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Entry
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- *601128 - H3 HISTONE, FAMILY 3A; H3F3A
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*601128</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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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#geneFunction">Gene Function</a>
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<a href="#biochemicalFeatures">Biochemical Features</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/601128">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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<li role="presentation">
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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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</li>
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</ul>
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<div id="mimFloatingLinksMenu">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000163041;t=ENST00000366815" 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=3020" 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=601128" 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 class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</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=ENSG00000163041;t=ENST00000366815" 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_001379043,NM_001379045,NM_001379046,NM_001379047,NM_002107" 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_002107" 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=601128" 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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<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=03082&isoform_id=03082_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/H3-3A" 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/306848,306849,1166436,4433163,4504279,20810210,25058578,51859376,55977062,63102453,119590176,119590177,119590178,119590179,189053224,194374253,1821955808,1821955839,1821955865,1821955899" 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/P84243" 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=3020" 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=ENSG00000163041;t=ENST00000366815" 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=H3-3A" 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=H3-3A" 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+3020" 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/H3-3A" 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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<div><a href="https://www.ncbi.nlm.nih.gov/gene/3020" 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=chr1&hgg_gene=ENST00000366815.10&hgg_start=226061831&hgg_end=226072019&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 class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:4764" 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=601128[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=601128[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/H3-3A/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/ENSG00000163041" 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=H3-3A" 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=H3-3A" 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=H3-3A" 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=H3-3A&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/PA166351884" 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:4764" 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/FBgn0004828.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/search?q=MGI:1097686 MGI:1101768" 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/H3-3A#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/batch/summary?idType=MGI&ids=MGI:1097686 MGI:1101768" 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/3020/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=3020" 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=WBGene00001945;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00001945 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00001946;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00001946 </a></div>
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</div>
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<div><a href="https://zfin.org/ZDB-GENE-040426-1928" 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:3020" 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=H3-3A&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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601128
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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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H3 HISTONE, FAMILY 3A; H3F3A
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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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H3F3<br />
|
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H3.3A
|
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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">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=H3-3A" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">H3-3A</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/1/1757?start=-3&limit=10&highlight=1757">1q42.12</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr1:226061831-226072019&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'})">1:226,061,831-226,072,019</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>
|
|
<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>
|
|
Location
|
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</th>
|
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<th>
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Phenotype
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</th>
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<th>
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|
Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
|
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</th>
|
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<th>
|
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Phenotype <br /> mapping key
|
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</th>
|
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</tr>
|
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</thead>
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<tbody>
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<tr>
|
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<td rowspan="1">
|
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<span class="mim-font">
|
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<a href="/geneMap/1/1757?start=-3&limit=10&highlight=1757">
|
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1q42.12
|
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</a>
|
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</span>
|
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</td>
|
|
|
|
|
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<td>
|
|
<span class="mim-font">
|
|
Bryant-Li-Bhoj neurodevelopmental syndrome 1
|
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|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<a href="/entry/619720"> 619720 </a>
|
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|
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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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|
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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/601128" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/601128" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
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<br />
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</div>
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<p>Histones are the basic nuclear proteins responsible for the nucleosome structure within the chromosomal fiber in eukaryotes. Five classes of histone genes have been reported. Some classes are expressed only during S phase, while others are replication independent. The latter are referred to as replacement histones and are expressed in quiescent or terminally differentiated cells. H3.3 is a replacement histone that is encoded by 2 distinct replication-independent genes, H3.3A (H3F3A) and H3.3B (H3F3B; <a href="/entry/601058">601058</a>). The proteins encoded by the H3.3A and H3.3B genes are identical (summary by <a href="#20" class="mim-tip-reference" title="Wells, D., Hoffman, D., Kedes, L. <strong>Unusual structure, evolutionary conservation of non-coding sequences and numerous pseudogenes characterize the H3.3 histone multigene family.</strong> Nucleic Acids Res. 15: 2871-2889, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3031613/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3031613</a>] [<a href="https://doi.org/10.1093/nar/15.7.2871" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3031613">Wells et al. (1987)</a> and <a href="#1" class="mim-tip-reference" title="Albig, W., Bramlage, B., Gruber, K., Klobeck, H.-G., Kunz, J., Doenecke, D. <strong>The human replacement histone H3.3B gene (H3F3B).</strong> Genomics 30: 264-272, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8586426/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8586426</a>] [<a href="https://doi.org/10.1006/geno.1995.9878" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8586426">Albig et al. (1995)</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3031613+8586426" 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>For additional background information on histones, histone gene clusters, and the H3 histone family, see HIST1H3A (<a href="/entry/602810">602810</a>).</p>
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<p>Using an H3.3 pseudogene cDNA to probe a human fibroblast cDNA library, <a href="#21" class="mim-tip-reference" title="Wells, D., Kedes, L. <strong>Structure of a human histone cDNA: evidence that basally expressed histone genes have intervening sequences and encode polyadenylated mRNAs.</strong> Proc. Nat. Acad. Sci. 82: 2834-2838, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2859593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2859593</a>] [<a href="https://doi.org/10.1073/pnas.82.9.2834" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2859593">Wells and Kedes (1985)</a> cloned H3.3. The transcript contains a long 3-prime poly(A) tail, and the deduced protein contains 135 amino acids. The H3.3 protein has 5 amino acid changes compared with H3.1 (see <a href="/entry/602812">602812</a>), but their nucleotide sequences are more divergent. Northern blot analysis detected a transcript of about 1.2 kb in HeLa cell poly(A) RNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2859593" 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="#6" class="mim-tip-reference" title="Chalmers, M., Wells, D. <strong>Extreme sequence conservation characterizes the rabbit H3.3A histone cDNA.</strong> Nucleic Acids Res. 18: 3075, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2349118/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2349118</a>] [<a href="https://doi.org/10.1093/nar/18.10.3075" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2349118">Chalmers and Wells (1990)</a> showed that the rabbit H3.3a 3-prime untranslated region is 94% similar to the human sequence of <a href="#21" class="mim-tip-reference" title="Wells, D., Kedes, L. <strong>Structure of a human histone cDNA: evidence that basally expressed histone genes have intervening sequences and encode polyadenylated mRNAs.</strong> Proc. Nat. Acad. Sci. 82: 2834-2838, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2859593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2859593</a>] [<a href="https://doi.org/10.1073/pnas.82.9.2834" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2859593">Wells and Kedes (1985)</a>, indicating that evolutionary conservation extends beyond the coding region. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2859593+2349118" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#22" class="mim-tip-reference" title="Witt, O., Albig, W., Doenecke, D. <strong>Transcriptional regulation of the human replacement histone gene H3.3B.