3411 lines
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Entry
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- *603277 - CHROMODOMAIN HELICASE DNA-BINDING PROTEIN 4; CHD4
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- OMIM
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<p>
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<span class="h4">*603277</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<a href="#geneFamily">Gene Family</a>
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<a href="#geneFunction">Gene Function</a>
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<a href="#mapping">Mapping</a>
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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/603277">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div 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 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=ENSG00000111642;t=ENST00000544040" 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=1108" 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=603277" 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 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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</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=ENSG00000111642;t=ENST00000544040" 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_001273,NM_001297553,NM_001363606" 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_001273" 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=603277" 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=04472&isoform_id=04472_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/CHD4" 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/1107696,24047226,51599156,116283480,116283563,119609183,119609184,119609185,193785938,311033360,662033891,1391723816" 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/Q14839" 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=1108" 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=ENSG00000111642;t=ENST00000544040" 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=CHD4" 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=CHD4" 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+1108" 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/CHD4" 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:1108" 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/1108" 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=chr12&hgg_gene=ENST00000644480.2&hgg_start=6570082&hgg_end=6607379&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:1919" 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:1919" 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=603277[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 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=603277[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/CHD4/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/ENSG00000111642" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=CHD4" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=CHD4" 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=CHD4" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=CHD4&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/PA26455" 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:1919" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0262519.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1344380" 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/CHD4#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:1344380" 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/1108/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=1108" 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="mim#WormbaseGeneFold" id="mimWormbaseGeneToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes."><span id="mimWormbaseGeneToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Wormbase Gene</div>
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<div id="mimWormbaseGeneFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00000482;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00000482 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00002637;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00002637 </a></div>
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</div>
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<div><a href="https://zfin.org/ZDB-GENE-030131-4532" 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:1108" 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=CHD4&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 1332510002<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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603277
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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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CHROMODOMAIN HELICASE DNA-BINDING PROTEIN 4; CHD4
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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Mi2-BETA
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=CHD4" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">CHD4</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/12/60?start=-3&limit=10&highlight=60">12p13.31</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr12:6570082-6607379&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'})">12:6,570,082-6,607,379</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>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
|
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<tr class="active">
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<th>
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|
Location
|
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
|
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</th>
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<th>
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Phenotype <br /> mapping key
|
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
|
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<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/12/60?start=-3&limit=10&highlight=60">
|
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12p13.31
|
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</a>
|
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</span>
|
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</td>
|
|
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|
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<td>
|
|
<span class="mim-font">
|
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Sifrim-Hitz-Weiss syndrome
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
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<a href="/entry/617159"> 617159 </a>
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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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/603277" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/603277" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
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<p>The CHD4 gene encodes a chromodomain-containing protein that catalyzes ATP-dependent chromatin remodeling as a core component of the nucleosome remodeling and histone deacetylase (NURD) repressor complex, which is involved in epigenetic regulation of gene transcription, DNA repair, and cell cycle progression (summary by <a href="#7" class="mim-tip-reference" title="Sifrim, A., Hitz, M.-P., Wilsdon, A., Breckpot, J., Al Turki, S. H., Thienpont, B., McRae, J., Fitzgerald, T. W., Singh, T., Swaminathan, G. J., Prigmore, E., Rajan, D., and 63 others. <strong>Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing.</strong> Nature Genet. 48: 1060-1065, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27479907/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27479907</a>] [<a href="https://doi.org/10.1038/ng.3627" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27479907">Sifrim et al., 2016</a> and <a href="#10" class="mim-tip-reference" title="Weiss, K., Terhal, P. A., Cohen, L., Bruccoleri, M., Irving, M., Martinez, A. F., Rosenfeld, J. A., Machol, K., Yang, Y., Liu, P., Walkiewicz, M., Beuten, J., and 16 others. <strong>De novo mutations in CHD4, an ATP-dependent chromatin remodeler gene, cause an intellectual disability syndrome with distinctive dysmorphisms.</strong> Am. J. Hum. Genet. 99: 934-941, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27616479/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27616479</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27616479[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.08.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27616479">Weiss et al., 2016</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=27479907+27616479" 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>Approximately 20% of patients with dermatomyositis develop antibodies against nuclear antigens that are termed Mi2. Sera containing anti-Mi2 antibodies precipitate several proteins, with 1 of the most abundant migrating as a 220- to 260-kD polypeptide on SDS-polyacrylamide gels. By immunoscreening a HeLa cell cDNA expression library with sera from a patient with dermatomyositis, <a href="#4" class="mim-tip-reference" title="Seelig, H. P., Moosbrugger, I., Ehrfeld, H., Fink, T., Renz, M., Genth, E. <strong>The major dermatomyositis-specific Mi-2 autoantigen is a presumed helicase involved in transcriptional activation.</strong> Arthritis Rheum. 