3192 lines
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Entry
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- *300269 - HISTONE DEACETYLASE 8; HDAC8
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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">*300269</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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</li>
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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="#biochemicalFeatures">Biochemical Features</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<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/300269">Table View</a>
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</li>
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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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</nav>
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</div>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000147099;t=ENST00000373573" 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=55869" 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=300269" 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=ENSG00000147099;t=ENST00000373573" 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_001166418,NM_001166419,NM_001166420,NM_001166422,NM_001166448,NM_001410725,NM_001410727,NM_001410728,NM_001410729,NM_001410730,NM_018486,NR_051952,XM_017029640,XM_017029643,XM_017029644,XM_017029645,XM_047442252,XM_047442255,XM_047442256,XM_047442257,XR_938402" 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_018486" 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=300269" 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=02227&isoform_id=02227_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/HDAC8" 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/7710996,8118721,8132878,8923769,13182769,29839394,30046561,119592227,119592228,119592229,119592230,194374839,194378882,194383768,194384994,262072965,262073088,262073092,262073100,262073108,1370521764,2217393199,2217393205,2217393207,2217393209,2217393211,2217393213,2217393216,2286439396,2286439444,2286439477,2286439479,2286439500,2462630135,2462630138,2462630140,2462630142,2462630144,2462630146,2462630148,2462630151" 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/Q9BY41" 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=55869" 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=ENSG00000147099;t=ENST00000373573" 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=HDAC8" 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=HDAC8" 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+55869" 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/HDAC8" 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:55869" 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/55869" 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=chrX&hgg_gene=ENST00000648922.1&hgg_start=72329516&hgg_end=72572843&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:13315" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:13315" 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=300269[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=300269[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/HDAC8/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/ENSG00000147099" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.gwascentral.org/search?q=HDAC8" 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=HDAC8" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="http://www.LOVD.nl/HDAC8" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=HDAC8&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/PA37766" 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:13315" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1917565" 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/HDAC8#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:1917565" 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/55869/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=55869" 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-040426-2772" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:55869" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=HDAC8&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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300269
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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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HISTONE DEACETYLASE 8; HDAC8
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=HDAC8" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">HDAC8</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/X/421?start=-3&limit=10&highlight=421">Xq13.1</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chrX:72329516-72572843&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'})">X:72,329,516-72,572,843</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/X/421?start=-3&limit=10&highlight=421">
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Xq13.1
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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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Cornelia de Lange syndrome 5
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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/300882"> 300882 </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="X-linked dominant">XLD</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/300269" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/300269" 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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<p>Reversible acetylation of N-terminal histone tails is a key determinant of gene expression, with hyperacetylation resulting in transcriptional activation, and deacetylation correlating with transcriptional silencing. The level of histone acetylation is determined by the opposing activities of histone acetyltransferases (see HAT1, <a href="/entry/603053">603053</a>) and deacetylases (see HDAC1, <a href="/entry/601241">601241</a>). HDACs are divided into 2 classes: class I, which contains HDACs similar to HDAC1, and class II, which contains HDACs whose C termini share homology with yeast Hda1 (e.g., HDAC4, <a href="/entry/605314">605314</a>). HDAC8 is a class I HDAC (<a href="#6" class="mim-tip-reference" title="Van den Wyngaert, I., de Vries, W., Kremer, A., Neefs, J.-M., Verhasselt, P., Luyten, W. H. M. L., Kass, S. U. <strong>Cloning and characterization of human histone deacetylase 8.</strong> FEBS Lett. 478: 77-83, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10922473/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10922473</a>] [<a href="https://doi.org/10.1016/s0014-5793(00)01813-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10922473">Van den Wyngaert et al., 2000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10922473" 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 searching an EST database for sequences similar to HDAC1, HDAC2, and HDAC3, followed by 5-prime and 3-prime RACE, <a href="#4" class="mim-tip-reference" title="Hu, E., Chen, Z., Fredrickson, T., Zhu, Y., Kirkpatrick, R., Zhang, G.-F., Johanson, K., Sung, C.-M., Liu, R., Winkler, J. <strong>Cloning and characterization of a novel human class I histone deacetylase that functions as a transcription repressor.</strong> J. Biol. Chem. 275: 15254-15264, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10748112/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10748112</a>] [<a href="https://doi.org/10.1074/jbc.M908988199" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10748112">Hu et al. (2000)</a> and <a href="#6" class="mim-tip-reference" title="Van den Wyngaert, I., de Vries, W., Kremer, A., Neefs, J.-M., Verhasselt, P., Luyten, W. H. M. L., Kass, S. U. <strong>Cloning and characterization of human histone deacetylase 8.