</strong> FEBS Lett. 408: 255-260, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9188772/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9188772</a>] [<a href="https://doi.org/10.1016/s0014-5793(97)00436-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9188772">Witt et al. (1997)</a> noted that although the H3.3A and H3.3B proteins are identical, their nucleotide coding sequences and flanking portions differ. They reported that H3.3a was basally expressed in mouse testis, whereas H3.3b was expressed in a stage-specific manner. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9188772" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using Northern blot analysis, <a href="#9" class="mim-tip-reference" title="Frank, D., Doenecke, D., Albig, W. <strong>Differential expression of human replacement and cell cycle dependent H3 histone genes.</strong> Gene 312: 135-143, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12909349/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12909349</a>] [<a href="https://doi.org/10.1016/s0378-1119(03)00609-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12909349">Frank et al. (2003)</a> assayed for expression of the replacement histones H3.3A and H3.3B and the cell cycle-dependent histone H3/m (HIST2H3C; <a href="/entry/142780">142780</a>) in human tissues and cell lines. All 6 cell lines expressed H3.3A, H3.3B, and H3/m at high levels. Conversely, fetal liver predominantly expressed H3/m, likely due to its rapid cell growth, whereas adult liver, kidney, and heart predominantly expressed H3.3A and H3.3B. The H3.3A transcript was detected at 1.0 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12909349" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#21" class="mim-tip-reference" title="Wells, D., Kedes, L. <strong>Structure of a human histone cDNA: evidence that basally expressed histone genes have intervening sequences and encode polyadenylated mRNAs.</strong> Proc. Nat. Acad. Sci. 82: 2834-2838, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2859593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2859593</a>] [<a href="https://doi.org/10.1073/pnas.82.9.2834" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2859593">Wells and Kedes (1985)</a> determined that the 5-prime UTR of the H3F3A gene is GC rich (75%). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2859593" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Wells, D., Hoffman, D., Kedes, L. <strong>Unusual structure, evolutionary conservation of non-coding sequences and numerous pseudogenes characterize the H3.3 histone multigene family.</strong> Nucleic Acids Res. 15: 2871-2889, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3031613/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3031613</a>] [<a href="https://doi.org/10.1093/nar/15.7.2871" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3031613">Wells et al. (1987)</a> determined that the H3F3A gene contains 4 exons and spans 8.8 kb. The first exon is noncoding. The 5-prime end contains noncanonical TATA and CCAAT boxes and an SP1 (<a href="/entry/189906">189906</a>)-binding GC box. The 3-prime end contains 2 potential polyadenylation signals and is highly conserved, sharing 85% identity with the chicken ortholog. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3031613" 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 analysis of a somatic cell hybrid panel and by inclusion within a YAC from that region, <a href="#15" class="mim-tip-reference" title="Lin, X., Wells, D. E. <strong>Localization of the human H3F3A histone gene to 1q41, outside of the normal histone gene clusters.</strong> Genomics 46: 526-528, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9441765/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9441765</a>] [<a href="https://doi.org/10.1006/geno.1997.5037" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9441765">Lin and Wells (1997)</a> mapped the H3F3A gene to chromosome 1q41. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9441765" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Stumpf, A. M. <strong>Personal Communication.</strong> Baltimore, Md. 02/01/2022."None>Stumpf (2022)</a> mapped the H3F3A gene to chromosome 1q42.12 based on an alignment of the H3F3A sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=BC029405" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">BC029405</a>) with the genomic sequence (GRCh38).</p>
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<p>See HIST1H3A (<a href="/entry/602810">602810</a>) for functional information on the H3 histone family.</p><p><strong><em>H3.3 Histone</em></strong></p><p>
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<a href="#11" class="mim-tip-reference" title="Hake, S. B., Garcia, B. A., Duncan, E. M., Kauer, M., Dellaire, G., Shabanowitz, J., Bazett-Jones, D. P., Allis, C. D., Hunt, D. F. <strong>Expression patterns and post-translational modifications associated with mammalian histone H3 variants.</strong> J. Biol. Chem. 281: 559-568, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16267050/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16267050</a>] [<a href="https://doi.org/10.1074/jbc.M509266200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16267050">Hake et al. (2006)</a> noted that most studies on expression or posttranslational modifications of H3 histones do not differentiate between the H3.1 (see <a href="/entry/602810">602810</a>), H3.2 (HIST2H3C; <a href="/entry/142780">142780</a>), and H3.3 proteins, in part due to their high degree of amino acid identity. By quantitative PCR of 5 human cell lines, they found that the 9 H3.1 genes, 1 H3.2 gene, and 2 H3.3 genes examined were expressed in a cell line-specific manner. All 3 types of H3 genes were highly expressed during S phase in human cell lines, whereas the H3.3 genes were also highly expressed outside of S phase, consistent with their status as replication-independent genes. Using a combination of isotopic labeling and quantitative tandem mass spectrometry, <a href="#11" class="mim-tip-reference" title="Hake, S. B., Garcia, B. A., Duncan, E. M., Kauer, M., Dellaire, G., Shabanowitz, J., Bazett-Jones, D. P., Allis, C. D., Hunt, D. F. <strong>Expression patterns and post-translational modifications associated with mammalian histone H3 variants.</strong> J. Biol. Chem. 281: 559-568, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16267050/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16267050</a>] [<a href="https://doi.org/10.1074/jbc.M509266200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16267050">Hake et al. (2006)</a> showed that the H3.1, H3.2, and H3.3 proteins differed in their posttranslational modifications. H3.1 was enriched in marks associated with both gene activation and gene silencing, H3.2 was enriched in repressive marks associated with gene silencing and the formation of facultative heterochromatin, and H3.3 was enriched in marks associated with transcriptional activation. <a href="#11" class="mim-tip-reference" title="Hake, S. B., Garcia, B. A., Duncan, E. M., Kauer, M., Dellaire, G., Shabanowitz, J., Bazett-Jones, D. P., Allis, C. D., Hunt, D. F. <strong>Expression patterns and post-translational modifications associated with mammalian histone H3 variants.</strong> J. Biol. Chem. 281: 559-568, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16267050/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16267050</a>] [<a href="https://doi.org/10.1074/jbc.M509266200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16267050">Hake et al. (2006)</a> concluded that H3.1, H3.2, and H3.3 likely have unique functions and should not be treated as equivalent proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16267050" 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="#13" class="mim-tip-reference" title="Jin, C., Zang, C., Wei, G., Cui, K., Peng, W., Zhao, K., Felsenfeld, G. <strong>H3.3/H2A.Z double variant-containing nucleosomes mark 'nucleosome-free regions' of active promoters and other regulatory regions.</strong> Nature Genet. 41: 941-945, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19633671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19633671</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19633671[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.409" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19633671">Jin et al. (2009)</a> characterized the genomewide distribution of nucleosome core particles containing H3.3 and/or H2A.Z (H2AFZ; <a href="/entry/142763">142763</a>) in HeLa cells. They found that highly labile particles containing both H3.3 and H2A.Z were enriched at active promoters, enhancers, and insulator regions. Nucleosomes containing H3.3, but not H2A.Z, were also relatively unstable and were detected along the transcribed region of genes and at transcriptional stop sites. <a href="#13" class="mim-tip-reference" title="Jin, C., Zang, C., Wei, G., Cui, K., Peng, W., Zhao, K., Felsenfeld, G. <strong>H3.3/H2A.Z double variant-containing nucleosomes mark 'nucleosome-free regions' of active promoters and other regulatory regions.</strong> Nature Genet. 41: 941-945, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19633671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19633671</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19633671[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.409" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19633671">Jin et al. (2009)</a> suggested that unstable particles containing both H3.3 and H2A.Z may serve as place holders that are easily displaced by transcription factors. They proposed that unstable particles containing only H3.3 along the transcribed portions of genes may accommodate the passage of RNA polymerase. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19633671" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#24" class="mim-tip-reference" title="Xu, M., Long, C., Chen, X., Huang, C., Chen, S., Zhu, B. <strong>Partitioning of histone H3-H4 tetramers during DNA replication-dependent chromatin assembly.</strong> Science 328: 94-98, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20360108/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20360108</a>] [<a href="https://doi.org/10.1126/science.1178994" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20360108">Xu et al. (2010)</a> reported that significant amounts of histone H3.3-H4 (see <a href="/entry/602822">602822</a>) tetramers split in vivo, whereas most H3.1 (see <a href="/entry/602810">602810</a>)-H4 tetramers remain intact during mitotic division. Inhibiting DNA replication-dependent deposition greatly reduced the level of splitting events, which suggested that (i) the replication-independent H3.3 deposition pathway proceeds largely by cooperatively incorporating 2 new H3.3-H4 dimers, and (ii) the majority of splitting events occur during replication-dependent deposition. <a href="#24" class="mim-tip-reference" title="Xu, M., Long, C., Chen, X., Huang, C., Chen, S., Zhu, B. <strong>Partitioning of histone H3-H4 tetramers during DNA replication-dependent chromatin assembly.</strong> Science 328: 94-98, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20360108/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20360108</a>] [<a href="https://doi.org/10.1126/science.1178994" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20360108">Xu et al. (2010)</a> concluded that 'silent' histone modifications within large heterochromatic regions are maintained by copying modifications from neighboring preexisting histones without the need for H3-H4 splitting events. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20360108" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#19" class="mim-tip-reference" title="Talbert, P. B., Henikoff, S. <strong>Histone variants--ancient wrap artists of the epigenome.