38: 1389-1399, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7575689/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7575689</a>] [<a href="https://doi.org/10.1002/art.1780381006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7575689">Seelig et al. (1995)</a> isolated a full-length cDNA encoding CHD4, which they called Mi2-beta. Northern blot analysis of Hep-2 cell RNA detected an approximately 6.8-kb Mi2-beta transcript. The deduced 1,912-amino acid protein has a calculated molecular mass of 218 kD. Native Mi2-beta from Hep-2 cells has a molecular mass of 235 kD by SDS-PAGE. Searches of sequence databases indicated that Mi2-beta belongs to the SNF2/RAD54 family of nuclear helicases. The central portion of Mi2-beta contains the 7 motifs, including a DEAD/H box, that are characteristic of helicases. Mi2-beta also contains a putative chromatin-binding region and multiple potential nuclear targeting signals, N-glycosylation sites, N-myristoylation sites, and phosphorylation sites. Immunofluorescence studies localized the Mi2-beta protein to the nucleus. The authors concluded that Mi2-beta is a major antigen recognized by anti-Mi2 sera from patients with dermatomyositis. Studies with sera from dermatomyositis, systemic lupus erythematosus (<a href="/entry/152700">152700</a>), and rheumatoid arthritis (<a href="/entry/180300">180300</a>) patients showed that anti-Mi2-beta antibodies are predominantly found in dermatomyositis patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7575689" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Seelig, H. P., Renz, M., Targoff, I. N., Ge, Q., Frank, M. B. <strong>Two forms of the major antigenic protein of the dermatomyositis-specific Mi-2 autoantigen. (Letter)</strong> Arthritis Rheum. 39: 1769-1771, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8843877/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8843877</a>] [<a href="https://doi.org/10.1002/art.1780391029" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8843877">Seelig et al. (1996)</a> noted that the Mi2-alpha (CHD3; <a href="/entry/602120">602120</a>) and Mi2-beta proteins react with most or all dermatomyositis patient anti-Mi2 sera. While these proteins are distinct, they have stretches of identical sequences that could result in shared epitopes. The authors stated that Mi2-alpha and Mi2-beta contain a PHD motif, which is a zinc finger-like motif with a cys4-his-cys3 pattern and which is thought to be a DNA- or RNA-binding domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8843877" 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>See CHD1 (<a href="/entry/602118">602118</a>) for a description of this gene family.</p>
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<p><a href="#11" class="mim-tip-reference" title="Zhang, Y., LeRoy, G., Seelig, H.-P., Lane, W. S., Reinberg, D. <strong>The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities.</strong> Cell 95: 279-289, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9790534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9790534</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81758-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9790534">Zhang et al. (1998)</a> reported the isolation of a protein complex that contains both histone deacetylation and ATP-dependent nucleosome remodeling activities. The complex contained the histone deacetylases HDAC1/2, histone-binding proteins, the dermatomyositis-specific autoantigen Mi2-beta, a polypeptide related to the metastasis-associated protein-1, and a novel polypeptide of 32 kD. Patients with dermatomyositis have a high rate of malignancy. The finding that Mi2-beta exists in a complex containing histone deacetylase and nucleosome remodeling activities suggests a role for chromatin reorganization in cancer metastasis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9790534" 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="#12" class="mim-tip-reference" title="Zhang, Y., Ng, H.-H., Erdjument-Bromage, H., Tempst, P., Bird, A., Reinberg, D. <strong>Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation.</strong> Genes Dev. 13: 1924-1935, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10444591/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10444591</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10444591[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/10.1101/gad.13.15.1924" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10444591">Zhang et al. (1999)</a> showed that MTA2 (MTA1L1; <a href="/entry/603947">603947</a>) and the 32-kD MBD3 (<a href="/entry/603573">603573</a>) protein are subunits of the NURD (nucleosome remodeling and histone deacetylase) complex (see MTA1; <a href="/entry/603526">603526</a>). Immunoprecipitation analysis showed that MBD3 interacts with HDAC1 (<a href="/entry/601241">601241</a>), RBBP4 (<a href="/entry/602923">602923</a>), and RBBP7 (<a href="/entry/300825">300825</a>), but not with MI2, suggesting that MBD3 is embedded within the NURD complex. The authors found that MTA2 directs the assembly of an active histone deacetylase complex and that the association of MTA2 with the complex requires MBD3. Gel mobility shift analysis determined that both NURD and MBD3 are unable to bind to methylated DNA in the absence of MBD2 (<a href="/entry/603547">603547</a>). <a href="#12" class="mim-tip-reference" title="Zhang, Y., Ng, H.-H., Erdjument-Bromage, H., Tempst, P., Bird, A., Reinberg, D. <strong>Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation.</strong> Genes Dev. 13: 1924-1935, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10444591/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10444591</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10444591[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/10.1101/gad.13.15.1924" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10444591">Zhang et al. (1999)</a> proposed that NURD is involved in the transcriptional repression of methylated DNA. <a href="#9" class="mim-tip-reference" title="Wade, P. A., Gegonne, A., Jones, P. L., Ballestar, E., Aubry, F., Wolffe, A. P. <strong>Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation.</strong> Nature Genet. 23: 62-66, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10471500/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10471500</a>] [<a href="https://doi.org/10.1038/12664" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10471500">Wade et al. (1999)</a> also identified MTA1, MTA1L, and MBD3 as components of the NURD complex, which they referred to as the MI2 complex. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10471500+10444591" 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 immunoprecipitation analysis, <a href="#6" class="mim-tip-reference" title="Shimono, K., Shimono, Y., Shimokata, K., Ishiguro, N., Takahashi, M. <strong>Microspherule protein 1, Mi-2-beta, and RET finger protein associate in the nucleolus and up-regulate ribosomal gene transcription.</strong> J. Biol. Chem. 280: 39436-39447, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16186106/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16186106</a>] [<a href="https://doi.org/10.1074/jbc.M507356200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16186106">Shimono et al. (2005)</a> found that MCRS1 (<a href="/entry/609504">609504</a>) interacted with MI2-beta, RFP (TRIM27; <a href="/entry/602165">602165</a>), and UBF (UBTF; <a href="/entry/600673">600673</a>). Yeast 2-hybrid screening showed that the central region of MCRS1 interacted with the ATPase/helicase region of MI2-beta and the coiled-coil region of RFP. Confocal microscopy demonstrated colocalization of MCRS1, MI2-beta, RFP, and UBF in nucleoli. Chromatin immunoprecipitation assays showed that MCRS1, MI2-beta, and RFP associated with rDNA and were involved in transactivation of ribosomal gene transcription, which could be downregulated by small interfering RNA-mediated downregulation of MCRS1, MI2-beta, and RFP. <a href="#6" class="mim-tip-reference" title="Shimono, K., Shimono, Y., Shimokata, K., Ishiguro, N., Takahashi, M. <strong>Microspherule protein 1, Mi-2-beta, and RET finger protein associate in the nucleolus and up-regulate ribosomal gene transcription.</strong> J. Biol. Chem. 280: 39436-39447, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16186106/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16186106</a>] [<a href="https://doi.org/10.1074/jbc.M507356200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16186106">Shimono et al. (2005)</a> concluded that MI2-beta and RFP, which are involved in transcriptional repression in the nucleus, associate with MCRS1 in the nucleolus and are involved in activation of rRNA transcription. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16186106" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Ostapcuk, V., Mohn, F., Carl, S. H., Basters, A., Hess, D., Iesmantavicius, V., Lampersberger, L., Flemr, M., Pandey, A., Thoma, N. H., Betschinger, J., Buhler, M. <strong>Activity-dependent neuroprotective protein recruits HP1 and CHD4 to control lineage-specifying genes.</strong> Nature 557: 739-743, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29795351/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29795351</a>] [<a href="https://doi.org/10.1038/s41586-018-0153-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29795351">Ostapcuk et al. (2018)</a> showed that ADNP (<a href="/entry/611386">611386</a>) interacts with the chromatin remodeler CHD4 and the chromatin architectural protein HP1 (<a href="/entry/604478">604478</a>) to form a stable complex, which they referred to as ChAHP. Besides mediating complex assembly, ADNP recognizes DNA motifs that specify binding of ChAHP to euchromatin. Genetic ablation of ChAHP components in mouse embryonic stem cells resulted in spontaneous differentiation concomitant with premature activation of lineage-specific genes and in a failure to differentiate towards the neuronal lineage. Molecularly, ChAHP-mediated repression is fundamentally different from canonical HP1-mediated silencing: HP1 proteins, in conjunction with histone H3 lysine-9 trimethylation (H3K9me3), are thought to assemble broad heterochromatin domains that are refractory to transcription. ChAHP-mediated repression, however, acts in a locally restricted manner by establishing inaccessible chromatin around its DNA-binding sites and does not depend on H3K9me3-modified nucleosomes. <a href="#3" class="mim-tip-reference" title="Ostapcuk, V., Mohn, F., Carl, S. H., Basters, A., Hess, D., Iesmantavicius, V., Lampersberger, L., Flemr, M., Pandey, A., Thoma, N. H., Betschinger, J., Buhler, M. <strong>Activity-dependent neuroprotective protein recruits HP1 and CHD4 to control lineage-specifying genes.