</strong> FEBS Lett. 478: 77-83, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10922473/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10922473</a>] [<a href="https://doi.org/10.1016/s0014-5793(00)01813-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10922473">Van den Wyngaert et al. (2000)</a> obtained cDNAs encoding HDAC8. Sequence analysis predicted that the 377-amino acid HDAC8 protein contains the 9 conserved HDAC blocks that are presumably important for catalytic function (<a href="#4" class="mim-tip-reference" title="Hu, E., Chen, Z., Fredrickson, T., Zhu, Y., Kirkpatrick, R., Zhang, G.-F., Johanson, K., Sung, C.-M., Liu, R., Winkler, J. <strong>Cloning and characterization of a novel human class I histone deacetylase that functions as a transcription repressor.</strong> J. Biol. Chem. 275: 15254-15264, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10748112/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10748112</a>] [<a href="https://doi.org/10.1074/jbc.M908988199" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10748112">Hu et al., 2000</a>). <a href="#6" class="mim-tip-reference" title="Van den Wyngaert, I., de Vries, W., Kremer, A., Neefs, J.-M., Verhasselt, P., Luyten, W. H. M. L., Kass, S. U. <strong>Cloning and characterization of human histone deacetylase 8.</strong> FEBS Lett. 478: 77-83, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10922473/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10922473</a>] [<a href="https://doi.org/10.1016/s0014-5793(00)01813-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10922473">Van den Wyngaert et al. (2000)</a> noted that the approximately 30 amino acids at the N and C termini of HDAC8 are quite distinct from those of other HDACs. HDAC8 shares 54% sequence similarity with HDAC1 and HDAC2 and 39% similarity with HDAC3, making it a class I HDAC. Northern blot analysis detected HDAC8 transcripts of approximately 2.0 and 2.4 kb in all normal tissues tested, with strongest expression in brain, unlike other class I HDACs, and in cancer cell lines. Immunofluorescence analysis indicated a nuclear localization with possible exclusion from the nucleolus. By Western blot analysis, <a href="#4" class="mim-tip-reference" title="Hu, E., Chen, Z., Fredrickson, T., Zhu, Y., Kirkpatrick, R., Zhang, G.-F., Johanson, K., Sung, C.-M., Liu, R., Winkler, J. <strong>Cloning and characterization of a novel human class I histone deacetylase that functions as a transcription repressor.</strong> J. Biol. Chem. 275: 15254-15264, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10748112/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10748112</a>] [<a href="https://doi.org/10.1074/jbc.M908988199" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10748112">Hu et al. (2000)</a> confirmed the nuclear localization and showed that HDAC8 is expressed as a 49-kD protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10922473+10748112" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Buggy, J. J., Sideris, M. L., Mak, P., Lorimer, D. D., McIntosh, B., Clark, J. M. <strong>Cloning and characterization of a novel human histone deacetylase, HDAC8.</strong> Biochem. J. 350: 199-205, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10926844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10926844</a>]" pmid="10926844">Buggy et al. (2000)</a> also cloned and characterized HDAC8. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10926844" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#4" class="mim-tip-reference" title="Hu, E., Chen, Z., Fredrickson, T., Zhu, Y., Kirkpatrick, R., Zhang, G.-F., Johanson, K., Sung, C.-M., Liu, R., Winkler, J. <strong>Cloning and characterization of a novel human class I histone deacetylase that functions as a transcription repressor.</strong> J. Biol. Chem. 275: 15254-15264, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10748112/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10748112</a>] [<a href="https://doi.org/10.1074/jbc.M908988199" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10748112">Hu et al. (2000)</a> demonstrated that HDAC8 expresses deacetylation activity in nuclear extracts as well as with histones H3 and H4; this activity could be inhibited by Zn(2+), Cu(+), Fe(2+), trichostatin, and other inhibitors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10748112" 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>Mutation analysis by <a href="#1" class="mim-tip-reference" title="Buggy, J. J., Sideris, M. L., Mak, P., Lorimer, D. D., McIntosh, B., Clark, J. M. <strong>Cloning and characterization of a novel human histone deacetylase, HDAC8.</strong> Biochem. J. 350: 199-205, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10926844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10926844</a>]" pmid="10926844">Buggy et al. (2000)</a> showed that 2 adjacent histidine residues in the predicted active site, his142 and his143, are required for HDAC activity on H4 peptide substrates and core histones. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10926844" 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="Vannini, A., Volpari, C., Filocamo, G., Casavola, E. C., Brunetti, M., Renzoni, D., Chakravarty, P., Paolini, C., De Francesco, R., Gallinari, P., Steinkuhler, C., Di Marco, S. <strong>Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor.</strong> Proc. Nat. Acad. Sci. 101: 15064-15069, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15477595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15477595</a>] [<a href="https://doi.org/10.1073/pnas.0404603101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15477595">Vannini et al. (2004)</a> found that knockdown of HDAC8 by RNA interference inhibited the growth of human lung, colon, and cervical cancer cell lines. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15477595" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Deardorff, M. A., Bando, M., Nakato, R., Watrin, E., Itoh, T., Minamino, M., Saitoh, K., Komata, M., Katou, Y., Clark, D., Cole, K. E., De Baere, E., and 30 others. <strong>HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle.</strong> Nature 489: 313-317, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22885700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22885700</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22885700[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/nature11316" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22885700">Deardorff et al. (2012)</a> used RNAi-based screening of all known human histone deacetylases and sirtuins to identify HDAC8 as the vertebrate SMC3 (<a href="/entry/606062">606062</a>) deacetylase. Loss of HDAC8 activity using either HDAC8 RNAi or an HDAC8-specific inhibitor did not alter cell cycle progression, but clearly increased acetylated SMC3 in both soluble and chromatin fractions throughout the cell cycle. <a href="#2" class="mim-tip-reference" title="Deardorff, M. A., Bando, M., Nakato, R., Watrin, E., Itoh, T., Minamino, M., Saitoh, K., Komata, M., Katou, Y., Clark, D., Cole, K. E., De Baere, E., and 30 others. <strong>HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle.</strong> Nature 489: 313-317, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22885700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22885700</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22885700[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/nature11316" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22885700">Deardorff et al. (2012)</a> then showed that reduction in HDAC8 led to decreased occupancy of cohesin localization sites. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22885700" 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="#7" class="mim-tip-reference" title="Vannini, A., Volpari, C., Filocamo, G., Casavola, E. C., Brunetti, M., Renzoni, D., Chakravarty, P., Paolini, C., De Francesco, R., Gallinari, P., Steinkuhler, C., Di Marco, S. <strong>Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor.</strong> Proc. Nat. Acad. Sci. 101: 15064-15069, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15477595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15477595</a>] [<a href="https://doi.org/10.1073/pnas.0404603101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15477595">Vannini et al. (2004)</a> determined the crystal structure of HDAC8 complexed with an HDAC inhibitor to 2.5-angstrom resolution. HDAC8 forms a single compact alpha/beta domain composed of a central 8-stranded parallel beta sheet and 11 alpha helices. The twisted beta sheet is flanked by 5 helices on one side and 3 helices on the other. The active site has a narrow pocket to accommodate the acetylated lysine during the catalytic reaction, and at the bottom of this tunnel a pentacoordinated active site Zn(2+) ion is found. Below the active site there is a tube-like cavity filled with several water molecules that may shuttle the reaction product acetate. HDAC8 also has 2 K+ ion-binding sites, one of which interacts with key catalytic residues and is directly connected to the zinc-binding site. The K+ ions are required for the structural stability of HDAC8. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15477595" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By genomic sequence analysis, <a href="#6" class="mim-tip-reference" title="Van den Wyngaert, I., de Vries, W., Kremer, A., Neefs, J.-M., Verhasselt, P., Luyten, W. H. M. L., Kass, S. U. <strong>Cloning and characterization of human histone deacetylase 8.</strong> FEBS Lett. 478: 77-83, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10922473/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10922473</a>] [<a href="https://doi.org/10.1016/s0014-5793(00)01813-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10922473">Van den Wyngaert et al. (2000)</a> determined that the HDAC8 gene contains 11 exons and spans 243 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10922473" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using FISH, <a href="#6" class="mim-tip-reference" title="Van den Wyngaert, I., de Vries, W., Kremer, A., Neefs, J.-M., Verhasselt, P., Luyten, W. H. M. L., Kass, S. U. <strong>Cloning and characterization of human histone deacetylase 8.</strong> FEBS Lett. 478: 77-83, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10922473/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10922473</a>] [<a href="https://doi.org/10.1016/s0014-5793(00)01813-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10922473">Van den Wyngaert et al. (2000)</a> mapped the HDAC8 gene to Xq13, in the proximity of the XIST gene (<a href="/entry/314670">314670</a>). XIST is involved in the initiation of X chromosome inactivation, which correlates with histone deacetylation and DNA hypermethylation of the inactive X. The localization is also near Xq13 breakpoints associated with preleukemia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10922473" 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 radiation hybrid analysis, <a href="#1" class="mim-tip-reference" title="Buggy, J. J., Sideris, M. L., Mak, P., Lorimer, D. D., McIntosh, B., Clark, J. M. <strong>Cloning and characterization of a novel human histone deacetylase, HDAC8.</strong> Biochem. J. 350: 199-205, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10926844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10926844</a>]" pmid="10926844">Buggy et al. (2000)</a> mapped the HDAC8 gene to chromosome Xq21.2-q21.3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10926844" 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 affected members of a large family with a syndromic mental retardation disorder resembling Cornelia de Lange syndrome (CDLS5; <a href="/entry/300882">300882</a>), <a href="#3" class="mim-tip-reference" title="Harakalova, M., van den Boogaard, M.-J., Sinke, R., van Lieshout, S., van Tuil, M. C., Duran, K., Renkens, I., Terhal, P. A., de Kovel, C., Nijman, I. J., van Haelst, M., Knoers, N. V. A. M., van Haaften, G., Kloosterman, W., Hennekam, R. C. M., Cuppen, E., Ploos van Amstel, H. K. <strong>X-exome sequencing identifies a HDAC8 variant in a large pedigree with X-linked intellectual disability, truncal obesity, gynaecomastia, hypogonadism and unusual face.</strong> J. Med. Genet. 49: 539-543, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22889856/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22889856</a>] [<a href="https://doi.org/10.1136/jmedgenet-2012-100921" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22889856">Harakalova et al. (2012)</a> identified a splice site mutation in the HDAC8 gene (<a href="#0001">300269.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22889856" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Deardorff, M. A., Bando, M., Nakato, R., Watrin, E., Itoh, T., Minamino, M., Saitoh, K., Komata, M., Katou, Y., Clark, D., Cole, K. E., De Baere, E., and 30 others. <strong>HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle.</strong> Nature 489: 313-317, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22885700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22885700</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22885700[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/nature11316" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22885700">Deardorff et al. (2012)</a> screened 154 individuals with Cornelia de Lange syndrome negative for mutations in other implicated genes and identified 4 de novo missense mutations and 1 de novo nonsense mutation in HDAC8 (see, e.g., <a href="#0002">300269.0002</a>-<a href="#0005">300269.0005</a>). In addition, 1 familial mutation (<a href="#0006">300269.0006</a>) was identified in a boy, his mildly affected sister, and his unaffected mother; the mutant allele was inactivated in the mother's blood. This mutation occurred de novo in an unrelated girl. None of the mutations were found in 290 ethnically matched control chromosomes or in 629 individuals of the 1000 Genomes Project. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22885700" 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 whole-exome sequencing in a patient with Cornelia de Lange syndrome, <a href="#5" class="mim-tip-reference" title="Jezela-Stanek, A., Murcia, P. V., Jurkiewicz, D., Iwanicka-Pronicka, K., Jedrzejowska, M., Krajewska-Walasek, M., Ploski, R. <strong>Novel variant in HDAC8 gene resulting in the severe Cornelia de Lange phenotype.</strong> Clin. Dysmorph. 28: 126-130, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30921088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30921088</a>] [<a href="https://doi.org/10.1097/MCD.0000000000000277" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30921088">Jezela-Stanek et al. (2019)</a> identified a hemizygous missense mutation in the HDAC8 gene (c.938G-A, R313Q, NM_018486.2). The mutation was inherited from his unaffected mosaic mother. X-inactivation studies on the mother showed her to have random inactivation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30921088" 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 affected members of a large family with a syndromic disorder resembling Cornelia de Lange syndrome (CDLS5; <a href="/entry/300882">300882</a>), <a href="#3" class="mim-tip-reference" title="Harakalova, M., van den Boogaard, M.-J., Sinke, R., van Lieshout, S., van Tuil, M. C., Duran, K., Renkens, I., Terhal, P. A., de Kovel, C., Nijman, I. J., van Haelst, M., Knoers, N. V. A. M., van Haaften, G., Kloosterman, W., Hennekam, R. C. M., Cuppen, E., Ploos van Amstel, H. K. <strong>X-exome sequencing identifies a HDAC8 variant in a large pedigree with X-linked intellectual disability, truncal obesity, gynaecomastia, hypogonadism and unusual face.</strong> J. Med. Genet. 