</strong> Nature Rev. Molec. Cell Biol. 11: 264-275, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20197778/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20197778</a>] [<a href="https://doi.org/10.1038/nrm2861" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20197778">Talbert and Henikoff (2010)</a> reviewed the assembly of canonical nucleosomes, which is thought to begin with a tetramer of 2 H3 molecules and 2 H4 molecules held together by strong bonds between the H3 molecules. H3.1 is the major canonical H3 assembled into chromatin by the histone chaperone CAF1 (see <a href="/entry/601246">601246</a>) complex during DNA replication and repair. The replacement histone H3.3 is assembled by the histone regulator A (HIRA; <a href="/entry/600237">600237</a>) complex independently of DNA synthesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20197778" 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 knockdown analysis, <a href="#3" class="mim-tip-reference" title="Banaszynski, L. A., Wen, D., Dewell, S., Whitcomb, S. J., Lin, M., Diaz, N., Elsasser, S. J., Chapgier, A., Goldberg, A. D., Canaani, E., Rafii, S., Zheng, D., Allis, C. D. <strong>Hira-dependent histone H3.3 deposition facilitates PRC2 recruitment at developmental loci in ES cells.</strong> Cell 155: 107-120, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24074864/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24074864</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24074864[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.cell.2013.08.061" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24074864">Banaszynski et al. (2013)</a> showed that depletion of H3.3 (i.e., both H3f3A and H3f3b) in mouse embryonic stem cells (ESCs) resulted in globally reduced chromatin dynamics at promoters and reduced H3K27me3 enrichment at promoters of developmentally regulated bivalent genes. Reduction of H3K27me3 enrichment at bivalent genes upregulated expression of transcription factors essential for trophectoderm specification in ESCs, likely due to perturbation of the balance between activation-associated H3K4me3 and repression-associated H3K27me3 on the promoters. H3.3-depleted ESCs could differentiate toward the typically restricted trophectoderm lineage, as H3.3-dependent reduction of H3K27me3 enrichment at developmentally regulated promoters resulted in gene misregulation upon differentiation rather than deregulation in the pluripotent state. H3.3 facilitated the proper chromatin environment for occupancy of the Polycomb repressive complex-2 (PRC2; see <a href="/entry/301036">301036</a>) at its target regions and/or for PRC2 activity toward H3, regardless of H3 isoform. Consequently, H3.3 depletion-induced reduction of H3K27me3 levels reduced PRC2 enrichment and activity at promoters of bivalent genes in ESCs. Deposition of H3.3 at promoters of developmentally regulated genes to establish a bivalent chromatin landscape in ESCs was dependent on Hira. Hira colocalized with promoter-proximal RNA polymerase II (see <a href="/entry/180660">180660</a>) and PRC2 at promoters of developmentally regulated genes in ESCs, and Hira -/- ESCs recapitulated the loss of H3K27me3 and PRC2 at bivalent promoters observed in H3.3-depleted ESCs. Recruitment of PRC2 to promoters was H3.3 dependent, as Hira interacted with PRC2, and the interaction required H3.3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24074864" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Elsasser, S. J., Noh, K.-M., Diaz, N., Allis, C. D., Banaszynski, L. A. <strong>Histone H3.3 is required for endogenous retroviral element silencing in embryonic stem cells.</strong> Nature 522: 240-244, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25938714/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25938714</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25938714[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/nature14345" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25938714">Elsasser et al. (2015)</a> showed that the replacement histone variant H3.3 is enriched at class I and class II endogenous retroviral elements (ERVs), notably those of the early transposon/MusD family and intracisternal A-type particles. Deposition at a subset of these elements is dependent on the H3.3 chaperone complex containing ATRX (<a href="/entry/300032">300032</a>) and DAXX (<a href="/entry/603186">603186</a>). <a href="#8" class="mim-tip-reference" title="Elsasser, S. J., Noh, K.-M., Diaz, N., Allis, C. D., Banaszynski, L. A. <strong>Histone H3.3 is required for endogenous retroviral element silencing in embryonic stem cells.</strong> Nature 522: 240-244, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25938714/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25938714</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25938714[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/nature14345" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25938714">Elsasser et al. (2015)</a> demonstrated that recruitment of DAXX, H3.3, and KAP1 (TRIM28; <a href="/entry/601742">601742</a>) to ERVs is codependent and occurs upstream of ESET (SETDB1; <a href="/entry/604396">604396</a>), linking H3.3 to ERV-associated H3K9me3. Importantly, H3K9me3 is reduced at ERVs upon H3.3 deletion, resulting in derepression and dysregulation of adjacent, endogenous genes, along with increased retrotransposition of intracisternal A-type particles. <a href="#8" class="mim-tip-reference" title="Elsasser, S. J., Noh, K.-M., Diaz, N., Allis, C. D., Banaszynski, L. A. <strong>Histone H3.3 is required for endogenous retroviral element silencing in embryonic stem cells.</strong> Nature 522: 240-244, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25938714/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25938714</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25938714[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/nature14345" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25938714">Elsasser et al. (2015)</a> concluded that their study identifies a unique heterochromatin state marked by the presence of both H3.3 and H3K9me3, and establishes an important role for H3.3 in control of ERV retrotransposition in embryonic stem cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25938714" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The N terminus of H3.3 contains a unique serine, ser31, that is absent in canonical H3.1 and H3.2. <a href="#2" class="mim-tip-reference" title="Armache, A., Yang, S., Martinez de Paz, A., Robbins, L. E., Durmaz, C., Cheong, J. Q., Ravishankar, A., Daman, A. W., Ahimovic, D. J., Klevorn, T., Yue, Y., Arslan, T., and 13 others. <strong>Histone H3.3 phosphorylation amplifies stimulation-induced transcription.</strong> Nature 583: 852-857, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32699416/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32699416</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32699416[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/s41586-020-2533-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32699416">Armache et al. (2020)</a> showed that ser31 was phosphorylated in a stimulation-dependent manner along rapidly induced genes in mouse macrophages. This selective mark of stimulation-responsive genes directly engaged Setd2 (<a href="/entry/612778">612778</a>), a component of the active transcription machinery, and ejected the elongation corepressor Zmynd11 (<a href="/entry/608668">608668</a>). <a href="#2" class="mim-tip-reference" title="Armache, A., Yang, S., Martinez de Paz, A., Robbins, L. E., Durmaz, C., Cheong, J. Q., Ravishankar, A., Daman, A. W., Ahimovic, D. J., Klevorn, T., Yue, Y., Arslan, T., and 13 others. <strong>Histone H3.3 phosphorylation amplifies stimulation-induced transcription.</strong> Nature 583: 852-857, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32699416/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32699416</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32699416[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/s41586-020-2533-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32699416">Armache et al. (2020)</a> proposed that features of H3.3 at stimulation-induced genes, including phosphorylated ser31, provide preferential access to the transcription apparatus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32699416" 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 href="#7" class="mim-tip-reference" title="Elsasser, S. J., Huang, H., Lewis, P. W., Chin, J. W., Allis, C. D., Patel, D. J. <strong>DAXX envelops a histone H3.3-H4 dimer for H3.3-specific recognition.</strong> Nature 491: 560-565, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23075851/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23075851</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23075851[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/nature11608" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23075851">Elsasser et al. (2012)</a> reported the crystal structures of the DAXX (<a href="/entry/603186">603186</a>) histone-binding domain with a histone H3.3-H4 (see <a href="/entry/602822">602822</a>) dimer, including mutants within DAXX and H3.3, together with in vitro and in vivo functional studies that elucidated the principles underlying H3.3 recognition specificity. Occupying 40% of the histone surface-accessible area, DAXX wraps around the H3.3-H4 dimer, with complex formation accompanied by structural transitions in the H3.3-H4 histone fold. DAXX uses an extended alpha-helical conformation to compete with major interhistone, DNA, and ASF1 interaction sites. <a href="#7" class="mim-tip-reference" title="Elsasser, S. J., Huang, H., Lewis, P. W., Chin, J. W., Allis, C. D., Patel, D. J. <strong>DAXX envelops a histone H3.3-H4 dimer for H3.3-specific recognition.</strong> Nature 491: 560-565, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23075851/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23075851</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23075851[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/nature11608" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23075851">Elsasser et al. (2012)</a> concluded that their structural studies identified recognition elements that read out H3.3-specific residues, and functional studies addressed the contribution of gly90 in H3.3 and glu225 in DAXX to chaperone-mediated H3.3 variant recognition specificity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23075851" 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 href="#17" class="mim-tip-reference" title="Schwartzentruber, J., Korshunov, A, Liu, X.-Y., Jones, D. T. W., Pfaff, E., Jacob, K., Sturm, D., Fontebasso, A. M., Quang, D.-A. K., Tonjes, M., Hovestadt, V., Albrecht, S., and 50 others. <strong>Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma.</strong> Nature 482: 226-231, 2012. Note: Erratum: Nature 484: 130 only, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22286061/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22286061</a>] [<a href="https://doi.org/10.1038/nature10833" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22286061">Schwartzentruber et al. (2012)</a> sequenced the exomes of 48 pediatric glioblastoma (<a href="/entry/137800">137800</a>) samples. Somatic mutations in the H3.3-ATRX (<a href="/entry/300032">300032</a>)-DAXX (<a href="/entry/603186">603186</a>) chromatin remodeling pathway were identified in 44% of tumors (21 of 48). Recurrent mutations in H3F3A, which encodes the replication-independent histone-3 variant H3.3, were observed in 31% of tumors, and led to amino acid substitutions at 2 critical positions within the histone tail (K27M, G34R/G34V) involved in key regulatory posttranslational modifications. Mutations in ATRX and DAXX, encoding 2 subunits of a chromatin remodeling complex required for H3.3 incorporation at pericentric heterochromatin and telomeres, were identified in 31% of samples overall, and in 100% of tumors harboring a G34R or G34V H3.3 mutation. Somatic TP53 (<a href="/entry/191170">191170</a>) mutations were identified in 54% of all cases, and in 86% of samples with H3F3A and/or ATRX mutations. Screening of a large cohort of gliomas of various grades and histologies (n = 784) showed H3F3A mutations to be specific to glioblastoma multiforme and highly prevalent in children and young adults. Furthermore, the presence of H3F3A/ATRX-DAXX/TP53 mutations was strongly associated with alternative lengthening of telomeres and specific gene expression profiles. <a href="#17" class="mim-tip-reference" title="Schwartzentruber, J., Korshunov, A, Liu, X.-Y., Jones, D. T. W., Pfaff, E., Jacob, K., Sturm, D., Fontebasso, A. M., Quang, D.-A. K., Tonjes, M., Hovestadt, V., Albrecht, S., and 50 others. <strong>Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma.</strong> Nature 482: 226-231, 2012. Note: Erratum: Nature 484: 130 only, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22286061/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22286061</a>] [<a href="https://doi.org/10.1038/nature10833" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22286061">Schwartzentruber et al. (2012)</a> stated that this was the first report to highlight recurrent mutations in a regulatory histone in humans, and that their data suggested that defects of the chromatin architecture underlie pediatric and young adult glioblastoma multiforme pathogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22286061" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#23" class="mim-tip-reference" title="Wu, G., Broniscer, A., McEachron, T. A., Lu, C., Paugh, B. S., Becksfort, J., Qu, C., Ding, L., Huether, R., Parker, M., Zhang, J., Gajjar, A., and 9 others. <strong>Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas.</strong> Nature Genet. 44: 251-253, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22286216/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22286216</a>] [<a href="https://doi.org/10.1038/ng.1102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22286216">Wu et al. (2012)</a> reported that a K27M mutation occurring in either H3F3A or HIST1H3B (<a href="/entry/602819">602819</a>) was observed in 78% of diffuse intrinsic pontine gliomas (DIPGs) and 22% of non-brain-stem gliomas. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22286216" 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="#14" class="mim-tip-reference" title="Lewis, P. W., Muller, M. M., Koletsky, M. S., Cordero, F., Lin, S., Banaszynski, L. A., Garcia, B. A., Muir, T. W., Becher, O. J., Allis, C. D. <strong>Inhibition of PRC2 activity by a gain-of-function H3 mutation found in pediatric glioblastoma.</strong> Science 340: 857-861, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23539183/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23539183</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23539183[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1232245" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23539183">Lewis et al. (2013)</a> reported that human DIPGs containing the K27M mutation in either histone H3.3 (H3F3A) or H3.1 (HIST1H3B) display significantly lower overall amounts of H3 with trimethylated lysine-27 (H3K27me3) and that histone H3K27M transgenes are sufficient to reduce the amounts of H3K27me3 in vitro and in vivo. <a href="#14" class="mim-tip-reference" title="Lewis, P. W., Muller, M. M., Koletsky, M. S., Cordero, F., Lin, S., Banaszynski, L. A., Garcia, B. A., Muir, T. W., Becher, O. J., Allis, C. D. <strong>Inhibition of PRC2 activity by a gain-of-function H3 mutation found in pediatric glioblastoma.</strong> Science 340: 857-861, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23539183/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23539183</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23539183[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1232245" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23539183">Lewis et al. (2013)</a> found that H3K27M inhibits the enzymatic activity of the Polycomb repressive complex-2 (PRC2) through interaction with the EZH2 (<a href="/entry/601573">601573</a>) subunit. In addition, transgenes containing lysine-to-methionine substitutions at other known methylated lysines (H3K9 and H3K36) are sufficient to cause specific reduction in methylation through inhibition of SET domain enzymes. <a href="#14" class="mim-tip-reference" title="Lewis, P. W., Muller, M. M., Koletsky, M. S., Cordero, F., Lin, S., Banaszynski, L. A., Garcia, B. A., Muir, T. W., Becher, O. J., Allis, C. D. <strong>Inhibition of PRC2 activity by a gain-of-function H3 mutation found in pediatric glioblastoma.</strong> Science 340: 857-861, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23539183/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23539183</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23539183[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1232245" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23539183">Lewis et al. (2013)</a> proposed that K-to-M substitutions may represent a mechanism to alter epigenetic states in a variety of pathologies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23539183" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Behjati, S., Tarpey, P. S., Presneau, N., Scheipl, S., Pillay, N., Van Loo, P., Wedge, D. C., Cooke, S. L., Gundem, G., Davies, H., Nik-Zainal, S., Martin, S., and 17 others. <strong>Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone.</strong> Nature Genet. 45: 1479-1482, 2013. Note: Erratum: Nature Genet. 46: 316 only, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24162739/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24162739</a>] [<a href="https://doi.org/10.1038/ng.2814" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24162739">Behjati et al. (2013)</a> reported exquisite tumor type specificity for different histone H3.3 driver alterations. In 73 of 77 cases (95%) of chondroblastoma, <a href="#4" class="mim-tip-reference" title="Behjati, S., Tarpey, P. S., Presneau, N., Scheipl, S., Pillay, N., Van Loo, P., Wedge, D. C., Cooke, S. L., Gundem, G., Davies, H., Nik-Zainal, S., Martin, S., and 17 others. <strong>Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone.</strong> Nature Genet. 45: 1479-1482, 2013. Note: Erratum: Nature Genet. 46: 316 only, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24162739/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24162739</a>] [<a href="https://doi.org/10.1038/ng.2814" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24162739">Behjati et al. (2013)</a> found K36M alterations predominantly encoded by H3F3B (<a href="/entry/601058">601058</a>), which is 1 of 2 genes for histone H3.3. In contrast, in 92% (49 of 53) of giant cell tumors of bone, <a href="#4" class="mim-tip-reference" title="Behjati, S., Tarpey, P. S., Presneau, N., Scheipl, S., Pillay, N., Van Loo, P., Wedge, D. C., Cooke, S. L., Gundem, G., Davies, H., Nik-Zainal, S., Martin, S., and 17 others. <strong>Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone.</strong> Nature Genet. 45: 1479-1482, 2013. Note: Erratum: Nature Genet. 46: 316 only, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24162739/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24162739</a>] [<a href="https://doi.org/10.1038/ng.2814" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24162739">Behjati et al. (2013)</a> found histone H3.3 alterations exclusively in H3F3A, leading to G34W or, in 1 case, G34L alterations. The mutations were restricted to the stromal cell population and were not detected in osteoclasts or their precursors. In the context of previously reported H3F3A mutations encoding K27M and G34R or G34V alterations in childhood brain tumors, a picture of tumor type specificity for histone H3.3 driver alterations emerged, indicating that histone H3.3 residues, mutations, and genes have distinct functions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24162739" 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>Diffuse intrinsic pediatric gliomas (DIPGs) are rare, highly aggressive brainstem tumors. Over 70% of DIPGs harbor somatic mutations in the H3F3A gene that result in a lys27-to-met (K27M) substitution. Tumors that are positive for the mutation are associated with a poor prognosis and diminished survival. <a href="#10" class="mim-tip-reference" title="Funato, K., Major, T., Lewis, P. W., Allis, C. D., Tabar, V. <strong>Use of human embryonic stem cells to model pediatric gliomas with H3.3K27M histone mutation.</strong> Science 346: 1529-1533, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25525250/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25525250</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25525250[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1253799" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25525250">Funato et al. (2014)</a> used a human embryonic stem cell system to model this tumor, and showed that H3.3K27M expression synergizes with loss of p53 (<a href="/entry/191170">191170</a>) and activation of PDGFRA (<a href="/entry/173490">173490</a>) in neural progenitor cells derived from human embryonic stem cells, resulting in neoplastic transformation. Genomewide analyses indicated a resetting of the transformed precursors to a developmentally more primitive stem cell state, with evidence of major modifications of histone marks at several master regulator genes. Drug screening assays identified a compound targeting the protein menin (<a href="/entry/613733">613733</a>) as an inhibitor of tumor cell growth in vitro and in mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25525250" 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>Bryant-Li-Bhoj Neurodevelopmental Syndrome 1</em></strong></p><p>
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In 33 unrelated patients with Bryant-Li-Bhoj neurodevelopmental syndrome-1 (BRYLIB1; <a href="/entry/619720">619720</a>), <a href="#5" class="mim-tip-reference" title="Bryant, L., Li, D., Cox, S. G., Marchione, D., Joiner, E. F., Wilson, K., Janssen, K., Lee, P., March, M. E., Nair, D., Sherr, E., Fregeau, B., and 119 others. <strong>Histone H3.3 beyond cancer: germline mutations in histone 3 family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients.</strong> Sci. Adv. 6: eabc9207, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33268356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33268356</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33268356[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/sciadv.abc9207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33268356">Bryant et al. (2020)</a> identified de novo heterozygous missense mutations in the H3F3A gene (see, e.g., <a href="#0001">601128.0001</a>-<a href="#0005">601128.0005</a>). The mutations, which were found by whole-exome or genome sequencing, occurred throughout the gene. All but 1 were absent from the gnomAD database. In vitro studies of lymphoblasts or fibroblasts derived from a subset of patients showed that the distribution of posttranslational modification (PTM) histone abundances was similar to controls. The overall histone PTM variation was slightly increased in controls compared to patients. Nonetheless, some histone PTMs were altered in patients compared to controls. The findings suggested that mutant histones can be incorporated into the nucleosome and cause local deregulation of the chromatin state with modest alterations in the control of histone modification. This could affect multiple histone functions, including gene expression, chromatin stability, DNA damage repair, and differentiation. RNA sequencing of a subset of pooled patient cells showed upregulation of genes involved in mitosis, and in vitro studies of pooled patient fibroblast lines showed increased cellular proliferation compared to controls; viability of patient cells was similar to controls. In silico molecular modeling of the mutations suggested 3 broad scenarios for the variants' impact: disruption of H3.3 DNA binding; disrupted formation of the histone octamer or binding with other histones; and disruption of histone-protein binding to chaperones or other interacting proteins. There were no genotype/phenotype correlations. None of the patients developed cancer. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33268356" 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 6 unrelated patients with BRYLIB1, <a href="#16" class="mim-tip-reference" title="Okur, V., Chen, Z., Vossaert, L., Peacock, S., Rosenfeld, J., Zhao, L., Du, H., Calamaro, E., Gerard, A., Zhao, S., Kelsay, J., Lahr, A., and 26 others. <strong>De novo variants in H3-3A and H3-3B are associated with neurodevelopmental delay, dysmorphic features, and structural brain abnormalities.