</strong> Nature 557: 739-743, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29795351/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29795351</a>] [<a href="https://doi.org/10.1038/s41586-018-0153-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29795351">Ostapcuk et al. (2018)</a> concluded that their results revealed that ADNP, via the recruitment of HP1 and CHD4, regulates the expression of genes that are crucial for maintaining distinct cellular states and assures accurate cell fate decisions upon external cues. Such a general role of ChAHP in governing cell fate plasticity may explain why ADNP mutations affect several organs and body functions and contribute to cancer progression. <a href="#3" class="mim-tip-reference" title="Ostapcuk, V., Mohn, F., Carl, S. H., Basters, A., Hess, D., Iesmantavicius, V., Lampersberger, L., Flemr, M., Pandey, A., Thoma, N. H., Betschinger, J., Buhler, M. <strong>Activity-dependent neuroprotective protein recruits HP1 and CHD4 to control lineage-specifying genes.</strong> Nature 557: 739-743, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29795351/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29795351</a>] [<a href="https://doi.org/10.1038/s41586-018-0153-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29795351">Ostapcuk et al. (2018)</a> found that the integrity of the ChAHP complex is disrupted by nonsense mutations identified in patients with Helsmoortel-Van der Aa syndrome (<a href="/entry/615873">615873</a>), and this could be rescued by aminoglycosides that suppress translation termination. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29795351" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using a CRISPR screen, <a href="#1" class="mim-tip-reference" title="Lan, X., Ren, R., Feng, R., Ly, L. C., Lan, Y., Zhang, Z., Aboreden, N., Qin, K., Horton, J. R., Grevet, J. D., Mayuranathan, T., Abdulmalik, O., Keller, C. A., Giardine, B., Hardison, R. C., Crossley, M., Weiss, M. J., Cheng, X., Cheng, X., Shi, J., Blobel, G. A. <strong>ZNF410 uniquely activates the NuRD component CHD4 to silence fetal hemoglobin expression.</strong> Molec. Cell 81: 239-254, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33301730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33301730</a>] [<a href="https://doi.org/10.1016/j.molcel.2020.11.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33301730">Lan et al. (2021)</a> identified ZNF410 (<a href="/entry/619427">619427</a>) as a repressor of gamma-globin (see <a href="/entry/142250">142250</a>) gene expression in HUDEP2 human erythroid cells. Depletion of ZNF410 in primary human erythroblasts elevated the gamma-globin levels. ZNF410 directly targeted the CHD4 gene in erythroid cells and repressed transcription of gamma-globin by modulating CHD4 expression. ZNF410 bound to chromatin at 2 unique, highly conserved dense site clusters near the CHD4 gene. The zinc finger domain of ZNF410 was necessary and sufficient for binding to DNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33301730" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using a CRISPR screen, <a href="#8" class="mim-tip-reference" title="Vinjamur, D. S., Yao, Q., Cole, M. A., McGuckin, C., Ren, C., Zeng, J., Hossain, M., Luk, K., Wolfe, S. A., Pinello, L., Bauer, D. E. <strong>ZNF410 represses fetal globin by singular control of CHD4.</strong> Nature Genet. 53: 719-728, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33859416/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33859416</a>] [<a href="https://doi.org/10.1038/s41588-021-00843-w" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33859416">Vinjamur et al. (2021)</a> independently identified ZNF410 as a repressor of fetal hemoglobin (HbF) in HUDEP2 cells. They validated the finding by knockout analysis in HUDEP2 cells and primary adult erythroid precursors. ZNF410 did not bind directly to the genes encoding HbF subunit gamma-globins. Instead, ZNF410 repressed gamma-globins exclusively by binding upstream elements and transactivating CHD4. ZNF410 chromatin occupancy was solely restricted to the CHD4 locus, which contained 2 ZNF410-bound regulatory elements with 27 combined ZNF410-binding motifs. Analysis of chromatin occupancy of endogenous Zfp410 in a mouse erythroid cell line showed results similar to those observed in human erythroid precursors, indicating that ZNF410 is an evolutionarily conserved HbF repressor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33859416" 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 fluorescence in situ hybridization, <a href="#4" class="mim-tip-reference" title="Seelig, H. P., Moosbrugger, I., Ehrfeld, H., Fink, T., Renz, M., Genth, E. <strong>The major dermatomyositis-specific Mi-2 autoantigen is a presumed helicase involved in transcriptional activation.</strong> Arthritis Rheum. 38: 1389-1399, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7575689/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7575689</a>] [<a href="https://doi.org/10.1002/art.1780381006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7575689">Seelig et al. (1995)</a> mapped the CHD4 gene to chromosome 12p13. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7575689" 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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In 5 unrelated patients with Sifrim-Hitz-Weiss syndrome (SIHIWES; <a href="/entry/617159">617159</a>), <a href="#7" class="mim-tip-reference" title="Sifrim, A., Hitz, M.-P., Wilsdon, A., Breckpot, J., Al Turki, S. H., Thienpont, B., McRae, J., Fitzgerald, T. W., Singh, T., Swaminathan, G. J., Prigmore, E., Rajan, D., and 63 others. <strong>Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing.</strong> Nature Genet. 48: 1060-1065, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27479907/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27479907</a>] [<a href="https://doi.org/10.1038/ng.3627" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27479907">Sifrim et al. (2016)</a> identified 5 different de novo heterozygous mutations in the CHD4 gene (see, e.g., <a href="#0001">603277.0001</a>-<a href="#0003">603277.0003</a>). There were 4 missense mutations and 1 in-frame deletion. Functional studies of the variants and studies of patient cells were not performed. The patients were ascertained from a cohort of 518 trios in which a child had syndromic congenital heart defects who underwent exome sequencing. Statistical analysis indicated that de novo mutations in the CHD4 gene were significantly enriched in patients compared to those expected under a null mutational model (p = 2.28 x 10(-7), Bonferroni-corrected p = 0.05). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27479907" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 5 unrelated patients with SIHIWES, <a href="#10" class="mim-tip-reference" title="Weiss, K., Terhal, P. A., Cohen, L., Bruccoleri, M., Irving, M., Martinez, A. F., Rosenfeld, J. A., Machol, K., Yang, Y., Liu, P., Walkiewicz, M., Beuten, J., and 16 others. <strong>De novo mutations in CHD4, an ATP-dependent chromatin remodeler gene, cause an intellectual disability syndrome with distinctive dysmorphisms.</strong> Am. J. Hum. Genet. 99: 934-941, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27616479/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27616479</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27616479[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.08.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27616479">Weiss et al. (2016)</a> identified 4 different de novo heterozygous missense mutations in the CHD4 gene (see, e.g., <a href="#0004">603277.0004</a>-<a href="#0006">603277.0006</a>). The mutations were found by whole-exome sequencing and confirmed by Sanger sequencing. Three of the mutations occurred at highly conserved residues in the C-terminal helicase domain and were predicted to disrupt the ATPase activity of CHD4. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27616479" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Somatic Mutations</em></strong></p><p>
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<a href="#2" class="mim-tip-reference" title="Le Gallo, M., O'Hara, A. J., Rudd, M. L., Urick, M. E., Hansen, N. F., O'Neil, N. J., Price, J. C., Zhang, S., England, B. M., Godwin, A. K., Sgroi, D. C., NIH Intramural Sequencing Center (NISC) Comparative Sequencing Program, Hieter, P., Mullikan, J. C., Merino, M. J., Bell, D. W. <strong>Exome sequencing of serous endometrial tumors identifies recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes.</strong> Nature Genet. 44: 1310-1315, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23104009/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23104009</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23104009[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/ng.2455" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23104009">Le Gallo et al. (2012)</a> used whole-exome sequencing to comprehensively search for somatic mutations in 13 primary serous endometrial tumors (see <a href="/entry/608089">608089</a>), and subsequently resequenced 18 genes that were mutated in more than 1 tumor and/or were components of an enriched functional grouping from 40 additional serous tumors. <a href="#2" class="mim-tip-reference" title="Le Gallo, M., O'Hara, A. J., Rudd, M. L., Urick, M. E., Hansen, N. F., O'Neil, N. J., Price, J. C., Zhang, S., England, B. M., Godwin, A. K., Sgroi, D. C., NIH Intramural Sequencing Center (NISC) Comparative Sequencing Program, Hieter, P., Mullikan, J. C., Merino, M. J., Bell, D. W. <strong>Exome sequencing of serous endometrial tumors identifies recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes.</strong> Nature Genet. 44: 1310-1315, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23104009/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23104009</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23104009[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/ng.2455" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23104009">Le Gallo et al. (2012)</a> identified a high frequency of somatic mutation in the CHD4 gene (17%). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23104009" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs201992075 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs201992075;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/rs201992075?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=rs201992075" 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=rs201992075" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a 3-year-old boy (patient 1) with Sifrim-Hitz-Weiss syndrome (SIHIWES; <a href="/entry/617159">617159</a>), <a href="#7" class="mim-tip-reference" title="Sifrim, A., Hitz, M.