated : 06/17/2020
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Bao Lige - updated : 06/16/2020<br>Cassandra L. Kniffin - updated : 03/03/2020<br>Ada Hamosh - updated : 05/13/2019<br>Ada Hamosh - updated : 3/7/2012<br>Ada Hamosh - updated : 9/21/2011<br>Cassandra L. Kniffin - updated : 10/25/2010<br>Ada Hamosh - updated : 9/14/2010
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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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Cassandra L. Kniffin : 9/8/2010
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 03/25/2021
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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alopez : 06/17/2020<br>mgross : 06/16/2020<br>alopez : 03/04/2020<br>ckniffin : 03/03/2020<br>carol : 05/14/2019<br>alopez : 05/13/2019<br>alopez : 05/13/2019<br>alopez : 05/13/2019<br>alopez : 03/09/2012<br>alopez : 3/9/2012<br>terry : 3/7/2012<br>alopez : 9/23/2011<br>terry : 9/21/2011<br>terry : 9/21/2011<br>terry : 12/21/2010<br>wwang : 10/29/2010<br>ckniffin : 10/25/2010<br>alopez : 9/15/2010<br>terry : 9/14/2010<br>wwang : 9/8/2010<br>ckniffin : 9/8/2010
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 613555
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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TET METHYLCYTOSINE DIOXYGENASE 3; TET3
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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TET ONCOGENE FAMILY, MEMBER 3<br />
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KIAA0401
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: TET3</em></strong>
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</span>
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</p>
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</div>
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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: 2p13.1
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Genomic coordinates <span class="small">(GRCh38)</span> : 2:73,983,631-74,135,498 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
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2p13.1
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</span>
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</td>
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<td>
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<span class="mim-font">
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Beck-Fahrner syndrome
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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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618798
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant; Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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<div>
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<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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<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>The TET3 gene encodes a methylcytosine dioxygenase that initiates DNA demethylation to regulate gene expression during early zygote formation, embryogenesis, and neuronal differentiation (summary by Beck et al., 2020). </p><p>Members of the ten-eleven translocation (TET) gene family, including TET3, play a role in the DNA methylation process (Langemeijer et al., 2009). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By sequencing clones obtained from a size-fractionated brain cDNA library, Ishikawa et al. (1997) cloned partial TET3, which they designated KIAA0401. RT-PCR showed expression in a variety of human tissues, most prominently in brain, placenta, lung, and thymus. </p><p>Langemeijer et al. (2009) noted that the deduced TET3 protein contains 1,660 amino acids and shares 2 C-terminal highly conserved domains, a cys-rich region and a 2OGFeDO homology domain, with TET1 (607790) and TET2 (612839). By real-time PCR analysis, they demonstrated that TET3, like TET2, is ubiquitously expressed with highest expression in hematopoietic cells, particularly of myeloid and monocytic lineage. </p>
|
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</span>
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<div>
|
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<br />
|
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Gene Function</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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|
<p>In a computational search for enzymes that could modify 5-methylcytosine (5mC), Tahiliani et al. (2009) identified TET proteins as mammalian homologs of the trypanosome proteins JBP1 and JBP2, which have been proposed to oxidize the 5-methyl group of thymine. They showed that TET1, a fusion partner of the MLL gene in acute myeloid leukemia, is a 2-oxoglutarate (2OG)- and Fe(II)-dependent enzyme that catalyzes conversion of 5mC to 5-hydroxymethylcytosine (5hmC) in cultured cells and in vitro. 