</strong> NPJ Genom. Med. 6: 104, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34876591/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34876591</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34876591[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/s41525-021-00268-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34876591">Okur et al. (2021)</a> identified 6 different de novo heterozygous missense mutations at highly conserved residues in the H3F3A gene (see, e.g., <a href="#0003">601128.0003</a>; <a href="#0004">601128.0004</a>; <a href="#0006">601128.0006</a>-<a href="#0007">601128.0007</a>). The mutations, which were found by exome sequencing, were absent from the gnomAD database. Expression of a subset of variants in HEK293 cells showed that some resulted in decreased protein levels, whereas 1 (R41C; <a href="#0006">601128.0006</a>) increased protein levels compared to controls. Additional functional studies of some of the variants showed that 1 (R129H; <a href="#0007">601128.0007</a>) had a significantly stronger interaction with DAXX (<a href="/entry/603186">603186</a>) compared to controls, which might lead to aberrant transcription. The mutant proteins localized normally to the nucleus. Molecular modeling suggested that some, but not all, mutations might alter the PTMs of histone H3.3. The possible molecular pathomechanism of other mutations was unclear. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34876591" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#12" class="mim-tip-reference" title="Jang, C.-W., Shibata, Y., Starmer, J., Yee, D., Magnuson, T. <strong>Histone H3.3 maintains genome integrity during mammalian development.</strong> Genes Dev. 29: 1377-1392, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26159997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26159997</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26159997[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.264150.115" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26159997">Jang et al. (2015)</a> reported that deletion of H3f3a or H3f3b in mice had no apparent deleterious impact on phenotype or fertility. However, knockout of both genes (H3.3 DKO) led to developmental retardation and embryonic lethality. H3.3 DKO embryos showed reduced cell proliferation and increased cell death. Embryonic stem cells from H3.3 DKO mice had mitotic defects. Growth retardation could be rescued by deletion of p53. RNA sequencing analysis revealed that p53 -/- H3.3 DKO embryos had only limited changes to the transcriptome. H3.3 DKO mouse embryonic fibroblasts lacking p53 proliferated but showed mitotic abnormalities associated with defects in chromosomal heterochromatic structures at telomeres, centromeres, and pericentromeric regions, as well as genome instability. Karyotypic abnormalities and DNA damage in H3.3 DKO mice led to p53 pathway activation. <a href="#12" class="mim-tip-reference" title="Jang, C.-W., Shibata, Y., Starmer, J., Yee, D., Magnuson, T. <strong>Histone H3.3 maintains genome integrity during mammalian development.</strong> Genes Dev. 29: 1377-1392, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26159997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26159997</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26159997[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.264150.115" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26159997">Jang et al. (2015)</a> concluded that H3.3 supports chromosomal heterochromatic structures, thus maintaining genome integrity during mammalian development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26159997" 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="Bryant, L., Li, D., Cox, S. G., Marchione, D., Joiner, E. F., Wilson, K., Janssen, K., Lee, P., March, M. E., Nair, D., Sherr, E., Fregeau, B., and 119 others. <strong>Histone H3.3 beyond cancer: germline mutations in histone 3 family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients.</strong> Sci. Adv. 6: eabc9207, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33268356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33268356</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33268356[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/sciadv.abc9207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33268356">Bryant et al. (2020)</a> noted that zebrafish with a dominant D123N mutation in the h3f3a gene developed craniofacial abnormalities. Homozygous knockdown of the h3f3a gene resulted in a loss of neural crest-derived jaw cartilages. There was also a partial reduction in Foxd3 (<a href="/entry/611539">611539</a>)-derived cranial glia, melanocytes, and xanthophores; those injected with dominant-negative h3f3a showed a further reduction in these cell types. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33268356" 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">rs2102735576 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2102735576;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=rs2102735576" 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=rs2102735576" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 2 unrelated children (patients 4 and 5) with Bryant-Li-Bhoj neurodevelopmental syndrome-1 (BRYLIB1; <a href="/entry/619720">619720</a>), <a href="#5" class="mim-tip-reference" title="Bryant, L., Li, D., Cox, S. G., Marchione, D., Joiner, E. F., Wilson, K., Janssen, K., Lee, P., March, M. E., Nair, D., Sherr, E., Fregeau, B., and 119 others. <strong>Histone H3.3 beyond cancer: germline mutations in histone 3 family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients.</strong> Sci. Adv. 6: eabc9207, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33268356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33268356</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33268356[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/sciadv.abc9207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33268356">Bryant et al. (2020)</a> identified a de novo heterozygous c.52A-G transition (c.52A-G, NM_002107.4) in the H3F3A gene, resulting in an arg18-to-gly (R18G) substitution. The mutation, which was found by exome sequencing, was not present in the gnomAD database. The authors noted that this mutation would be described as ARG17GLY (R17G) according to standard histone nomenclature, which omits numbering the initiator methionine. In vitro studies of pooled patient cells showed some evidence of dysregulated histone posttranslational modifications as well as enhanced proliferation. Both patients had global developmental delay with late walking, absent speech, hypotonia, and dysmorphic facial features. One had controlled seizures and the other was tube-fed for a short time. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33268356" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0002 BRYANT-LI-BHOJ NEURODEVELOPMENTAL SYNDROME 1</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">rs1657901999 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1657901999;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=rs1657901999" 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=rs1657901999" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 4 unrelated patients (patients 11-14) with Bryant-Li-Bhoj neurodevelopmental syndrome-1 (BRYLIB1; <a href="/entry/619720">619720</a>), <a href="#5" class="mim-tip-reference" title="Bryant, L., Li, D., Cox, S. G., Marchione, D., Joiner, E. F., Wilson, K., Janssen, K., Lee, P., March, M. E., Nair, D., Sherr, E., Fregeau, B., and 119 others. <strong>Histone H3.3 beyond cancer: germline mutations in histone 3 family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients.</strong> Sci. Adv. 6: eabc9207, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33268356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33268356</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33268356[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/sciadv.abc9207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33268356">Bryant et al. (2020)</a> identified a de novo heterozygous c.137C-T transition (c.137C-T, NM_002107.4) in the H3F3A gene, resulting in a thr46-to-ile (T46I) substitution. The mutation, which was found by exome sequencing, was not present in the gnomAD database. The authors noted that this mutation would be described as THR45ILE (T45I) according to standard histone nomenclature, which omits numbering the initiator methionine. Analysis of pooled patient cells showed some evidence of dysregulated histone posttranslational modifications. In vitro studies of pooled patient cells showed some evidence of dysregulated histone posttranslational modifications as well as enhanced proliferation. The patients had global developmental delay with late walking, poor or absent speech, hypotonia, and dysmorphic features. One patient had seizures. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33268356" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 BRYANT-LI-BHOJ NEURODEVELOPMENTAL SYNDROME 1</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">rs2102737050 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2102737050;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=rs2102737050" 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=rs2102737050" 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=RCV001541911 OR RCV001823779" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001541911, RCV001823779" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001541911...</a>
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<p>In an 8-year-old girl (patient 20) with Bryant-Li-Bhoj neurodevelopmental syndrome-1 (BRYLIB1; <a href="/entry/619720">619720</a>), <a href="#5" class="mim-tip-reference" title="Bryant, L., Li, D., Cox, S. G., Marchione, D., Joiner, E. F., Wilson, K., Janssen, K., Lee, P., March, M. E., Nair, D., Sherr, E., Fregeau, B., and 119 others. <strong>Histone H3.3 beyond cancer: germline mutations in histone 3 family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients.</strong> Sci. Adv. 6: eabc9207, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33268356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33268356</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33268356[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/sciadv.abc9207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33268356">Bryant et al. (2020)</a> identified a de novo heterozygous c.271G-C transversion (c.271G-C, NM_002107.4) in the H3F3A gene, resulting in a gly91-to-arg (G91R) substitution. The mutation, which was found by exome sequencing, was not present in the gnomAD database. The authors noted that this mutation would be described as GLY90ARG (G90R) according to standard histone nomenclature, which omits numbering the initiator methionine. Molecular modeling suggested that the mutation could disrupt chaperone binding. In vitro studies of pooled patient cells showed some evidence of dysregulated histone posttranslational modifications as well as enhanced proliferation. The patient had severe global developmental delay with inability to walk or speak. She also had progressive short stature, hypo/hypertonia, and dysmorphic facial features. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33268356" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 28-year-old female (patient 2) with BRYLIB1, <a href="#16" class="mim-tip-reference" title="Okur, V., Chen, Z., Vossaert, L., Peacock, S., Rosenfeld, J., Zhao, L., Du, H., Calamaro, E., Gerard, A., Zhao, S., Kelsay, J., Lahr, A., and 26 others. <strong>De novo variants in H3-3A and H3-3B are associated with neurodevelopmental delay, dysmorphic features, and structural brain abnormalities.</strong> NPJ Genom. Med. 6: 104, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34876591/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34876591</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34876591[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/s41525-021-00268-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34876591">Okur et al. (2021)</a> identified a de novo heterozygous G91R mutation in the H3F3A gene. The mutant protein localized normally to the nucleus and was expressed at normal levels. Molecular modeling suggested that the mutation would not have an effect on histone PTM. The patient had short stature, global developmental delay, microcephaly, hypotonia, hypertonia of the extremities, and seizures. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34876591" 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 BRYANT-LI-BHOJ NEURODEVELOPMENTAL SYNDROME 1</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">rs1576203003 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1576203003;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=rs1576203003" 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=rs1576203003" 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=RCV000851307 OR RCV001541913 OR RCV001823747 OR RCV004017756" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000851307, RCV001541913, RCV001823747, RCV004017756" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000851307...</a>