-P., Wilsdon, A., Breckpot, J., Al Turki, S. H., Thienpont, B., McRae, J., Fitzgerald, T. W., Singh, T., Swaminathan, G. J., Prigmore, E., Rajan, D., and 63 others. <strong>Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing.</strong> Nature Genet. 48: 1060-1065, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27479907/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27479907</a>] [<a href="https://doi.org/10.1038/ng.3627" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27479907">Sifrim et al. (2016)</a> identified a de novo heterozygous c.4822G-A transition (c.4822G-A, NM_001273.3) in the CHD4 gene, resulting in a val1608-to-ile (V1608I) substitution. The mutation was found by exome sequencing. Functional studies of the variant and studies of patient cells were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27479907" 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 16.9-year-old boy (patient 2) with Sifrim-Hitz-Weiss syndrome (SIHIWES; <a href="/entry/617159">617159</a>), <a href="#7" class="mim-tip-reference" title="Sifrim, A., Hitz, M.-P., Wilsdon, A., Breckpot, J., Al Turki, S. H., Thienpont, B., McRae, J., Fitzgerald, T. W., Singh, T., Swaminathan, G. J., Prigmore, E., Rajan, D., and 63 others. <strong>Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing.</strong> Nature Genet. 48: 1060-1065, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27479907/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27479907</a>] [<a href="https://doi.org/10.1038/ng.3627" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27479907">Sifrim et al. (2016)</a> identified a de novo heterozygous c.3203G-A transition (c.3203G-A, NM_001273.3) in the CHD4 gene, resulting in an arg1068-to-his (R1068H) substitution. Functional studies of the variant and studies of patient cells were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27479907" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs886039916 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs886039916;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=rs886039916" 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=rs886039916" 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=RCV000257090" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000257090" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000257090</a>
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<p>In an 11-year-old girl (patient 4) with Sifrim-Hitz-Weiss syndrome (SIHIWES; <a href="/entry/617159">617159</a>), <a href="#7" class="mim-tip-reference" title="Sifrim, A., Hitz, M.-P., Wilsdon, A., Breckpot, J., Al Turki, S. H., Thienpont, B., McRae, J., Fitzgerald, T. W., Singh, T., Swaminathan, G. J., Prigmore, E., Rajan, D., and 63 others. <strong>Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing.</strong> Nature Genet. 48: 1060-1065, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27479907/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27479907</a>] [<a href="https://doi.org/10.1038/ng.3627" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27479907">Sifrim et al. (2016)</a> identified a de novo heterozygous c.2552C-A transversion (c.2552C-A, NM_001273.3) in the CHD4 gene, resulting in a ser851-to-tyr (S851Y) substitution. Functional studies of the variant and studies of patient cells were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27479907" 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 SIFRIM-HITZ-WEISS SYNDROME</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">rs886039917 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs886039917;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=rs886039917" 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=rs886039917" 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=RCV000257626" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000257626" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000257626</a>
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<p>In 2 unrelated 10-year-old boys (patients 1 and 3) with Sifrim-Hitz-Weiss syndrome (SIHIWES; <a href="/entry/617159">617159</a>), <a href="#10" class="mim-tip-reference" title="Weiss, K., Terhal, P. A., Cohen, L., Bruccoleri, M., Irving, M., Martinez, A. F., Rosenfeld, J. A., Machol, K., Yang, Y., Liu, P., Walkiewicz, M., Beuten, J., and 16 others. <strong>De novo mutations in CHD4, an ATP-dependent chromatin remodeler gene, cause an intellectual disability syndrome with distinctive dysmorphisms.</strong> Am. J. Hum. Genet. 99: 934-941, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27616479/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27616479</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27616479[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.08.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27616479">Weiss et al. (2016)</a> identified a de novo heterozygous c.3380G-A transition (c.3380G-A, NM_001273.3) in the CHD4 gene, resulting in an arg1127-to-gln (R1127Q) substitution at a highly conserved residue in the C terminal helicase domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the ExAC database. Coimmunoprecipitation studies and Western blot analysis showed that the mutant protein localized properly to the nucleus and interacted normally with HDAC1 (<a href="/entry/601241">601241</a>), suggesting that the mutation did not affect CHD4 complex formation. However, the substitution was predicted to disrupt ATPase activity. Patient 1 also carried a de novo heterozygous missense variant in the APOBEC1 gene (<a href="/entry/600130">600130</a>) that was predicted to be deleterious, and patient 3 carried several additional variants in other genes that were inherited from an unaffected parent. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27616479" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 SIFRIM-HITZ-WEISS SYNDROME</strong>
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CHD4, ARG1173LEU
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs886039918 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs886039918;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=rs886039918" 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=rs886039918" 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=RCV000256716" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000256716" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000256716</a>
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<p>In a 16-year-old girl (patient 2) with Sifrim-Hitz-Weiss syndrome (SIHIWES; <a href="/entry/617159">617159</a>), <a href="#10" class="mim-tip-reference" title="Weiss, K., Terhal, P. A., Cohen, L., Bruccoleri, M., Irving, M., Martinez, A. F., Rosenfeld, J. A., Machol, K., Yang, Y., Liu, P., Walkiewicz, M., Beuten, J., and 16 others. <strong>De novo mutations in CHD4, an ATP-dependent chromatin remodeler gene, cause an intellectual disability syndrome with distinctive dysmorphisms.</strong> Am. J. Hum. Genet. 99: 934-941, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27616479/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27616479</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27616479[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.08.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27616479">Weiss et al. (2016)</a> identified a de novo heterozygous c.3518G-T transversion (c.3518G-T, NM_001273.3) in the CHD4 gene, resulting in an arg1173-to-leu (R1173L) substitution at a highly conserved residue in the C-terminal helicase domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the ExAC database. Coimmunoprecipitation studies and Western blot analysis showed that the mutant protein localized properly to the nucleus and interacted normally with HDAC1 (<a href="/entry/601241">601241</a>), suggesting that the mutation does not affect CHD4 complex formation. However, the substitution was predicted to disrupt ATPase activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27616479" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0006" class="mim-anchor"></a>
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<strong>.0006 SIFRIM-HITZ-WEISS SYNDROME</strong>
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CHD4, TRP1148LEU
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs886039919 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs886039919;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=rs886039919" 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=rs886039919" 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=RCV000257253" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000257253" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000257253</a>
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<p>In a 5-year-old girl (patient 4) with Sifrim-Hitz-Weiss syndrome (SIHIWES; <a href="/entry/617159">617159</a>), <a href="#10" class="mim-tip-reference" title="Weiss, K., Terhal, P. A., Cohen, L., Bruccoleri, M., Irving, M., Martinez, A. F., Rosenfeld, J. A., Machol, K., Yang, Y., Liu, P., Walkiewicz, M., Beuten, J., and 16 others. <strong>De novo mutations in CHD4, an ATP-dependent chromatin remodeler gene, cause an intellectual disability syndrome with distinctive dysmorphisms.</strong> Am. J. Hum. Genet. 99: 934-941, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27616479/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27616479</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27616479[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.08.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27616479">Weiss et al. (2016)</a> identified a de novo heterozygous c.3443G-T transversion (c.3443G-T, NM_001273.3) in the CHD4 gene, resulting in a trp1148-to-leu (W1148L) substitution at a highly conserved residue in the C-terminal helicase domain. The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. Functional studies of the variant and studies on patient cells were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27616479" 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 id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>REFERENCES</strong>
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Lan, X., Ren, R., Feng, R., Ly, L. C., Lan, Y., Zhang, Z., Aboreden, N., Qin, K., Horton, J. R., Grevet, J. D., Mayuranathan, T., Abdulmalik, O., Keller, C. A., Giardine, B., Hardison, R. C., Crossley, M., Weiss, M. J., Cheng, X., Cheng, X., Shi, J., Blobel, G. A.