5hmC is present in the genome of mouse embryonic stem cells, and 5hmC levels decrease upon RNA interference-mediated depletion of TET1. Thus, Tahiliani et al. (2009) concluded that TET proteins have potential roles in epigenetic regulation through modification of 5mC to 5hmC. </p><p>Ito et al. (2010) extended the study of Tahiliani et al. (2009) by demonstrating that all 3 mouse TET proteins, Tet1, Tet2, and Tet3, can also catalyze the conversion of 5mC to 5hmC. Tet1 has an important role in mouse embryonic stem cell maintenance through maintaining the expression of Nanog (607937) in embryonic stem cells. Downregulation of Nanog via Tet1 knockdown correlated with methylation of the Nanog promoter, supporting a role for Tet1 in regulating DNA methylation status. Furthermore, knockdown of Tet1 in preimplantation embryos resulted in a bias towards trophectoderm differentiation. Thus, Ito et al. (2010) concluded that their studies not only uncovered the enzymatic activity of the Tet proteins, but also demonstrated a role for Tet1 in embryonic stem cell maintenance and inner cell mass cell specification. </p><p>Ito et al. (2011) showed that, in addition to 5hmC, the Tet proteins can generate 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) from 5mC in an enzymatic activity-dependent manner. Furthermore, Ito et al. (2011) revealed the presence of 5fC and 5caC in genomic DNA of mouse embryonic stem cells and mouse organs. The genomic content of 5hmC, 5fC, and 5caC can be increased or reduced through overexpression or depletion of Tet proteins. Thus, Ito et al. (2011) concluded that they identified 2 previously unknown cytosine derivatives in genomic DNA as the products of Tet proteins, and raised the possibility that DNA demethylation may occur through Tet-catalyzed oxidation followed by decarboxylation. </p><p>He et al. (2011) demonstrated that 5mC and 5hmC in DNA are oxidized to 5caC by Tet dioxygenases in vitro and in cultured cells. 5caC is specifically recognized and excised by thymine-DNA glycosylase (TDG; 601423). Depletion of TDG in mouse embryonic stem cells leads to accumulation of 5caC to a readily detectable level. He et al. (2011) concluded that oxidation of 5mC by Tet proteins followed by TDG-mediated base excision of 5caC constitutes a pathway for active DNA demethylation. </p><p>Gu et al. (2011) reported that, within mouse zygotes, oxidation of 5-methylcytosine (5mC) occurs on the paternal genome, changing 5mC into 5-hydroxymethylcytosine (5hmC). Furthermore, they demonstrated that the dioxygenase Tet3 is enriched specifically in the male pronucleus. In Tet3-deficient zygotes from conditional knockout mice, paternal genome conversion of 5mC into 5hmC failed to occur and the level of 5mC remains constant. Deficiency of Tet3 also impeded the demethylation process of the paternal Oct4 (164177) and Nanog genes and delayed the subsequent activation of a paternally derived Oct4 transgene in early embryos. Female mice depleted of Tet3 in the germline showed severely reduced fecundity, and their heterozygous mutant offspring lacking maternal Tet3 suffered an increased incidence of developmental failure. Oocytes lacking Tet3 also seemed to have a reduced ability to reprogram the injected nuclei from somatic cells. Therefore, Gu et al. (2011) concluded that Tet3-mediated DNA hydroxylation is involved in epigenetic reprogramming of the zygotic paternal DNA following natural fertilization and may also contribute to somatic cell nuclear reprogramming during animal cloning. </p><p>By analyzing RNA-sequencing data, Yan et al. (2017) found that TET3 was the most abundantly expressed TET family member during human erythropoiesis and that its expression was significantly upregulated at late stages of erythroid differentiation. In contrast, TET2 was expressed at a lower but constant level throughout erythropoiesis. TET3 knockdown predominantly affected gene expression of late-stage erythroblasts and impaired terminal erythroid differentiation. TET3 knockdown impaired enucleation and led to generation of bi- or multinucleated polychromatic and orthochromatic erythroblasts, resulting in reduced cell growth and increased apoptosis. KLHDC8B (613169) knockdown mimicked the TET3 knockdown-induced defects in enucleation and nuclear abnormalities, but ectopic expression of KLHDC8B only partially rescued the bi- or multinucleation defect in TET3-knockdown cells. In contrast with TET3, TET2 knockdown led to increased growth and delayed differentiation of erythroid progenitors, resulting in their accumulation. </p><p>Li et al. (2020) found that upregulated hepatic expression of the long noncoding RNA (lncRNA) H19 (103280) promoted Tet3 expression in mouse hepatocytes, likely by inhibiting Let7 (see 605386)-mediated Tet3 repression. Upregulated Tet3 expression, in turn, promoted hepatic glucose production. Tet3 expression was positively correlated with expression of the P2 promoter-specific isoform of Hnf4-alpha (HNF4A; 600281). Tet3 induced Hnf4-alpha expression by directly binding and demethylating the P2 promoter. Tet3 was recruited to the P2 promoter via physical interaction with Foxa2 (600288). Induction of the P2-specific isoform of Hnf4-alpha mediated Tet3-dependent hepatic glucose production. Knockdown of Tet3 or the P2-specific Hnf4-alpha isoform in liver reduced hepatic glucose production and thereby improved glucose homeostasis in both dietary and genetic mouse models of type-2 diabetes. </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>Stumpf (2020) mapped the TET3 gene to chromosome 2p13.1 based on an alignment of the TET3 sequence (GenBank BC022243) with the genomic sequence (GRCh38).</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Beck-Fahrner Syndrome</em></strong></p><p>