49: 539-543, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22889856/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22889856</a>] [<a href="https://doi.org/10.1136/jmedgenet-2012-100921" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22889856">Harakalova et al. (2012)</a> identified a G-to-A transition in the donor splice site of exon 2 of the HDAC8 gene (164+5G-A). Analysis of mRNA in lymphocytes derived from a male patient showed that the mutation resulted in a transcript lacking exon 2 and caused premature protein truncation (Ala38AspfsTer3) at the beginning of the histone deacetylase catalytic domain. However, a very small amount of normal HDAC8 transcript was also identified. The mutation, which was found by exome sequencing of the X chromosome, was not found in 96 Dutch male controls or in about 5,000 control exomes. Affected males had intellectual disability, gynecomastia, hypogonadism, and distinctive facial features. Female carriers showed milder features, including learning disabilities and facial dysmorphism; all female carriers showed skewed X inactivation, with the mutated allele inactivated. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22889856" 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 6-year-old female with features consistent with Cornelia de Lange syndrome (CDLS5; <a href="/entry/300882">300882</a>), <a href="#2" class="mim-tip-reference" title="Deardorff, M. A., Bando, M., Nakato, R., Watrin, E., Itoh, T., Minamino, M., Saitoh, K., Komata, M., Katou, Y., Clark, D., Cole, K. E., De Baere, E., and 30 others. <strong>HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle.</strong> Nature 489: 313-317, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22885700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22885700</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22885700[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/nature11316" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22885700">Deardorff et al. (2012)</a> identified a heterozygous de novo C-to-T transition at nucleotide 490 of the HDAC8 gene resulting in an arg-to-ter codon substitution at codon 164 (R164X). The patient had growth delays, absent speech, and characteristic facial features as well as asymmetric skull, limb length discrepancy, and dysplastic kidneys. This mutation was not seen in 290 ethnically matched control chromosomes or in 629 individuals of the 1000 Genomes Project. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22885700" 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 female patient with growth and facial features consistent with severe Cornelia de Lange (CDLS5; <a href="/entry/300882">300882</a>), <a href="#2" class="mim-tip-reference" title="Deardorff, M. A., Bando, M., Nakato, R., Watrin, E., Itoh, T., Minamino, M., Saitoh, K., Komata, M., Katou, Y., Clark, D., Cole, K. E., De Baere, E., and 30 others. <strong>HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle.</strong> Nature 489: 313-317, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22885700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22885700</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22885700[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/nature11316" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22885700">Deardorff et al. (2012)</a> identified a de novo heterozygous mutation in the HDAC8 gene, an A-to-G transition at nucleotide 539 resulting in a his-to-arg substitution at codon 180 (H180R). At 3 years of age the patient had moderate to severe cognitive impairment without limb abnormalities. She subsequently died in her teens. This mutation was not seen in 290 ethnically matched control chromosomes or in 629 individuals of the 1000 Genomes Project. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22885700" 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 CORNELIA DE LANGE SYNDROME 5</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs397515417 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397515417;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/rs397515417?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=rs397515417" 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=rs397515417" 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=RCV000032917 OR RCV000624803 OR RCV002264910" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032917, RCV000624803, RCV002264910" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032917...</a>
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<p>In a 1-year-old female with severe growth and cognitive delays and facial features of classic Cornelia de Lange syndrome (CDLS5; <a href="/entry/300882">300882</a>), <a href="#2" class="mim-tip-reference" title="Deardorff, M. A., Bando, M., Nakato, R., Watrin, E., Itoh, T., Minamino, M., Saitoh, K., Komata, M., Katou, Y., Clark, D., Cole, K. E., De Baere, E., and 30 others. <strong>HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle.</strong> Nature 489: 313-317, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22885700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22885700</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22885700[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/nature11316" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22885700">Deardorff et al. (2012)</a> identified a de novo C-to-T transition at nucleotide 932 in the HDAC8 gene, resulting in a thr-to-met substitution at codon 311 (T311M). The infant also had large fontanels, pulmonary stenosis, and unilateral hearing loss. She had no limb anomalies. This mutation was not seen in 290 ethnically matched control chromosomes or in 629 individuals of the 1000 Genomes Project. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22885700" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<span class="mim-font">
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<strong>.0005 CORNELIA DE LANGE SYNDROME 5</strong>
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HDAC8, GLY320ARG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs398122909 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs398122909;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=rs398122909" 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=rs398122909" 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=RCV000032918 OR RCV000211117 OR RCV001030829 OR RCV001588839 OR RCV002381278" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032918, RCV000211117, RCV001030829, RCV001588839, RCV002381278" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032918...</a>
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<span class="mim-text-font">
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<p>In a 5-year-boy boy with severe cognitive and growth delays and facial features consistent with Cornelia de Lange syndrome (CDLS5; <a href="/entry/300882">300882</a>), <a href="#2" class="mim-tip-reference" title="Deardorff, M. A., Bando, M., Nakato, R., Watrin, E., Itoh, T., Minamino, M., Saitoh, K., Komata, M., Katou, Y., Clark, D., Cole, K. E., De Baere, E., and 30 others. <strong>HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle.</strong> Nature 489: 313-317, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22885700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22885700</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22885700[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/nature11316" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22885700">Deardorff et al. (2012)</a> identified a hemizygous de novo G-to-A transition at nucleotide 958 of the HDAC8 gene, resulting in a gly-to-arg substitution at codon 320 (G320R). Additionally the boy had large fontanels, atrial septum aneurysm, bilateral hearing loss, and a happy personality. This mutation was not seen in 290 ethnically matched control chromosomes or in 629 individuals of the 1000 Genomes Project. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22885700" 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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<h4>