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<strong>ZNF410 uniquely activates the NuRD component CHD4 to silence fetal hemoglobin expression.</strong>
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Molec. Cell 81: 239-254, 2021.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33301730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33301730</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33301730" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.molcel.2020.11.006" target="_blank">Full Text</a>]
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Le Gallo, M., O'Hara, A. J., Rudd, M. L., Urick, M. E., Hansen, N. F., O'Neil, N. J., Price, J. C., Zhang, S., England, B. M., Godwin, A. K., Sgroi, D. C., NIH Intramural Sequencing Center (NISC) Comparative Sequencing Program, Hieter, P., Mullikan, J. C., Merino, M. J., Bell, D. W.
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<strong>Exome sequencing of serous endometrial tumors identifies recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes.</strong>
|
|
Nature Genet. 44: 1310-1315, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23104009/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23104009</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23104009[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=23104009" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng.2455" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Ostapcuk2018" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ostapcuk, V., Mohn, F., Carl, S. H., Basters, A., Hess, D., Iesmantavicius, V., Lampersberger, L., Flemr, M., Pandey, A., Thoma, N. H., Betschinger, J., Buhler, M.
|
|
<strong>Activity-dependent neuroprotective protein recruits HP1 and CHD4 to control lineage-specifying genes.</strong>
|
|
Nature 557: 739-743, 2018.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29795351/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29795351</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29795351" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/s41586-018-0153-8" target="_blank">Full Text</a>]
|
|
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|
</p>
|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Seelig1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Seelig, H. P., Moosbrugger, I., Ehrfeld, H., Fink, T., Renz, M., Genth, E.
|
|
<strong>The major dermatomyositis-specific Mi-2 autoantigen is a presumed helicase involved in transcriptional activation.</strong>
|
|
Arthritis Rheum. 38: 1389-1399, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7575689/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7575689</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7575689" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/art.1780381006" target="_blank">Full Text</a>]
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|
|
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|
|
|
|
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|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Seelig1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Seelig, H. P., Renz, M., Targoff, I. N., Ge, Q., Frank, M. B.
|
|
<strong>Two forms of the major antigenic protein of the dermatomyositis-specific Mi-2 autoantigen. (Letter)</strong>
|
|
Arthritis Rheum. 39: 1769-1771, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8843877/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8843877</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8843877" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1002/art.1780391029" target="_blank">Full Text</a>]
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|
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|
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|
|
|
|
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|
|
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|
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<a id="Shimono2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shimono, K., Shimono, Y., Shimokata, K., Ishiguro, N., Takahashi, M.
|
|
<strong>Microspherule protein 1, Mi-2-beta, and RET finger protein associate in the nucleolus and up-regulate ribosomal gene transcription.</strong>
|
|
J. Biol. Chem. 280: 39436-39447, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16186106/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16186106</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16186106" 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.M507356200" target="_blank">Full Text</a>]
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|
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|
|
|
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|
|
<a id="7" class="mim-anchor"></a>
|
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<a id="Sifrim2016" class="mim-anchor"></a>
|
|
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|
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Sifrim, A., Hitz, M.-P., Wilsdon, A., Breckpot, J., Al Turki, S. H., Thienpont, B., McRae, J., Fitzgerald, T. W., Singh, T., Swaminathan, G. J., Prigmore, E., Rajan, D., and 63 others.
|
|
<strong>Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing.</strong>
|
|
Nature Genet. 48: 1060-1065, 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27479907/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27479907</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27479907" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng.3627" target="_blank">Full Text</a>]
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<a id="Vinjamur2021" class="mim-anchor"></a>
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Vinjamur, D. S., Yao, Q., Cole, M. A., McGuckin, C., Ren, C., Zeng, J., Hossain, M., Luk, K., Wolfe, S. A., Pinello, L., Bauer, D. E.
|
|
<strong>ZNF410 represses fetal globin by singular control of CHD4.</strong>
|
|
Nature Genet. 53: 719-728, 2021.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33859416/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33859416</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33859416" 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/s41588-021-00843-w" target="_blank">Full Text</a>]
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<a id="9" class="mim-anchor"></a>
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<a id="Wade1999" class="mim-anchor"></a>
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Wade, P. A., Gegonne, A., Jones, P. L., Ballestar, E., Aubry, F., Wolffe, A. P.
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<strong>Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation.</strong>
|
|
Nature Genet. 23: 62-66, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10471500/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10471500</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10471500" 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/10.1038/12664" target="_blank">Full Text</a>]
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<a id="Weiss2016" class="mim-anchor"></a>
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|
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Weiss, K., Terhal, P. A., Cohen, L., Bruccoleri, M., Irving, M., Martinez, A. F., Rosenfeld, J. A., Machol, K., Yang, Y., Liu, P., Walkiewicz, M., Beuten, J., and 16 others.
|
|
<strong>De novo mutations in CHD4, an ATP-dependent chromatin remodeler gene, cause an intellectual disability syndrome with distinctive dysmorphisms.</strong>
|
|
Am. J. Hum. Genet. 99: 934-941, 2016.
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|
|
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27616479/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27616479</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27616479[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=27616479" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ajhg.2016.08.001" target="_blank">Full Text</a>]
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<a id="Zhang1998" class="mim-anchor"></a>
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<p class="mim-text-font">
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Zhang, Y., LeRoy, G., Seelig, H.-P., Lane, W. S., Reinberg, D.
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<strong>The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities.</strong>
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|
Cell 95: 279-289, 1998.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9790534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9790534</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9790534" 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/s0092-8674(00)81758-4" target="_blank">Full Text</a>]
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<a id="Zhang1999" class="mim-anchor"></a>
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Zhang, Y., Ng, H.-H., Erdjument-Bromage, H., Tempst, P., Bird, A., Reinberg, D.