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<p>In an 18-month-old girl (patient 27) with Bryant-Li-Bhoj neurodevelopmental syndrome-1 (BRYLIB1; <a href="/entry/619720">619720</a>), <a href="#5" class="mim-tip-reference" title="Bryant, L., Li, D., Cox, S. G., Marchione, D., Joiner, E. F., Wilson, K., Janssen, K., Lee, P., March, M. E., Nair, D., Sherr, E., Fregeau, B., and 119 others. <strong>Histone H3.3 beyond cancer: germline mutations in histone 3 family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients.</strong> Sci. Adv. 6: eabc9207, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33268356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33268356</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33268356[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/sciadv.abc9207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33268356">Bryant et al. (2020)</a> identified a de novo heterozygous c.365C-T transition (c.365C-T, NM_002107.4) in the H3F3A gene, resulting in a pro122-to-leu (P122L) substitution. The mutation, which was found by exome sequencing, was not present in the gnomAD database. The authors noted that this mutation would be described as PRO121LEU (P121L) according to standard histone nomenclature, which omits numbering the initiator methionine. Functional studies of the variant and studies of patient cells were not performed. The patient had global developmental delay with inability to walk or speak, hypotonia, focal epilepsy, dysmorphic facial features, and delayed visual tracking. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33268356" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 13-year-old boy (patient 3) with BRYLIB1, <a href="#16" class="mim-tip-reference" title="Okur, V., Chen, Z., Vossaert, L., Peacock, S., Rosenfeld, J., Zhao, L., Du, H., Calamaro, E., Gerard, A., Zhao, S., Kelsay, J., Lahr, A., and 26 others. <strong>De novo variants in H3-3A and H3-3B are associated with neurodevelopmental delay, dysmorphic features, and structural brain abnormalities.</strong> NPJ Genom. Med. 6: 104, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34876591/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34876591</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34876591[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/s41525-021-00268-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34876591">Okur et al. (2021)</a> identified a de novo heterozygous P122L mutation in the H3F3A gene. The mutant protein localized normally to the nucleus and was expressed at normal levels. Additional functional studies of the variant were not performed, but molecular modeling suggested that the mutation would not affect histone PTM. The patient had short stature, global developmental delay, microcephaly, hypotonia, and seizures. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34876591" 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 BRYANT-LI-BHOJ NEURODEVELOPMENTAL SYNDROME 1</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">rs1276519904 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1276519904;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=rs1276519904" 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=rs1276519904" 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=RCV000624606 OR RCV000994267 OR RCV001823740 OR RCV004555590" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000624606, RCV000994267, RCV001823740, RCV004555590" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000624606...</a>
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<p>In 4 unrelated patients (patients 29-32) with Bryant-Li-Bhoj neurodevelopmental syndrome-1 (BRYLIB1; <a href="/entry/619720">619720</a>), <a href="#5" class="mim-tip-reference" title="Bryant, L., Li, D., Cox, S. G., Marchione, D., Joiner, E. F., Wilson, K., Janssen, K., Lee, P., March, M. E., Nair, D., Sherr, E., Fregeau, B., and 119 others. <strong>Histone H3.3 beyond cancer: germline mutations in histone 3 family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients.</strong> Sci. Adv. 6: eabc9207, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33268356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33268356</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33268356[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/sciadv.abc9207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33268356">Bryant et al. (2020)</a> identified a de novo heterozygous c.377A-G transition (c.377A-G, NM_002107.4) in the last exon of the H3F3A gene, resulting in a gln126-to-arg (Q126R) substitution. The mutation, which was found by genome sequencing, was not present in the gnomAD database. The authors noted that this mutation would be described as GLN125ARG (Q125R) according to standard histone nomenclature, which omits numbering the initiator methionine. In vitro functional studies of the variant and studies of patient cells were not performed, but molecular modeling predicted that it could disrupt assembly of the histone octomer by affecting intramonomer contacts. The patients had severe global developmental delay, hypotonia, seizures, dysmorphic features, and brain imaging abnormalities. One was tube-fed, and another died at 10 months of age. None achieved walking or language, including the oldest who was 15 years of age. Two patients showed neurologic regression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33268356" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 BRYANT-LI-BHOJ NEURODEVELOPMENTAL SYNDROME 1</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">rs2102735801 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2102735801;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=rs2102735801" 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=rs2102735801" 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=RCV001541909 OR RCV001823778" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001541909, RCV001823778" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001541909...</a>
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<p>In a patient with Bryant-Li-Bhoj neurodevelopmental syndrome-1 (BRYLIB1; <a href="/entry/619720">619720</a>), <a href="#16" class="mim-tip-reference" title="Okur, V., Chen, Z., Vossaert, L., Peacock, S., Rosenfeld, J., Zhao, L., Du, H., Calamaro, E., Gerard, A., Zhao, S., Kelsay, J., Lahr, A., and 26 others. <strong>De novo variants in H3-3A and H3-3B are associated with neurodevelopmental delay, dysmorphic features, and structural brain abnormalities.</strong> NPJ Genom. Med. 6: 104, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34876591/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34876591</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34876591[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/s41525-021-00268-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34876591">Okur et al. (2021)</a> identified a de novo heterozygous c.121C-T transition (c.121C-T, NM_002107.7) in the H3F3A gene, resulting in an arg41-to-cys (R41C) substitution at a conserved residue. The mutation was found by exome sequencing; it was not present in the gnomAD database. Expression of the mutation in HEK293 cells showed that it caused increased protein levels compared to controls. The mutant protein localized normally to the nucleus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34876591" 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">rs1658121882 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1658121882;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=rs1658121882" 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=rs1658121882" 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=RCV001541914 OR RCV001823780" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001541914, RCV001823780" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001541914...</a>
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<p>In a 4.5-year-old boy (patient 4) with Bryant-Li-Bhoj neurodevelopmental syndrome-1 (BRYLIB1; <a href="/entry/619720">619720</a>), <a href="#16" class="mim-tip-reference" title="Okur, V., Chen, Z., Vossaert, L., Peacock, S., Rosenfeld, J., Zhao, L., Du, H., Calamaro, E., Gerard, A., Zhao, S., Kelsay, J., Lahr, A., and 26 others. <strong>De novo variants in H3-3A and H3-3B are associated with neurodevelopmental delay, dysmorphic features, and structural brain abnormalities.</strong> NPJ Genom. Med. 6: 104, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34876591/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34876591</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34876591[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/s41525-021-00268-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34876591">Okur et al. (2021)</a> identified a de novo heterozygous c.386G-A transition (c.386G-A, NM_002107.7) in the H3F3A gene, resulting in an arg129-to-his (R129H) substitution at a conserved residue. The mutation was found by exome sequencing; it was not present in the gnomAD database. In vitro functional studies showed that the R129H mutant protein had a significantly stronger interaction with DAXX (<a href="/entry/603186">603186</a>) compared to controls, which might lead to aberrant transcription. The mutant protein localized normally to the nucleus. Molecular modeling suggested that the mutation would not alter the PTM of histone H3.3. The patient had short stature, global developmental delay, hypotonia, and dysmorphic features. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34876591" 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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Albig, W., Bramlage, B., Gruber, K., Klobeck, H.-G., Kunz, J., Doenecke, D.
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<strong>The human replacement histone H3.3B gene (H3F3B).</strong>
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Genomics 30: 264-272, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8586426/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8586426</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8586426" 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/10.1006/geno.1995.9878" target="_blank">Full Text</a>]
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Armache, A., Yang, S., Martinez de Paz, A., Robbins, L. E., Durmaz, C., Cheong, J. Q., Ravishankar, A., Daman, A. W., Ahimovic, D. J., Klevorn, T., Yue, Y., Arslan, T., and 13 others.
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<strong>Histone H3.3 phosphorylation amplifies stimulation-induced transcription.</strong>
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Nature 583: 852-857, 2020.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32699416/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32699416</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32699416[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=32699416" 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/s41586-020-2533-0" target="_blank">Full Text</a>]
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Banaszynski, L. A., Wen, D., Dewell, S., Whitcomb, S. J., Lin, M., Diaz, N., Elsasser, S. J., Chapgier, A., Goldberg, A. D., Canaani, E., Rafii, S., Zheng, D., Allis, C. D.
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<strong>Hira-dependent histone H3.3 deposition facilitates PRC2 recruitment at developmental loci in ES cells.</strong>
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Cell 155: 107-120, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24074864/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24074864</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24074864[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=24074864" 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.cell.2013.08.061" target="_blank">Full Text</a>]
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Behjati, S., Tarpey, P. S., Presneau, N., Scheipl, S., Pillay, N., Van Loo, P., Wedge, D. C., Cooke, S. L., Gundem, G., Davies, H., Nik-Zainal, S., Martin, S., and 17 others.