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<span class="mim-font">
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<strong>.0006 CORNELIA DE LANGE SYNDROME 5</strong>
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HDAC8, HIS334ARG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs397515418 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397515418;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=rs397515418" 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=rs397515418" 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=RCV000032919" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032919" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032919</a>
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<span class="mim-text-font">
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<p>In a 7-year-old heterozygous female with severe cognitive and growth delays and facial features suggestive of Cornelia de Lange syndrome (CDLS5; <a href="/entry/300882">300882</a>), <a href="#2" class="mim-tip-reference" title="Deardorff, M. A., Bando, M., Nakato, R., Watrin, E., Itoh, T., Minamino, M., Saitoh, K., Komata, M., Katou, Y., Clark, D., Cole, K. E., De Baere, E., and 30 others. <strong>HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle.</strong> Nature 489: 313-317, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22885700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22885700</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22885700[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/nature11316" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22885700">Deardorff et al. (2012)</a> identified an A-to-G transition at nucleotide 1001 of the HDAC8 gene, resulting in a his-to-arg substitution at codon 334 (H334R). The patient also had delayed fontanel closure, limb length difference but no deficiencies, and a happy and introverted demeanor. This mutation was heterozygous and de novo in this female, but was identified in a second family. The proband was a 13-year-old hemizygous male with severe cognitive and growth delay and facial features consistent with Cornelia de Lange syndrome. He had an 8-year-old heterozygous affected sister with mild cognitive and growth delays and mildly affected facial features. The unaffected mother was heterozygous with completely skewed X inactivation. This mutation was not seen in 290 ethnically matched control chromosomes or in 629 individuals of the 1000 Genomes Project. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22885700" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="references"class="mim-anchor"></a>
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<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>REFERENCES</strong>
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<a id="Buggy2000" class="mim-anchor"></a>
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Buggy, J. J., Sideris, M. L., Mak, P., Lorimer, D. D., McIntosh, B., Clark, J. M.
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<strong>Cloning and characterization of a novel human histone deacetylase, HDAC8.</strong>
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Biochem. J. 350: 199-205, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10926844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10926844</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10926844" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="Deardorff2012" class="mim-anchor"></a>
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Deardorff, M. A., Bando, M., Nakato, R., Watrin, E., Itoh, T., Minamino, M., Saitoh, K., Komata, M., Katou, Y., Clark, D., Cole, K. E., De Baere, E., and 30 others.
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<strong>HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle.</strong>
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Nature 489: 313-317, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22885700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22885700</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22885700[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=22885700" 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/nature11316" target="_blank">Full Text</a>]
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<a id="Harakalova2012" class="mim-anchor"></a>
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Harakalova, M., van den Boogaard, M.-J., Sinke, R., van Lieshout, S., van Tuil, M. C., Duran, K., Renkens, I., Terhal, P. A., de Kovel, C., Nijman, I. J., van Haelst, M., Knoers, N. V. A. M., van Haaften, G., Kloosterman, W., Hennekam, R. C. M., Cuppen, E., Ploos van Amstel, H. K.
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<strong>X-exome sequencing identifies a HDAC8 variant in a large pedigree with X-linked intellectual disability, truncal obesity, gynaecomastia, hypogonadism and unusual face.</strong>
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J. Med. Genet. 49: 539-543, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22889856/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22889856</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22889856" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1136/jmedgenet-2012-100921" target="_blank">Full Text</a>]
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<a id="Hu2000" class="mim-anchor"></a>
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Hu, E., Chen, Z., Fredrickson, T., Zhu, Y., Kirkpatrick, R., Zhang, G.-F., Johanson, K., Sung, C.-M., Liu, R., Winkler, J.
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<strong>Cloning and characterization of a novel human class I histone deacetylase that functions as a transcription repressor.</strong>
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J. Biol. Chem. 275: 15254-15264, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10748112/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10748112</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10748112" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.M908988199" target="_blank">Full Text</a>]
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<a id="Jezela-Stanek2019" class="mim-anchor"></a>
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Jezela-Stanek, A., Murcia, P. V., Jurkiewicz, D., Iwanicka-Pronicka, K., Jedrzejowska, M., Krajewska-Walasek, M., Ploski, R.
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<strong>Novel variant in HDAC8 gene resulting in the severe Cornelia de Lange phenotype.</strong>
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Clin. Dysmorph. 28: 126-130, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30921088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30921088</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30921088" 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/10.1097/MCD.0000000000000277" target="_blank">Full Text</a>]
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Van den Wyngaert, I., de Vries, W., Kremer, A., Neefs, J.-M., Verhasselt, P., Luyten, W. H. M. L., Kass, S. U.
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<strong>Cloning and characterization of human histone deacetylase 8.</strong>
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FEBS Lett. 478: 77-83, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10922473/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10922473</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10922473" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0014-5793(00)01813-5" 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="7" class="mim-anchor"></a>
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<a id="Vannini2004" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Vannini, A., Volpari, C., Filocamo, G., Casavola, E. C., Brunetti, M., Renzoni, D., Chakravarty, P., Paolini, C., De Francesco, R., Gallinari, P., Steinkuhler, C., Di Marco, S.