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In 5 patients from 3 unrelated families (families 1-3) with autosomal recessive Beck-Fahrner syndrome (BEFAHRS; 618798), Beck et al. (2020) identified homozygous or compound heterozygous missense mutations in the TET3 gene (613555.0001-613555.0005) that segregated with the disorder in the families. All but 1 mutation (R752C) occurred at highly conserved residues in the catalytic domain and resulted in decreased TET3 catalytic activity as measured in vitro by 5hmC production in HEK293 cells; the findings indicated that most of the mutations were hypomorphic. All but 1 of the 5 patients were female. Five of the 6 parents, who were heterozygous mutation carriers, showed similar, but milder symptoms. Beck et al. (2020) also reported 4 additional unrelated male patients (families 4, 5, 6, and 8) and a father-son duo (family 7) with autosomal dominant BEFAHRS who carried heterozygous TET3 mutations (see, e.g., 613555.0006-613555.0009). Three of the 5 heterozygous mutations were predicted to result in a nonsense or frameshift mutation, suggesting a loss-of-function effect with haploinsufficiency. However, 2 of these mutations occurred in the last exon, raising the possibility that a truncated protein could be produced and have a dominant-negative effect. The 2 remaining patients carried heterozygous missense variants. Functional studies of the heterozygous variants and studies of patient cells were not performed. All patients, who were ascertained through the GeneMatcher program, underwent exome sequencing with Sanger confirmation in the respective laboratories. None of the variants were found in the gnomAD database except R752C. Nonsense and frameshift mutations were only observed in the heterozygous state, suggesting that some residual TET3 activity is required for viability. The findings also suggested a dose-dependent mechanism, such that if TET3 activity falls below a certain threshold, developmental phenotypes will result, regardless of whether reduced TET3 activity is caused by heterozygous loss-of-function alleles or by biallelic hypomorphic missense alleles. Beck et al. (2020) noted that all but 1 of the patients with biallelic mutations were female, whereas all patients with heterozygous mutations were male, suggesting the possibility of sex-specific differences. </p><p><strong><em>Exclusion Studies</em></strong></p><p>
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Abdel-Wahab et al. (2009) did not find somatic mutations in the TET3 gene among 96 patients with myeloproliferative neoplasms. </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>Dai et al. (2016) demonstrated that inactivation of all 3 Tet genes in mice leads to gastrulation phenotypes, including primitive streak patterning defects in association with impaired maturation of axial mesoderm and failed specification of paraxial mesoderm, mimicking phenotypes in embryos with gain-of-function Nodal (601265) signaling. Introduction of a single mutant allele of Nodal in the Tet mutant background partially restored patterning, suggesting that hyperactive Nodal signaling contributes to the gastrulation failure of Tet mutants. Increased Nodal signaling is probably due to diminished expression of the Lefty1 (603037) and Lefty2 (601877) genes, which encode inhibitors of Nodal signaling. Moreover, reduction in Lefty gene expression is linked to elevated DNA methylation, as both Lefty-Nodal signaling and normal morphogenesis are largely restored in Tet-deficient embryos when the Dnmt3a (602769) and Dnmt3b (602900) genes are disrupted. Additionally, a point mutation in Tet that specifically abolishes the dioxygenase activity causes similar morphologic and molecular abnormalities as the null mutation. Dai et al. (2016) concluded that TET-mediated oxidation of 5-methylcytosine modulates Lefty-Nodal signaling by promoting demethylation in opposition to methylation by DNMT3A and DNMT3B. The authors also concluded that their findings revealed a fundamental epigenetic mechanism featuring dynamic DNA methylation and demethylation crucial to regulation of key signaling pathways in early body plan formation. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>9 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 BECK-FAHRNER SYNDROME, AUTOSOMAL RECESSIVE</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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TET3, VAL1089MET
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<br />
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SNP: rs1174857008,
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gnomAD: rs1174857008,
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ClinVar: RCV001007565, RCV001257923
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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 7-year-old Caucasian girl (family 1) with autosomal recessive Beck-Fahrner syndrome (BEFAHRS; 618798), Beck et al. (2020) identified compound heterozygous missense mutations in the TET3 gene: a c.3265G-A transition (c.3265G-A, NM_001287491.1), resulting in a val1089-to-met (V1089M) substitution at a highly conserved residue in the catalytic dioxygenase domain, and a c.2254C-T transition, resulting in an arg752-to-cys (R752C; 613555.0002) substitution at a less well conserved residue upstream of the catalytic domain. The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, were each inherited from a mildly affected parent. V1089M was not found in the gnomAD database, whereas R752C was found 29 times in the heterozygous state. In vitro functional expression studies in HEK293 cells showed that the V1089M mutation caused decreased TET3 catalytic activity as measured by decreased 5hmc production compared to controls, whereas R752C was similar to wildtype, suggesting the possibility that the V1089M variant was solely responsible for the phenotype. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 BECK-FAHRNER SYNDROME, AUTOSOMAL RECESSIVE</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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TET3, ARG752CYS
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<br />
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SNP: rs534089911,
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gnomAD: rs534089911,