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<strong>Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation.</strong>
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Genes Dev. 13: 1924-1935, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10444591/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10444591</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10444591[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=10444591" 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/10.1101/gad.13.15.1924" 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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Bao Lige - updated : 07/12/2021
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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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Ada Hamosh - updated : 08/20/2018<br>Cassandra L. Kniffin - updated : 10/18/2016<br>Ada Hamosh - updated : 2/7/2013<br>Paul J. Converse - updated : 11/6/2006<br>Paul J. Converse - updated : 1/11/2002<br>Stylianos E. Antonarakis - updated : 11/25/1998
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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 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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Patti M. Sherman : 11/11/1998
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<span class="mim-text-font">
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mgross : 07/12/2021
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<span class="mim-text-font">
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alopez : 08/20/2018<br>carol : 01/24/2017<br>carol : 10/19/2016<br>carol : 10/18/2016<br>ckniffin : 10/18/2016<br>carol : 04/11/2016<br>alopez : 2/7/2013<br>mgross : 11/3/2010<br>mgross : 11/6/2006<br>mgross : 11/6/2006<br>mgross : 1/11/2002<br>carol : 11/25/1998<br>carol : 11/25/1998
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<h3>
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<span class="mim-font">
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<strong>*</strong> 603277
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<h3>
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<span class="mim-font">
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CHROMODOMAIN HELICASE DNA-BINDING PROTEIN 4; CHD4
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<h4>
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<span class="mim-font">
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Mi2-BETA
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<strong><em>HGNC Approved Gene Symbol: CHD4</em></strong>
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</span>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 1332510002;
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</span>
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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: 12p13.31
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Genomic coordinates <span class="small">(GRCh38)</span> : 12:6,570,082-6,607,379 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
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</p>
|
|
</div>
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<div>
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<br />
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
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<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
12p13.31
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Sifrim-Hitz-Weiss syndrome
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
617159
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
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</tr>
|
|
|
|
|
|
</tbody>
|
|
</table>
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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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|
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<h4>
|
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<span class="mim-font">
|
|
<strong>TEXT</strong>
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</span>
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</h4>
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<div>
|
|
<h4>
|
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<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<span class="mim-text-font">
|
|
<p>The CHD4 gene encodes a chromodomain-containing protein that catalyzes ATP-dependent chromatin remodeling as a core component of the nucleosome remodeling and histone deacetylase (NURD) repressor complex, which is involved in epigenetic regulation of gene transcription, DNA repair, and cell cycle progression (summary by Sifrim et al., 2016 and Weiss et al., 2016). </p>
|
|
</span>
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|
<div>
|
|
<br />
|
|
</div>
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
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|
|
<span class="mim-text-font">
|
|
<p>Approximately 20% of patients with dermatomyositis develop antibodies against nuclear antigens that are termed Mi2. Sera containing anti-Mi2 antibodies precipitate several proteins, with 1 of the most abundant migrating as a 220- to 260-kD polypeptide on SDS-polyacrylamide gels. By immunoscreening a HeLa cell cDNA expression library with sera from a patient with dermatomyositis, Seelig et al. (1995) isolated a full-length cDNA encoding CHD4, which they called Mi2-beta. Northern blot analysis of Hep-2 cell RNA detected an approximately 6.8-kb Mi2-beta transcript. The deduced 1,912-amino acid protein has a calculated molecular mass of 218 kD. Native Mi2-beta from Hep-2 cells has a molecular mass of 235 kD by SDS-PAGE. Searches of sequence databases indicated that Mi2-beta belongs to the SNF2/RAD54 family of nuclear helicases. The central portion of Mi2-beta contains the 7 motifs, including a DEAD/H box, that are characteristic of helicases. Mi2-beta also contains a putative chromatin-binding region and multiple potential nuclear targeting signals, N-glycosylation sites, N-myristoylation sites, and phosphorylation sites. Immunofluorescence studies localized the Mi2-beta protein to the nucleus. The authors concluded that Mi2-beta is a major antigen recognized by anti-Mi2 sera from patients with dermatomyositis. Studies with sera from dermatomyositis, systemic lupus erythematosus (152700), and rheumatoid arthritis (180300) patients showed that anti-Mi2-beta antibodies are predominantly found in dermatomyositis patients. </p><p>Seelig et al. (1996) noted that the Mi2-alpha (CHD3; 602120) and Mi2-beta proteins react with most or all dermatomyositis patient anti-Mi2 sera. While these proteins are distinct, they have stretches of identical sequences that could result in shared epitopes. The authors stated that Mi2-alpha and Mi2-beta contain a PHD motif, which is a zinc finger-like motif with a cys4-his-cys3 pattern and which is thought to be a DNA- or RNA-binding domain. </p>
|
|
</span>
|
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<div>
|
|
<br />
|
|
</div>
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|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Family</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>See CHD1 (602118) for a description of this gene family.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
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<span class="mim-text-font">
|
|
<p>Zhang et al. (1998) reported the isolation of a protein complex that contains both histone deacetylation and ATP-dependent nucleosome remodeling activities. The complex contained the histone deacetylases HDAC1/2, histone-binding proteins, the dermatomyositis-specific autoantigen Mi2-beta, a polypeptide related to the metastasis-associated protein-1, and a novel polypeptide of 32 kD. Patients with dermatomyositis have a high rate of malignancy. The finding that Mi2-beta exists in a complex containing histone deacetylase and nucleosome remodeling activities suggests a role for chromatin reorganization in cancer metastasis. </p><p>Zhang et al. (1999) showed that MTA2 (MTA1L1; 603947) and the 32-kD MBD3 (603573) protein are subunits of the NURD (nucleosome remodeling and histone deacetylase) complex (see MTA1; 603526). Immunoprecipitation analysis showed that MBD3 interacts with HDAC1 (601241), RBBP4 (602923), and RBBP7 (300825), but not with MI2, suggesting that MBD3 is embedded within the NURD complex. The authors found that MTA2 directs the assembly of an active histone deacetylase complex and that the association of MTA2 with the complex requires MBD3. Gel mobility shift analysis determined that both NURD and MBD3 are unable to bind to methylated DNA in the absence of MBD2 (603547). Zhang et al. (1999) proposed that NURD is involved in the transcriptional repression of methylated DNA. Wade et al. (1999) also identified MTA1, MTA1L, and MBD3 as components of the NURD complex, which they referred to as the MI2 complex. </p><p>By immunoprecipitation analysis, Shimono et al. (2005) found that MCRS1 (609504) interacted with MI2-beta, RFP (TRIM27; 602165), and UBF (UBTF; 600673). Yeast 2-hybrid screening showed that the central region of MCRS1 interacted with the ATPase/helicase region of MI2-beta and the coiled-coil region of RFP. Confocal microscopy demonstrated colocalization of MCRS1, MI2-beta, RFP, and UBF in nucleoli. Chromatin immunoprecipitation assays showed that MCRS1, MI2-beta, and RFP associated with rDNA and were involved in transactivation of ribosomal gene transcription, which could be downregulated by small interfering RNA-mediated downregulation of MCRS1, MI2-beta, and RFP. Shimono et al. (2005) concluded that MI2-beta and RFP, which are involved in transcriptional repression in the nucleus, associate with MCRS1 in the nucleolus and are involved in activation of rRNA transcription. </p><p>Ostapcuk et al. (2018) showed that ADNP (611386) interacts with the chromatin remodeler CHD4 and the chromatin architectural protein HP1 (604478) to form a stable complex, which they referred to as ChAHP. Besides mediating complex assembly, ADNP recognizes DNA motifs that specify binding of ChAHP to euchromatin. Genetic ablation of ChAHP components in mouse embryonic stem cells resulted in spontaneous differentiation concomitant with premature activation of lineage-specific genes and in a failure to differentiate towards the neuronal lineage. Molecularly, ChAHP-mediated repression is fundamentally different from canonical HP1-mediated