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<strong>Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor.</strong>
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Proc. Nat. Acad. Sci. 101: 15064-15069, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15477595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15477595</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15477595" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.0404603101" target="_blank">Full Text</a>]
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Sonja A. Rasmussen - updated : 08/05/2022
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 08/04/2016<br>Matthew B. Gross - updated : 11/13/2015<br>Ada Hamosh - updated : 10/10/2012<br>Cassandra L. Kniffin - updated : 10/3/2012<br>Patricia A. Hartz - updated : 11/12/2004<br>Paul J. Converse - updated : 3/1/2002
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<a id="creationDate" 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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Creation Date:
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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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Paul J. Converse : 10/3/2000
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</span>
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</div>
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 08/05/2022
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<span class="mim-text-font">
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carol : 06/21/2018<br>carol : 08/08/2016<br>ckniffin : 08/04/2016<br>mgross : 11/13/2015<br>carol : 11/10/2015<br>alopez : 10/23/2012<br>terry : 10/10/2012<br>carol : 10/3/2012<br>ckniffin : 10/3/2012<br>mgross : 9/19/2008<br>mgross : 11/12/2004<br>mgross : 3/1/2002<br>mgross : 10/5/2000<br>mgross : 10/3/2000
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<div class="container visible-print-block">
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 300269
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</span>
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</h3>
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<div>
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<h3>
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<span class="mim-font">
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HISTONE DEACETYLASE 8; HDAC8
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</span>
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</h3>
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</div>
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<div>
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<br />
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: HDAC8</em></strong>
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</span>
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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: Xq13.1
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Genomic coordinates <span class="small">(GRCh38)</span> : X:72,329,516-72,572,843 </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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<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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</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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Xq13.1
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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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Cornelia de Lange syndrome 5
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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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300882
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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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X-linked dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</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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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Reversible acetylation of N-terminal histone tails is a key determinant of gene expression, with hyperacetylation resulting in transcriptional activation, and deacetylation correlating with transcriptional silencing. The level of histone acetylation is determined by the opposing activities of histone acetyltransferases (see HAT1, 603053) and deacetylases (see HDAC1, 601241). HDACs are divided into 2 classes: class I, which contains HDACs similar to HDAC1, and class II, which contains HDACs whose C termini share homology with yeast Hda1 (e.g., HDAC4, 605314). HDAC8 is a class I HDAC (Van den Wyngaert et al., 2000). </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 searching an EST database for sequences similar to HDAC1, HDAC2, and HDAC3, followed by 5-prime and 3-prime RACE, Hu et al. (2000) and Van den Wyngaert et al. (2000) obtained cDNAs encoding HDAC8. Sequence analysis predicted that the 377-amino acid HDAC8 protein contains the 9 conserved HDAC blocks that are presumably important for catalytic function (Hu et al., 2000). Van den Wyngaert et al. (2000) noted that the approximately 30 amino acids at the N and C termini of HDAC8 are quite distinct from those of other HDACs. HDAC8 shares 54% sequence similarity with HDAC1 and HDAC2 and 39% similarity with HDAC3, making it a class I HDAC. Northern blot analysis detected HDAC8 transcripts of approximately 2.0 and 2.4 kb in all normal tissues tested, with strongest expression in brain, unlike other class I HDACs, and in cancer cell lines. Immunofluorescence analysis indicated a nuclear localization with possible exclusion from the nucleolus. By Western blot analysis, Hu et al. (2000) confirmed the nuclear localization and showed that HDAC8 is expressed as a 49-kD protein. </p><p>Buggy et al. (2000) also cloned and characterized HDAC8. </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>Hu et al. (2000) demonstrated that HDAC8 expresses deacetylation activity in nuclear extracts as well as with histones H3 and H4; this activity could be inhibited by Zn(2+), Cu(+), Fe(2+), trichostatin, and other inhibitors. </p><p>Mutation analysis by Buggy et al. (2000) showed that 2 adjacent histidine residues in the predicted active site, his142 and his143, are required for HDAC activity on H4 peptide substrates and core histones. </p><p>Vannini et al. (2004) found that knockdown of HDAC8 by RNA interference inhibited the growth of human lung, colon, and cervical cancer cell lines. </p><p>Deardorff et al. (2012) used RNAi-based screening of all known human histone deacetylases and sirtuins to identify HDAC8 as the vertebrate SMC3 (606062) deacetylase. Loss of HDAC8 activity using either HDAC8 RNAi or an HDAC8-specific inhibitor did not alter cell cycle progression, but clearly increased acetylated SMC3 in both soluble and chromatin fractions throughout the cell cycle. Deardorff et al. (2012) then showed that reduction in HDAC8 led to decreased occupancy of cohesin localization sites. </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>Biochemical Features</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>Vannini et al. (2004) determined the crystal structure of HDAC8 complexed with an HDAC inhibitor to 2.5-angstrom resolution. HDAC8 forms a single compact alpha/beta domain composed of a central 8-stranded parallel beta sheet and 11 alpha helices. The twisted beta sheet is flanked by 5 helices on one side and 3 helices on the other. The active site has a narrow pocket to accommodate the acetylated lysine during the catalytic reaction, and at the bottom of this tunnel a pentacoordinated active site Zn(2+) ion is found. Below the active site there is a tube-like cavity filled with several water molecules that may shuttle the reaction product acetate. HDAC8 also has 2 K+ ion-binding sites, one of which interacts with key catalytic residues and is directly connected to the zinc-binding site. The K+ ions are required for the structural stability of HDAC8. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Gene Structure</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
|
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<p>By genomic sequence analysis, Van den Wyngaert et al. (2000) determined that the HDAC8 gene contains 11 exons and spans 243 kb. </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">
|
|
<p>Using FISH, Van den Wyngaert et al. (2000) mapped the HDAC8 gene to Xq13, in the proximity of the XIST gene (314670). XIST is involved in the initiation of X chromosome inactivation, which correlates with histone deacetylation and DNA hypermethylation of the inactive X. The localization is also near Xq13 breakpoints associated with preleukemia. </p><p>By radiation hybrid analysis, Buggy et al. (2000) mapped the HDAC8 gene to chromosome Xq21.2-q21.3. </p>
|