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ClinVar: RCV001007566, RCV001257922, RCV004030286, RCV004697023
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the c.2254C-T transition (c.2254C-T, NM_001287491.1) in the TET3 gene, resulting in an arg752-to-cys (R752C) substitution, that was found in compound heterozygous state in a patient with autosomal recessive Beck-Fahrner syndrome (BEFAHRS; 618798) by Beck et al. (2020), see 613555.0001. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0003 BECK-FAHRNER SYNDROME, AUTOSOMAL RECESSIVE</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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TET3, PHE1072CYS
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<br />
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SNP: rs1573906351,
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ClinVar: RCV001007567, RCV001257924
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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 3-year-old Caucasian girl (family 2) with autosomal recessive Beck-Fahrner syndrome (BEFAHRS; 618798), Beck et al. (2020) identified compound heterozygous missense mutations in the TET3 gene: a c.3215T-G transversion (c.3215T-G, NM_001287491.1), resulting in a phe1072-to-cys (F1072C) substitution, and a c.3226G-A transition, resulting in an ala1076-to-thr (A1076T; 613555.0004) substitution. The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, were each inherited from a mildly affected parent. Both mutations occurred at conserved residues in the catalytic dioxygenase domain, and neither was present in the gnomAD database. In vitro functional expression studies in HEK293 cells showed that both resulted in decreased TET3 catalytic activity as measured by decreased 5hmc production compared to controls, consistent with hypomorphic alleles. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0004 BECK-FAHRNER SYNDROME, AUTOSOMAL RECESSIVE</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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TET3, ALA1076THR
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<br />
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SNP: rs1573906389,
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ClinVar: RCV001007568, RCV001257925
|
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</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the c.3226G-A transition (c.3226G-A, NM_001287491.1) in the TET3 gene, resulting in an ala1076-to-thr (A1076T) substitution, that was found in compound heterozygous state in a patient with autosomal recessive Beck-Fahrner syndrome (BEFAHRS; 618798) by Beck et al. (2020), see 613555.0003. </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 BECK-FAHRNER SYNDROME, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
|
TET3, VAL908LEU
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|
<br />
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|
|
SNP: rs1227643933,
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|
|
gnomAD: rs1227643933,
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|
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ClinVar: RCV001007569, RCV001257926, RCV001291082
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|
|
|
|
|
</span>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 adult sibs, born of consanguineous Asian parents (family 3), with autosomal recessive Beck-Fahrner syndrome (BEFAHRS; 618798), Beck et al. (2020) identified a homozygous c.2722G-T transversion (c.2722G-T, NM_001287491.1) in the TET3 gene, resulting in a val908-to-leu (V908L) substitution at a highly conserved residue in the catalytic domain. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the gnomAD database. Each parent was a heterozygous carrier for the mutation, and the mother showed similar but milder features. In vitro functional expression studies in HEK293 cells showed that the mutation resulted in decreased TET3 catalytic activity as measured by decreased 5hmc production compared to controls, consistent with a hypomorphic allele. </p>
|
|
</span>
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|
</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 BECK-FAHRNER SYNDROME, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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|
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TET3, THR851MET
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<br />
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|
|
SNP: rs1573856970,
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|
|
ClinVar: RCV001007570, RCV001257927, RCV002549265
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|
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In an 11-month-old Caucasian male (family 4) with autosomal dominant Beck-Fahrner syndrome (BEFAHRS; 618798), Beck et al. (2020) identified a de novo heterozygous c.2552C-T transition (c.2552C-T, NM_001287491.1) in the TET3 gene, resulting in a thr851-to-met (T851M) substitution at a conserved residue in the catalytic domain. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed, but it was predicted to result in haploinsufficiency. </p>
|
|
</span>
|
|
</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>.0007 BECK-FAHRNER SYNDROME, AUTOSOMAL DOMINANT</strong>
|
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</span>
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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TET3, GLN1695TER
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<br />
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SNP: rs1572907595,
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ClinVar: RCV001007571, RCV001257928