silencing: HP1 proteins, in conjunction with histone H3 lysine-9 trimethylation (H3K9me3), are thought to assemble broad heterochromatin domains that are refractory to transcription. ChAHP-mediated repression, however, acts in a locally restricted manner by establishing inaccessible chromatin around its DNA-binding sites and does not depend on H3K9me3-modified nucleosomes. Ostapcuk et al. (2018) concluded that their results revealed that ADNP, via the recruitment of HP1 and CHD4, regulates the expression of genes that are crucial for maintaining distinct cellular states and assures accurate cell fate decisions upon external cues. Such a general role of ChAHP in governing cell fate plasticity may explain why ADNP mutations affect several organs and body functions and contribute to cancer progression. Ostapcuk et al. (2018) found that the integrity of the ChAHP complex is disrupted by nonsense mutations identified in patients with Helsmoortel-Van der Aa syndrome (615873), and this could be rescued by aminoglycosides that suppress translation termination. </p><p>Using a CRISPR screen, Lan et al. (2021) identified ZNF410 (619427) as a repressor of gamma-globin (see 142250) gene expression in HUDEP2 human erythroid cells. Depletion of ZNF410 in primary human erythroblasts elevated the gamma-globin levels. ZNF410 directly targeted the CHD4 gene in erythroid cells and repressed transcription of gamma-globin by modulating CHD4 expression. ZNF410 bound to chromatin at 2 unique, highly conserved dense site clusters near the CHD4 gene. The zinc finger domain of ZNF410 was necessary and sufficient for binding to DNA. </p><p>Using a CRISPR screen, Vinjamur et al. (2021) independently identified ZNF410 as a repressor of fetal hemoglobin (HbF) in HUDEP2 cells. They validated the finding by knockout analysis in HUDEP2 cells and primary adult erythroid precursors. ZNF410 did not bind directly to the genes encoding HbF subunit gamma-globins. Instead, ZNF410 repressed gamma-globins exclusively by binding upstream elements and transactivating CHD4. ZNF410 chromatin occupancy was solely restricted to the CHD4 locus, which contained 2 ZNF410-bound regulatory elements with 27 combined ZNF410-binding motifs. Analysis of chromatin occupancy of endogenous Zfp410 in a mouse erythroid cell line showed results similar to those observed in human erythroid precursors, indicating that ZNF410 is an evolutionarily conserved HbF repressor. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By fluorescence in situ hybridization, Seelig et al. (1995) mapped the CHD4 gene to chromosome 12p13. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Sifrim-Hitz-Weiss Syndrome</em></strong></p><p>
|
|
In 5 unrelated patients with Sifrim-Hitz-Weiss syndrome (SIHIWES; 617159), Sifrim et al. (2016) identified 5 different de novo heterozygous mutations in the CHD4 gene (see, e.g., 603277.0001-603277.0003). There were 4 missense mutations and 1 in-frame deletion. Functional studies of the variants and studies of patient cells were not performed. The patients were ascertained from a cohort of 518 trios in which a child had syndromic congenital heart defects who underwent exome sequencing. Statistical analysis indicated that de novo mutations in the CHD4 gene were significantly enriched in patients compared to those expected under a null mutational model (p = 2.28 x 10(-7), Bonferroni-corrected p = 0.05). </p><p>In 5 unrelated patients with SIHIWES, Weiss et al. (2016) identified 4 different de novo heterozygous missense mutations in the CHD4 gene (see, e.g., 603277.0004-603277.0006). The mutations were found by whole-exome sequencing and confirmed by Sanger sequencing. Three of the mutations occurred at highly conserved residues in the C-terminal helicase domain and were predicted to disrupt the ATPase activity of CHD4. </p><p><strong><em>Somatic Mutations</em></strong></p><p>
|
|
Le Gallo et al. (2012) used whole-exome sequencing to comprehensively search for somatic mutations in 13 primary serous endometrial tumors (see 608089), and subsequently resequenced 18 genes that were mutated in more than 1 tumor and/or were components of an enriched functional grouping from 40 additional serous tumors. Le Gallo et al. (2012) identified a high frequency of somatic mutation in the CHD4 gene (17%). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>6 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 SIFRIM-HITZ-WEISS SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CHD4, VAL1608ILE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs201992075,
|
|
|
|
|
|
gnomAD: rs201992075,
|
|
|
|
|
|
ClinVar: RCV000257639
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 3-year-old boy (patient 1) with Sifrim-Hitz-Weiss syndrome (SIHIWES; 617159), Sifrim et al. (2016) identified a de novo heterozygous c.4822G-A transition (c.4822G-A, NM_001273.3) in the CHD4 gene, resulting in a val1608-to-ile (V1608I) substitution. The mutation was found by exome sequencing. Functional studies of the variant and studies of patient cells were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 SIFRIM-HITZ-WEISS SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CHD4, ARG1068HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs886039915,
|
|
|
|
|
|
|
|
ClinVar: RCV000256595, RCV000624678
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 16.9-year-old boy (patient 2) with Sifrim-Hitz-Weiss syndrome (SIHIWES; 617159), Sifrim et al. (2016) identified a de novo heterozygous c.3203G-A transition (c.3203G-A, NM_001273.3) in the CHD4 gene, resulting in an arg1068-to-his (R1068H) substitution. Functional studies of the variant and studies of patient cells were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 SIFRIM-HITZ-WEISS SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CHD4, SER851TYR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs886039916,
|
|
|
|
|
|
|
|
ClinVar: RCV000257090
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an 11-year-old girl (patient 4) with Sifrim-Hitz-Weiss syndrome (SIHIWES; 617159), Sifrim et al. (2016) identified a de novo heterozygous c.2552C-A transversion (c.2552C-A, NM_001273.3) in the CHD4 gene, resulting in a ser851-to-tyr (S851Y) substitution. Functional studies of the variant and studies of patient cells were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 SIFRIM-HITZ-WEISS SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CHD4, ARG1127GLN
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|
|
|
|
<br />
|
|
|
|
SNP: rs886039917,
|
|
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|
|
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ClinVar: RCV000257626
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 unrelated 10-year-old boys (patients 1 and 3) with Sifrim-Hitz-Weiss syndrome (SIHIWES; 617159), Weiss et al. (2016) identified a de novo heterozygous c.3380G-A transition (c.3380G-A, NM_001273.3) in the CHD4 gene, resulting in an arg1127-to-gln (R1127Q) substitution at a highly conserved residue in the C terminal helicase domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the ExAC database. Coimmunoprecipitation studies and Western blot analysis showed that the mutant protein localized properly to the nucleus and interacted normally with HDAC1 (601241), suggesting that the mutation did not affect CHD4 complex formation. However, the substitution was predicted to disrupt ATPase activity. Patient 1 also carried a de novo heterozygous missense variant in the APOBEC1 gene (600130) that was predicted to be deleterious, and patient 3 carried several additional variants in other genes that were inherited from an unaffected parent. </p>
|
|
</span>
|
|
</div>
|
|
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|
|
|
<div>
|
|
<br />
|
|
</div>
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</div>
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|
|
<div>
|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 SIFRIM-HITZ-WEISS SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
CHD4, ARG1173LEU
|
|
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|
|
|
<br />
|
|
|
|
SNP: rs886039918,
|
|
|
|
|
|
|
|
ClinVar: RCV000256716
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 16-year-old girl (patient 2) with Sifrim-Hitz-Weiss syndrome (SIHIWES; 617159), Weiss et al. (2016) identified a de novo heterozygous c.3518G-T transversion (c.3518G-T, NM_001273.3) in the CHD4 gene, resulting in an arg1173-to-leu (R1173L) substitution at a highly conserved residue in the C-terminal helicase domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the ExAC database. Coimmunoprecipitation studies and Western blot analysis showed that the mutant protein localized properly to the nucleus and interacted normally with HDAC1 (601241), suggesting that the mutation does not affect CHD4 complex formation. However, the substitution was predicted to disrupt ATPase activity. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 SIFRIM-HITZ-WEISS SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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|
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|
<div>
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<span class="mim-text-font">
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CHD4, TRP1148LEU
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<br />
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SNP: rs886039919,
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ClinVar: RCV000257253
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<p>In a 5-year-old girl (patient 4) with Sifrim-Hitz-Weiss syndrome (SIHIWES; 617159), Weiss et al. (2016) identified a de novo heterozygous c.3443G-T transversion (c.3443G-T, NM_001273.3) in the CHD4 gene, resulting in a trp1148-to-leu (W1148L) substitution at a highly conserved residue in the C-terminal helicase domain. The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. Functional studies of the variant and studies on patient cells were not performed. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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</div>
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<ol>
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<p class="mim-text-font">
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Lan, X., Ren, R., Feng, R., Ly, L. C., Lan, Y., Zhang, Z., Aboreden, N., Qin, K., Horton, J. R., Grevet, J. D., Mayuranathan, T., Abdulmalik, O., Keller, C. A., Giardine, B., Hardison, R. C., Crossley, M., Weiss, M. J., Cheng, X., Cheng, X., Shi, J., Blobel, G. A.