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<strong>Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone.</strong>
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Nature Genet. 45: 1479-1482, 2013. Note: Erratum: Nature Genet. 46: 316 only, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24162739/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24162739</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24162739" 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.2814" target="_blank">Full Text</a>]
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Bryant, L., Li, D., Cox, S. G., Marchione, D., Joiner, E. F., Wilson, K., Janssen, K., Lee, P., March, M. E., Nair, D., Sherr, E., Fregeau, B., and 119 others.
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<strong>Histone H3.3 beyond cancer: germline mutations in histone 3 family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients.</strong>
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Sci. Adv. 6: eabc9207, 2020.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33268356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33268356</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33268356[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=33268356" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/sciadv.abc9207" target="_blank">Full Text</a>]
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Chalmers, M., Wells, D.
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<strong>Extreme sequence conservation characterizes the rabbit H3.3A histone cDNA.</strong>
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Nucleic Acids Res. 18: 3075, 1990.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2349118/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2349118</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2349118" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/nar/18.10.3075" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Elsasser2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Elsasser, S. J., Huang, H., Lewis, P. W., Chin, J. W., Allis, C. D., Patel, D. J.
|
|
<strong>DAXX envelops a histone H3.3-H4 dimer for H3.3-specific recognition.</strong>
|
|
Nature 491: 560-565, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23075851/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23075851</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23075851[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=23075851" 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/nature11608" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Elsasser2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Elsasser, S. J., Noh, K.-M., Diaz, N., Allis, C. D., Banaszynski, L. A.
|
|
<strong>Histone H3.3 is required for endogenous retroviral element silencing in embryonic stem cells.</strong>
|
|
Nature 522: 240-244, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25938714/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25938714</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25938714[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=25938714" 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/nature14345" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Frank2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Frank, D., Doenecke, D., Albig, W.
|
|
<strong>Differential expression of human replacement and cell cycle dependent H3 histone genes.</strong>
|
|
Gene 312: 135-143, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12909349/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12909349</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12909349" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0378-1119(03)00609-7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Funato2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Funato, K., Major, T., Lewis, P. W., Allis, C. D., Tabar, V.
|
|
<strong>Use of human embryonic stem cells to model pediatric gliomas with H3.3K27M histone mutation.</strong>
|
|
Science 346: 1529-1533, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25525250/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25525250</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25525250[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=25525250" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1253799" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Hake2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hake, S. B., Garcia, B. A., Duncan, E. M., Kauer, M., Dellaire, G., Shabanowitz, J., Bazett-Jones, D. P., Allis, C. D., Hunt, D. F.
|
|
<strong>Expression patterns and post-translational modifications associated with mammalian histone H3 variants.</strong>
|
|
J. Biol. Chem. 281: 559-568, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16267050/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16267050</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16267050" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M509266200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Jang2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jang, C.-W., Shibata, Y., Starmer, J., Yee, D., Magnuson, T.
|
|
<strong>Histone H3.3 maintains genome integrity during mammalian development.</strong>
|
|
Genes Dev. 29: 1377-1392, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26159997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26159997</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26159997[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=26159997" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1101/gad.264150.115" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Jin2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jin, C., Zang, C., Wei, G., Cui, K., Peng, W., Zhao, K., Felsenfeld, G.
|
|
<strong>H3.3/H2A.Z double variant-containing nucleosomes mark 'nucleosome-free regions' of active promoters and other regulatory regions.</strong>
|
|
Nature Genet. 41: 941-945, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19633671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19633671</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19633671[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=19633671" 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.409" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Lewis2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lewis, P. W., Muller, M. M., Koletsky, M. S., Cordero, F., Lin, S., Banaszynski, L. A., Garcia, B. A., Muir, T. W., Becher, O. J., Allis, C. D.
|
|
<strong>Inhibition of PRC2 activity by a gain-of-function H3 mutation found in pediatric glioblastoma.</strong>
|
|
Science 340: 857-861, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23539183/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23539183</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23539183[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=23539183" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1232245" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Lin1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lin, X., Wells, D. E.
|
|
<strong>Localization of the human H3F3A histone gene to 1q41, outside of the normal histone gene clusters.</strong>
|
|
Genomics 46: 526-528, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9441765/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9441765</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9441765" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1997.5037" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Okur2021" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Okur, V., Chen, Z., Vossaert, L., Peacock, S., Rosenfeld, J., Zhao, L., Du, H., Calamaro, E., Gerard, A., Zhao, S., Kelsay, J., Lahr, A., and 26 others.
|
|
<strong>De novo variants in H3-3A and H3-3B are associated with neurodevelopmental delay, dysmorphic features, and structural brain abnormalities.</strong>
|
|
NPJ Genom. Med. 6: 104, 2021.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34876591/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34876591</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34876591[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=34876591" 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/s41525-021-00268-8" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Schwartzentruber2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schwartzentruber, J., Korshunov, A, Liu, X.-Y., Jones, D. T. W., Pfaff, E., Jacob, K., Sturm, D., Fontebasso, A. M., Quang, D.-A. K., Tonjes, M., Hovestadt, V., Albrecht, S., and 50 others.
|
|
<strong>Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma.</strong>
|
|
Nature 482: 226-231, 2012. Note: Erratum: Nature 484: 130 only, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22286061/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22286061</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22286061" 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/nature10833" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Stumpf2022" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Stumpf, A. M.
|
|
<strong>Personal Communication.</strong>
|
|
Baltimore, Md. 02/01/2022.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Talbert2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Talbert, P. B., Henikoff, S.
|
|
<strong>Histone variants--ancient wrap artists of the epigenome.</strong>
|
|
Nature Rev. Molec. Cell Biol. 11: 264-275, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20197778/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20197778</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20197778" 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/nrm2861" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Wells1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wells, D., Hoffman, D., Kedes, L.
|
|
<strong>Unusual structure, evolutionary conservation of non-coding sequences and numerous pseudogenes characterize the H3.3 histone multigene family.</strong>
|
|
Nucleic Acids Res. 15: 2871-2889, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3031613/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3031613</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3031613" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/nar/15.7.2871" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Wells1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wells, D., Kedes, L.
|
|
<strong>Structure of a human histone cDNA: evidence that basally expressed histone genes have intervening sequences and encode polyadenylated mRNAs.</strong>
|
|
Proc. Nat. Acad. Sci. 82: 2834-2838, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2859593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2859593</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2859593" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.82.9.2834" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Witt1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Witt, O., Albig, W., Doenecke, D.
|
|
<strong>Transcriptional regulation of the human replacement histone gene H3.3B.</strong>
|
|
FEBS Lett. 408: 255-260, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9188772/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9188772</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9188772" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0014-5793(97)00436-5" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Wu2012" class="mim-anchor"></a>
|
|
<div class="">
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Wu, G., Broniscer, A., McEachron, T. A., Lu, C., Paugh, B. S., Becksfort, J., Qu, C., Ding, L., Huether, R., Parker, M., Zhang, J., Gajjar, A., and 9 others.
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<strong>Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas.</strong>
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Nature Genet. 44: 251-253, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22286216/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22286216</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22286216" 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.1102" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="24" class="mim-anchor"></a>
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<a id="Xu2010" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Xu, M., Long, C., Chen, X., Huang, C., Chen, S., Zhu, B.