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 7-year-old boy (family 5), born of unrelated parents from Morocco and the West Indies, with autosomal dominant Beck-Fahrner syndrome (BEFAHRS; 618798), Beck et al. (2020) identified a de novo heterozygous c.5083C-T transition (c.5083C-T, NM_001287491.1) in the last exon of the TET3 gene, resulting in a gln1695-to-ter (Q1695X) substitution in the catalytic domain. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed. The variant was predicted either to result in haploinsufficiency or to escape nonsense-mediated mRNA and possibly produce a truncated protein with a dominant-negative effect. </p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0008 BECK-FAHRNER SYNDROME, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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TET3, 7-BP DEL, NT4977
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<br />
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SNP: rs1572907400,
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ClinVar: RCV001007572, RCV001257930
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<p>In a father and son with autosomal dominant Beck-Fahrner syndrome (BEFAHRS; 618798), Beck et al. (2020) identified a heterozygous 7-bp deletion (c.4977_4983del, NM_001287491.1) in the last exon of the TET3 gene, predicted to result in a frameshift and premature termination (His1660ProfsTer52) in the catalytic domain. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed. The variant was predicted either to result in haploinsufficiency or to escape nonsense-mediated mRNA and possibly produce a truncated protein with a dominant-negative effect. </p>
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<span class="mim-font">
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<strong>.0009 BECK-FAHRNER SYNDROME, AUTOSOMAL DOMINANT</strong>
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TET3, 1-BP DEL, 1215A
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<br />
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SNP: rs1573779765,
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ClinVar: RCV001007573, RCV001257931
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<p>In a 10-year-old boy of Ashkenazi Jewish descent (family 8) with autosomal dominant Beck-Fahrner syndrome (BEFAHRS; 618798), Beck et al. (2020) identified a de novo heterozygous 1-bp deletion (c.1215delA, NM_001287491.1) in the TET3 gene, predicted to result in a frameshift and premature termination (Trp406GlyfsTer135). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed, but it was predicted to result in haploinsufficiency. </p>
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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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<ol>
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<li>
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<p class="mim-text-font">
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Abdel-Wahab, O., Mullally, A., Hedvat, C., Garcia-Manero, G., Patel, J., Wadleigh, M., Malinge, S., Yao, J., Kilpivaara, O., Bhat, R., Huberman, K., Thomas, S., and 12 others.
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<strong>Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies.</strong>
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Blood 114: 144-147, 2009.
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[PubMed: 19420352]
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[Full Text: https://doi.org/10.1182/blood-2009-03-210039]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Beck, D. B., Petracovici, A., He, C., Moore, H. W., Louie, R. J., Ansar, M., Douzgou, S., Sithambaram, S., Cottrell, T., Santos-Cortez, R. L. P., Prijoles, E. J., Bend, R., and 20 others.
|
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<strong>Delineation of a human mendelian disorder of the DNA demethylation machinery: TET3 deficiency.</strong>
|
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Am. J. Hum. Genet. 106: 234-245, 2020.
|
|
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[PubMed: 31928709]
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[Full Text: https://doi.org/10.1016/j.ajhg.2019.12.007]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Dai, H.-Q., Wang, B.-A., Yang, L., Chen, J.-J., Zhu, G.-C., Sun, M.-L., Ge, H., Wang, R., Chapman, D. L., Tang, F., Sun, X., Xu, G.-L.
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<strong>TET-mediated DNA demethylation controls gastrulation by regulating Lefty-Nodal signalling.</strong>
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Nature 538: 528-532, 2016.
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[PubMed: 27760115]
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[Full Text: https://doi.org/10.1038/nature20095]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Gu, T.-P., Guo, F., Yang, H., Wu, H.-P., Xu, G.-F., Liu, W., Xie, Z.-G., Shi, L., He, X., Jin, S., Iqbal, K., Shi, Y. G., Deng, Z., Szabo, P. E., Pfeifer, G. P., Li, J., Xu, G.-L.
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<strong>The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes.</strong>
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Nature 477: 606-610, 2011.
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[PubMed: 21892189]
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[Full Text: https://doi.org/10.1038/nature10443]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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He, Y.-F., Li, B.-Z., Li, Z., Liu, P., Wang, Y., Tang, Q., Ding, J., Jia, Y., Chen, Z., Li, L., Sun, Y., Li, X., Dai, Q., Song, C.-X., Zhang, K., He, C., Xu, G.-L.