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<strong>ZNF410 uniquely activates the NuRD component CHD4 to silence fetal hemoglobin expression.</strong>
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Molec. Cell 81: 239-254, 2021.
|
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[PubMed: 33301730]
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[Full Text: https://doi.org/10.1016/j.molcel.2020.11.006]
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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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Le Gallo, M., O'Hara, A. J., Rudd, M. L., Urick, M. E., Hansen, N. F., O'Neil, N. J., Price, J. C., Zhang, S., England, B. M., Godwin, A. K., Sgroi, D. C., NIH Intramural Sequencing Center (NISC) Comparative Sequencing Program, Hieter, P., Mullikan, J. C., Merino, M. J., Bell, D. W.
|
|
<strong>Exome sequencing of serous endometrial tumors identifies recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes.</strong>
|
|
Nature Genet. 44: 1310-1315, 2012.
|
|
|
|
|
|
[PubMed: 23104009]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng.2455]
|
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</p>
|
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</li>
|
|
|
|
<li>
|
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<p class="mim-text-font">
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Ostapcuk, V., Mohn, F., Carl, S. H., Basters, A., Hess, D., Iesmantavicius, V., Lampersberger, L., Flemr, M., Pandey, A., Thoma, N. H., Betschinger, J., Buhler, M.
|
|
<strong>Activity-dependent neuroprotective protein recruits HP1 and CHD4 to control lineage-specifying genes.</strong>
|
|
Nature 557: 739-743, 2018.
|
|
|
|
|
|
[PubMed: 29795351]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/s41586-018-0153-8]
|
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</p>
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</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
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Seelig, H. P., Moosbrugger, I., Ehrfeld, H., Fink, T., Renz, M., Genth, E.
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<strong>The major dermatomyositis-specific Mi-2 autoantigen is a presumed helicase involved in transcriptional activation.</strong>
|
|
Arthritis Rheum. 38: 1389-1399, 1995.
|
|
|
|
|
|
[PubMed: 7575689]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/art.1780381006]
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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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Seelig, H. P., Renz, M., Targoff, I. N., Ge, Q., Frank, M. B.
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<strong>Two forms of the major antigenic protein of the dermatomyositis-specific Mi-2 autoantigen. (Letter)</strong>
|
|
Arthritis Rheum. 39: 1769-1771, 1996.
|
|
|
|
|
|
[PubMed: 8843877]
|
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|
|
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[Full Text: https://doi.org/10.1002/art.1780391029]
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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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Shimono, K., Shimono, Y., Shimokata, K., Ishiguro, N., Takahashi, M.
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<strong>Microspherule protein 1, Mi-2-beta, and RET finger protein associate in the nucleolus and up-regulate ribosomal gene transcription.</strong>
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J. Biol. Chem. 280: 39436-39447, 2005.
|
|
|
|
|
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[PubMed: 16186106]
|
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|
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[Full Text: https://doi.org/10.1074/jbc.M507356200]
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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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Sifrim, A., Hitz, M.-P., Wilsdon, A., Breckpot, J., Al Turki, S. H., Thienpont, B., McRae, J., Fitzgerald, T. W., Singh, T., Swaminathan, G. J., Prigmore, E., Rajan, D., and 63 others.
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<strong>Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing.</strong>
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Nature Genet. 48: 1060-1065, 2016.
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[PubMed: 27479907]
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[Full Text: https://doi.org/10.1038/ng.3627]
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<li>
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Vinjamur, D. S., Yao, Q., Cole, M. A., McGuckin, C., Ren, C., Zeng, J., Hossain, M., Luk, K., Wolfe, S. A., Pinello, L., Bauer, D. E.
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<strong>ZNF410 represses fetal globin by singular control of CHD4.</strong>
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Nature Genet. 53: 719-728, 2021.
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[PubMed: 33859416]
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[Full Text: https://doi.org/10.1038/s41588-021-00843-w]
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</p>
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<li>
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Wade, P. A., Gegonne, A., Jones, P. L., Ballestar, E., Aubry, F., Wolffe, A. P.
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<strong>Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation.</strong>
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Nature Genet. 23: 62-66, 1999.
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[PubMed: 10471500]
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[Full Text: https://doi.org/10.1038/12664]
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</p>
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<li>
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<p class="mim-text-font">
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Weiss, K., Terhal, P. A., Cohen, L., Bruccoleri, M., Irving, M., Martinez, A. F., Rosenfeld, J. A., Machol, K., Yang, Y., Liu, P., Walkiewicz, M., Beuten, J., and 16 others.
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<strong>De novo mutations in CHD4, an ATP-dependent chromatin remodeler gene, cause an intellectual disability syndrome with distinctive dysmorphisms.</strong>
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Am. J. Hum. Genet. 99: 934-941, 2016.
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[PubMed: 27616479]
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[Full Text: https://doi.org/10.1016/j.ajhg.2016.08.001]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Zhang, Y., LeRoy, G., Seelig, H.-P., Lane, W. S., Reinberg, D.
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<strong>The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities.</strong>
|
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Cell 95: 279-289, 1998.
|
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[PubMed: 9790534]
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[Full Text: https://doi.org/10.1016/s0092-8674(00)81758-4]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Zhang, Y., Ng, H.-H., Erdjument-Bromage, H., Tempst, P., Bird, A., Reinberg, D.
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<strong>Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation.</strong>
|
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Genes Dev. 13: 1924-1935, 1999.
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[PubMed: 10444591]
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[Full Text: https://doi.org/10.1101/gad.13.15.1924]
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</p>
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</li>
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</ol>
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<div>
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<br />
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<div 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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Bao Lige - updated : 07/12/2021<br>Ada Hamosh - updated : 08/20/2018<br>Cassandra L. Kniffin - updated : 10/18/2016<br>Ada Hamosh - updated : 2/7/2013<br>Paul J. Converse - updated : 11/6/2006<br>Paul J. Converse - updated : 1/11/2002<br>Stylianos E. Antonarakis - updated : 11/25/1998
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