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Molecular Genetics</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In affected members of a large family with a syndromic mental retardation disorder resembling Cornelia de Lange syndrome (CDLS5; 300882), Harakalova et al. (2012) identified a splice site mutation in the HDAC8 gene (300269.0001). </p><p>Deardorff et al. (2012) screened 154 individuals with Cornelia de Lange syndrome negative for mutations in other implicated genes and identified 4 de novo missense mutations and 1 de novo nonsense mutation in HDAC8 (see, e.g., 300269.0002-300269.0005). In addition, 1 familial mutation (300269.0006) was identified in a boy, his mildly affected sister, and his unaffected mother; the mutant allele was inactivated in the mother's blood. This mutation occurred de novo in an unrelated girl. None of the mutations were found in 290 ethnically matched control chromosomes or in 629 individuals of the 1000 Genomes Project. </p><p>By whole-exome sequencing in a patient with Cornelia de Lange syndrome, Jezela-Stanek et al. (2019) identified a hemizygous missense mutation in the HDAC8 gene (c.938G-A, R313Q, NM_018486.2). The mutation was inherited from his unaffected mosaic mother. X-inactivation studies on the mother showed her to have random inactivation. </p>
|
|
</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>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>6 Selected Examples):</strong>
|
|
</span>
|
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</h4>
|
|
<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 CORNELIA DE LANGE SYNDROME 5</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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HDAC8, IVS1DS, G-A, +5
|
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<br />
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SNP: rs398122888,
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ClinVar: RCV000030813, RCV003415747
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In affected members of a large family with a syndromic disorder resembling Cornelia de Lange syndrome (CDLS5; 300882), Harakalova et al. (2012) identified a G-to-A transition in the donor splice site of exon 2 of the HDAC8 gene (164+5G-A). Analysis of mRNA in lymphocytes derived from a male patient showed that the mutation resulted in a transcript lacking exon 2 and caused premature protein truncation (Ala38AspfsTer3) at the beginning of the histone deacetylase catalytic domain. However, a very small amount of normal HDAC8 transcript was also identified. The mutation, which was found by exome sequencing of the X chromosome, was not found in 96 Dutch male controls or in about 5,000 control exomes. Affected males had intellectual disability, gynecomastia, hypogonadism, and distinctive facial features. Female carriers showed milder features, including learning disabilities and facial dysmorphism; all female carriers showed skewed X inactivation, with the mutated allele inactivated. </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 CORNELIA DE LANGE SYNDROME 5</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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HDAC8, ARG164TER
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<br />
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SNP: rs397515415,
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ClinVar: RCV000032915, RCV000480167
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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 6-year-old female with features consistent with Cornelia de Lange syndrome (CDLS5; 300882), Deardorff et al. (2012) identified a heterozygous de novo C-to-T transition at nucleotide 490 of the HDAC8 gene resulting in an arg-to-ter codon substitution at codon 164 (R164X). The patient had growth delays, absent speech, and characteristic facial features as well as asymmetric skull, limb length discrepancy, and dysplastic kidneys. This mutation was not seen in 290 ethnically matched control chromosomes or in 629 individuals of the 1000 Genomes Project. </p>
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<span class="mim-font">
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<strong>.0003 CORNELIA DE LANGE SYNDROME 5</strong>
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HDAC8, HIS180ARG
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<br />
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SNP: rs397515416,
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ClinVar: RCV000032916
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<p>In a female patient with growth and facial features consistent with severe Cornelia de Lange (CDLS5; 300882), Deardorff et al. (2012) identified a de novo heterozygous mutation in the HDAC8 gene, an A-to-G transition at nucleotide 539 resulting in a his-to-arg substitution at codon 180 (H180R). At 3 years of age the patient had moderate to severe cognitive impairment without limb abnormalities. She subsequently died in her teens. This mutation was not seen in 290 ethnically matched control chromosomes or in 629 individuals of the 1000 Genomes Project. </p>
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<span class="mim-font">
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<strong>.0004 CORNELIA DE LANGE SYNDROME 5</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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HDAC8, THR311MET
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<br />
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SNP: rs397515417,
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gnomAD: rs397515417,
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ClinVar: RCV000032917, RCV000624803, RCV002264910
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</span>
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<p>In a 1-year-old female with severe growth and cognitive delays and facial features of classic Cornelia de Lange syndrome (CDLS5; 300882), Deardorff et al. (2012) identified a de novo C-to-T transition at nucleotide 932 in the HDAC8 gene, resulting in a thr-to-met substitution at codon 311 (T311M). The infant also had large fontanels, pulmonary stenosis, and unilateral hearing loss. She had no limb anomalies. This mutation was not seen in 290 ethnically matched control chromosomes or in 629 individuals of the 1000 Genomes Project. </p>
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</span>
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</div>
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<h4>
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<span class="mim-font">
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<strong>.0005 CORNELIA DE LANGE SYNDROME 5</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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HDAC8, GLY320ARG
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<br />
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SNP: rs398122909,
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ClinVar: RCV000032918, RCV000211117, RCV001030829, RCV001588839, RCV002381278
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</span>
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</div>
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<span class="mim-text-font">
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<p>In a 5-year-boy boy with severe cognitive and growth delays and facial features consistent with Cornelia de Lange syndrome (CDLS5; 300882), Deardorff et al. (2012) identified a hemizygous de novo G-to-A transition at nucleotide 958 of the HDAC8 gene, resulting in a gly-to-arg substitution at codon 320 (G320R). Additionally the boy had large fontanels, atrial septum aneurysm, bilateral hearing loss, and a happy personality. This mutation was not seen in 290 ethnically matched control chromosomes or in 629 individuals of the 1000 Genomes Project. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0006 CORNELIA DE LANGE SYNDROME 5</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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HDAC8, HIS334ARG
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<br />
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SNP: rs397515418,
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ClinVar: RCV000032919
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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 heterozygous female with severe cognitive and growth delays and facial features suggestive of Cornelia de Lange syndrome (CDLS5; 300882), Deardorff et al. (2012) identified an A-to-G transition at nucleotide 1001 of the HDAC8 gene, resulting in a his-to-arg substitution at codon 334 (H334R). The patient also had delayed fontanel closure, limb length difference but no deficiencies, and a happy and introverted demeanor. This mutation was heterozygous and de novo in this female, but was identified in a second family. The proband was a 13-year-old hemizygous male with severe cognitive and growth delay and facial features consistent with Cornelia de Lange syndrome. He had an 8-year-old heterozygous affected sister with mild cognitive and growth delays and mildly affected facial features. The unaffected mother was heterozygous with completely skewed X inactivation. This mutation was not seen in 290 ethnically matched control chromosomes or in 629 individuals of the 1000 Genomes Project. </p>
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</span>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Buggy, J. J., Sideris, M. L., Mak, P., Lorimer, D. D., McIntosh, B., Clark, J. M.