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<strong>Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA.</strong>
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Science 333: 1303-1307, 2011.
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[PubMed: 21817016]
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[Full Text: https://doi.org/10.1126/science.1210944]
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<li>
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<p class="mim-text-font">
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Ishikawa, K., Nagase, T., Nakajima, D., Seki, N., Ohira, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O.
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<strong>Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro.</strong>
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DNA Res. 4: 307-313, 1997.
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[PubMed: 9455477]
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[Full Text: https://doi.org/10.1093/dnares/4.5.307]
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Ito, S., D'Alessio, A. C., Taranova, O. V., Hong, K., Sowers, L. C., Zhang, Y.
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<strong>Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification.</strong>
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Nature 466: 1129-1133, 2010.
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[PubMed: 20639862]
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[Full Text: https://doi.org/10.1038/nature09303]
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<p class="mim-text-font">
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Ito, S., Shen, L., Dai, Q., Wu, S. C., Collins, L. B., Swenberg, J. A., He, C., Zhang, Y.
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<strong>Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine.</strong>
|
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Science 333: 1300-1303, 2011.
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[PubMed: 21778364]
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[Full Text: https://doi.org/10.1126/science.1210597]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Langemeijer, S. M. C., Aslanyan, M. G., Jansen, J. H.
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<strong>TET proteins in malignant hematopoiesis.</strong>
|
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Cell Cycle 8: 4044-4048, 2009.
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[PubMed: 19923888]
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[Full Text: https://doi.org/10.4161/cc.8.24.10239]
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<li>
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<p class="mim-text-font">
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Li, D., Cao, T., Sun, X., Jin, S., Xie, D., Huang, X., Yang, X., Carmichael, G. G., Taylor, H. S., Diano, S., Huang, Y.
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<strong>Hepatic TET3 contributes to type-2 diabetes by inducing the HNF4-alpha fetal isoform.</strong>
|
|
Nature Commun. 11: 342, 2020. Note: Electronic Article.
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[PubMed: 31953394]
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[Full Text: https://doi.org/10.1038/s41467-019-14185-z]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Stumpf, A. M.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 06/17/2020.
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Tahiliani, M., Koh, K. P., Shen, Y., Pastor, W. A., Bandukwala, H., Brudno, Y., Agarwal, S., Iyer, L. M., Liu, D. R., Aravind, L., Rao, A.
|
|
<strong>Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1.</strong>
|
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Science 324: 930-935, 2009.
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[PubMed: 19372391]
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[Full Text: https://doi.org/10.1126/science.1170116]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Yan, H., Wang, Y., Qu, X., Li, J., Hale, J., Huang, Y., An, C., Papoin, J., Guo, X., Chen, L., Kang, Q., Li, W., Schulz, V. P., Gallagher, P. G., Hillyer, C. D., Mohandas, N., An, X.
|
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<strong>Distinct roles for TET family proteins in regulating human erythropoiesis.</strong>
|
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Blood 129: 2002-2012, 2017.
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[PubMed: 28167661]
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[Full Text: https://doi.org/10.1182/blood-2016-08-736587]
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</ol>
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<br />
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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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Anne M. Stumpf - updated : 06/17/2020<br>Bao Lige - updated : 06/16/2020<br>Cassandra L. Kniffin - updated : 03/03/2020<br>Ada Hamosh - updated : 05/13/2019<br>Ada Hamosh - updated : 3/7/2012<br>Ada Hamosh - updated : 9/21/2011<br>Cassandra L. Kniffin - updated : 10/25/2010<br>Ada Hamosh - updated : 9/14/2010
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Cassandra L. Kniffin : 9/8/2010
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carol : 03/25/2021<br>alopez : 06/17/2020<br>mgross : 06/16/2020<br>alopez : 03/04/2020<br>ckniffin : 03/03/2020<br>carol : 05/14/2019<br>alopez : 05/13/2019<br>alopez : 05/13/2019<br>alopez : 05/13/2019<br>alopez : 03/09/2012<br>alopez : 3/9/2012<br>terry : 3/7/2012<br>alopez : 9/23/2011<br>terry : 9/21/2011<br>terry : 9/21/2011<br>terry : 12/21/2010<br>wwang : 10/29/2010<br>ckniffin : 10/25/2010<br>alopez : 9/15/2010<br>terry : 9/14/2010<br>wwang : 9/8/2010<br>ckniffin : 9/8/2010
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