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<strong>Cloning and characterization of a novel human histone deacetylase, HDAC8.</strong>
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Biochem. J. 350: 199-205, 2000.
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[PubMed: 10926844]
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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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Deardorff, M. A., Bando, M., Nakato, R., Watrin, E., Itoh, T., Minamino, M., Saitoh, K., Komata, M., Katou, Y., Clark, D., Cole, K. E., De Baere, E., and 30 others.
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|
<strong>HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle.</strong>
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Nature 489: 313-317, 2012.
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[PubMed: 22885700]
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[Full Text: https://doi.org/10.1038/nature11316]
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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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Harakalova, M., van den Boogaard, M.-J., Sinke, R., van Lieshout, S., van Tuil, M. C., Duran, K., Renkens, I., Terhal, P. A., de Kovel, C., Nijman, I. J., van Haelst, M., Knoers, N. V. A. M., van Haaften, G., Kloosterman, W., Hennekam, R. C. M., Cuppen, E., Ploos van Amstel, H. K.
|
|
<strong>X-exome sequencing identifies a HDAC8 variant in a large pedigree with X-linked intellectual disability, truncal obesity, gynaecomastia, hypogonadism and unusual face.</strong>
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|
J. Med. Genet. 49: 539-543, 2012.
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[PubMed: 22889856]
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[Full Text: https://doi.org/10.1136/jmedgenet-2012-100921]
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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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Hu, E., Chen, Z., Fredrickson, T., Zhu, Y., Kirkpatrick, R., Zhang, G.-F., Johanson, K., Sung, C.-M., Liu, R., Winkler, J.
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|
<strong>Cloning and characterization of a novel human class I histone deacetylase that functions as a transcription repressor.</strong>
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J. Biol. Chem. 275: 15254-15264, 2000.
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[PubMed: 10748112]
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[Full Text: https://doi.org/10.1074/jbc.M908988199]
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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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Jezela-Stanek, A., Murcia, P. V., Jurkiewicz, D., Iwanicka-Pronicka, K., Jedrzejowska, M., Krajewska-Walasek, M., Ploski, R.
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|
<strong>Novel variant in HDAC8 gene resulting in the severe Cornelia de Lange phenotype.</strong>
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Clin. Dysmorph. 28: 126-130, 2019.
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[PubMed: 30921088]
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[Full Text: https://doi.org/10.1097/MCD.0000000000000277]
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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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Van den Wyngaert, I., de Vries, W., Kremer, A., Neefs, J.-M., Verhasselt, P., Luyten, W. H. M. L., Kass, S. U.
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<strong>Cloning and characterization of human histone deacetylase 8.</strong>
|
|
FEBS Lett. 478: 77-83, 2000.
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[PubMed: 10922473]
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[Full Text: https://doi.org/10.1016/s0014-5793(00)01813-5]
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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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Vannini, A., Volpari, C., Filocamo, G., Casavola, E. C., Brunetti, M., Renzoni, D., Chakravarty, P., Paolini, C., De Francesco, R., Gallinari, P., Steinkuhler, C., Di Marco, S.
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<strong>Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor.</strong>
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Proc. Nat. Acad. Sci. 101: 15064-15069, 2004.
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[PubMed: 15477595]
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[Full Text: https://doi.org/10.1073/pnas.0404603101]
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</p>
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</li>
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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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Sonja A. Rasmussen - updated : 08/05/2022<br>Cassandra L. Kniffin - updated : 08/04/2016<br>Matthew B. Gross - updated : 11/13/2015<br>Ada Hamosh - updated : 10/10/2012<br>Cassandra L. Kniffin - updated : 10/3/2012<br>Patricia A. Hartz - updated : 11/12/2004<br>Paul J. Converse - updated : 3/1/2002
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<span class="mim-text-font">
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Paul J. Converse : 10/3/2000
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carol : 08/05/2022<br>carol : 06/21/2018<br>carol : 08/08/2016<br>ckniffin : 08/04/2016<br>mgross : 11/13/2015<br>carol : 11/10/2015<br>alopez : 10/23/2012<br>terry : 10/10/2012<br>carol : 10/3/2012<br>ckniffin : 10/3/2012<br>mgross : 9/19/2008<br>mgross : 11/12/2004<br>mgross : 3/1/2002<br>mgross : 10/5/2000<br>mgross : 10/3/2000
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