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<strong>Partitioning of histone H3-H4 tetramers during DNA replication-dependent chromatin assembly.</strong>
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Science 328: 94-98, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20360108/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20360108</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20360108" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.1178994" target="_blank">Full Text</a>]
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</p>
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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 : 05/18/2022
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<div class="row collapse" id="mimCollapseContributors">
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<span class="mim-text-font">
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Anne M. Stumpf - updated : 02/01/2022<br>Cassandra L. Kniffin - updated : 01/28/2022<br>Ada Hamosh - updated : 10/23/2020<br>Paul J. Converse - updated : 04/06/2016<br>Ada Hamosh - updated : 6/24/2015<br>Ada Hamosh - updated : 1/14/2014<br>Ada Hamosh - updated : 6/24/2013<br>Patricia A. Hartz - updated : 2/6/2013<br>Matthew B. Gross - updated : 2/4/2013<br>Ada Hamosh - updated : 12/13/2012<br>Ada Hamosh - updated : 9/6/2012<br>Ada Hamosh - updated : 8/29/2012<br>Ada Hamosh - updated : 3/7/2012<br>Patricia A. Hartz - updated : 5/14/2010<br>Patricia A. Hartz - updated : 5/12/2010<br>Ada Hamosh - updated : 4/28/2010<br>Ada Hamosh - updated : 4/13/2010<br>Ada Hamosh - updated : 3/11/2010<br>Ada Hamosh - updated : 2/1/2010<br>Ada Hamosh - updated : 10/19/2009<br>Ada Hamosh - updated : 9/16/2009<br>Ada Hamosh - updated : 9/9/2009<br>Ada Hamosh - updated : 8/10/2009<br>Cassandra L. Kniffin - updated : 6/8/2009<br>Ada Hamosh - updated : 6/4/2009<br>Ada Hamosh - updated : 5/23/2008<br>Ada Hamosh - updated : 3/26/2008<br>Ada Hamosh - updated : 3/6/2008<br>Ada Hamosh - updated : 2/21/2008<br>Ada Hamosh - updated : 11/26/2007<br>Ada Hamosh - updated : 8/28/2007<br>Ada Hamosh - updated : 8/13/2007<br>Ada Hamosh - updated : 8/15/2006<br>George E. Tiller - updated : 1/31/2006<br>Ada Hamosh - updated : 1/12/2006<br>Ada Hamosh - updated : 11/3/2005<br>Ada Hamosh - updated : 10/25/2005<br>Ada Hamosh - updated : 8/18/2005<br>Ada Hamosh - updated : 12/15/2004<br>Ada Hamosh - updated : 6/17/2003<br>Ada Hamosh - updated : 4/15/2003<br>Ada Hamosh - updated : 11/20/2002<br>Stylianos E. Antonarakis - updated : 1/7/2002<br>Ada Hamosh - updated : 8/14/2001<br>Ada Hamosh - updated : 8/5/1999<br>Rebekah S. Rasooly - updated : 7/8/1998
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</span>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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<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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Alan F. Scott : 3/18/1996
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</span>
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<div class="row">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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mgross : 05/18/2022
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<div class="row collapse" id="mimCollapseEditHistory">
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<span class="mim-text-font">
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alopez : 02/01/2022<br>ckniffin : 01/28/2022<br>mgross : 10/23/2020<br>carol : 11/20/2019<br>mgross : 04/06/2016<br>alopez : 6/24/2015<br>alopez : 6/10/2015<br>alopez : 4/1/2014<br>alopez : 1/14/2014<br>alopez : 6/24/2013<br>mgross : 2/8/2013<br>mgross : 2/6/2013<br>mgross : 2/6/2013<br>mgross : 2/4/2013<br>alopez : 12/21/2012<br>terry : 12/13/2012<br>alopez : 9/7/2012<br>alopez : 9/7/2012<br>terry : 9/6/2012<br>alopez : 9/4/2012<br>terry : 8/29/2012<br>terry : 5/22/2012<br>mgross : 5/3/2012<br>terry : 5/1/2012<br>carol : 4/11/2012<br>alopez : 3/12/2012<br>terry : 3/7/2012<br>terry : 4/20/2011<br>carol : 7/29/2010<br>mgross : 5/17/2010<br>terry : 5/14/2010<br>terry : 5/12/2010<br>alopez : 4/29/2010<br>terry : 4/28/2010<br>alopez : 4/14/2010<br>terry : 4/13/2010<br>carol : 4/5/2010<br>alopez : 3/11/2010<br>alopez : 2/1/2010<br>alopez : 1/27/2010<br>terry : 1/15/2010<br>alopez : 11/9/2009<br>alopez : 10/26/2009<br>terry : 10/19/2009<br>alopez : 9/22/2009<br>alopez : 9/22/2009<br>terry : 9/16/2009<br>terry : 9/9/2009<br>alopez : 8/19/2009<br>mgross : 8/10/2009<br>mgross : 8/10/2009<br>terry : 8/10/2009<br>wwang : 6/17/2009<br>ckniffin : 6/8/2009<br>alopez : 6/4/2009<br>alopez : 6/4/2009<br>joanna : 6/2/2009<br>terry : 5/19/2009<br>alopez : 6/2/2008<br>terry : 5/23/2008<br>alopez : 3/26/2008<br>alopez : 3/26/2008<br>alopez : 3/25/2008<br>terry : 3/6/2008<br>carol : 2/29/2008<br>terry : 2/21/2008<br>alopez : 11/29/2007<br>terry : 11/26/2007<br>alopez : 9/7/2007<br>alopez : 9/7/2007<br>terry : 8/28/2007<br>carol : 8/15/2007<br>terry : 8/13/2007<br>carol : 8/15/2006<br>carol : 8/15/2006<br>carol : 8/15/2006<br>wwang : 1/31/2006<br>alopez : 1/13/2006<br>terry : 1/12/2006<br>alopez : 11/7/2005<br>alopez : 11/7/2005<br>terry : 11/3/2005<br>alopez : 10/26/2005<br>terry : 10/25/2005<br>alopez : 8/23/2005<br>terry : 8/18/2005<br>alopez : 12/15/2004<br>alopez : 6/19/2003<br>terry : 6/17/2003<br>alopez : 4/17/2003<br>terry : 4/15/2003<br>cwells : 11/20/2002<br>terry : 11/18/2002<br>mgross : 1/7/2002<br>alopez : 8/20/2001<br>terry : 8/14/2001<br>alopez : 8/5/1999<br>alopez : 8/5/1999<br>alopez : 8/26/1998<br>alopez : 7/8/1998<br>mark : 9/22/1996<br>terry : 3/26/1996<br>mark : 3/19/1996<br>mark : 3/18/1996
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<h3>
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<span class="mim-font">
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<strong>*</strong> 601128
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<h3>
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<span class="mim-font">
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H3 HISTONE, FAMILY 3A; H3F3A
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</span>
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</h3>
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</div>
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<div>
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<br />
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<h4>
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<span class="mim-font">
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H3F3<br />
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H3.3A
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: H3-3A</em></strong>
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<strong>
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<em>
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Cytogenetic location: 1q42.12
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Genomic coordinates <span class="small">(GRCh38)</span> : 1:226,061,831-226,072,019 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<td rowspan="1">
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<span class="mim-font">
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1q42.12
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</td>
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<td>
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<span class="mim-font">
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Bryant-Li-Bhoj neurodevelopmental syndrome 1
|
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</span>
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</td>
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<td>
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<span class="mim-font">
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619720
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Histones are the basic nuclear proteins responsible for the nucleosome structure within the chromosomal fiber in eukaryotes. Five classes of histone genes have been reported. Some classes are expressed only during S phase, while others are replication independent. The latter are referred to as replacement histones and are expressed in quiescent or terminally differentiated cells. H3.3 is a replacement histone that is encoded by 2 distinct replication-independent genes, H3.3A (H3F3A) and H3.3B (H3F3B; 601058). The proteins encoded by the H3.3A and H3.3B genes are identical (summary by Wells et al. (1987) and Albig et al. (1995)). </p><p>For additional background information on histones, histone gene clusters, and the H3 histone family, see HIST1H3A (602810).</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Cloning and Expression</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Using an H3.3 pseudogene cDNA to probe a human fibroblast cDNA library, Wells and Kedes (1985) cloned H3.3. The transcript contains a long 3-prime poly(A) tail, and the deduced protein contains 135 amino acids. The H3.3 protein has 5 amino acid changes compared with H3.1 (see 602812), but their nucleotide sequences are more divergent. Northern blot analysis detected a transcript of about 1.2 kb in HeLa cell poly(A) RNA. </p><p>Chalmers and Wells (1990) showed that the rabbit H3.3a 3-prime untranslated region is 94% similar to the human sequence of Wells and Kedes (1985), indicating that evolutionary conservation extends beyond the coding region. </p><p>Witt et al. (1997) noted that although the H3.3A and H3.3B proteins are identical, their nucleotide coding sequences and flanking portions differ. They reported that H3.3a was basally expressed in mouse testis, whereas H3.3b was expressed in a stage-specific manner. </p><p>Using Northern blot analysis, Frank et al. (2003) assayed for expression of the replacement histones H3.3A and H3.3B and the cell cycle-dependent histone H3/m (HIST2H3C; 142780) in human tissues and cell lines. All 6 cell lines expressed H3.3A, H3.3B, and H3/m at high levels. Conversely, fetal liver predominantly expressed H3/m, likely due to its rapid cell growth, whereas adult liver, kidney, and heart predominantly expressed H3.3A and H3.3B. The H3.3A transcript was detected at 1.0 kb. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
|
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<p>Wells and Kedes (1985) determined that the 5-prime UTR of the H3F3A gene is GC rich (75%). </p><p>Wells et al. (1987) determined that the H3F3A gene contains 4 exons and spans 8.8 kb. The first exon is noncoding. The 5-prime end contains noncanonical TATA and CCAAT boxes and an SP1 (189906)-binding GC box. The 3-prime end contains 2 potential polyadenylation signals and is highly conserved, sharing 85% identity with the chicken ortholog. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Mapping</strong>
|
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</span>
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</h4>
|
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</div>
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<span class="mim-text-font">
|
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<p>By analysis of a somatic cell hybrid panel and by inclusion within a YAC from that region, Lin and Wells (1997) mapped the H3F3A gene to chromosome 1q41. </p><p>Stumpf (2022) mapped the H3F3A gene to chromosome 1q42.12 based on an alignment of the H3F3A sequence (GenBank BC029405) with the genomic sequence (GRCh38).</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
|
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<p>See HIST1H3A (602810) for functional information on the H3 histone family.</p><p><strong><em>H3.3 Histone</em></strong></p><p>
|
|
Hake et al. (2006) noted that most studies on expression or posttranslational modifications of H3 histones do not differentiate between the H3.1 (see 602810), H3.2 (HIST2H3C; 142780), and H3.3 proteins, in part due to their high degree of amino acid identity. By quantitative PCR of 5 human cell lines, they found that the 9 H3.1 genes, 1 H3.2 gene, and 2 H3.3 genes examined were expressed in a cell line-specific manner. All 3 types of H3 genes were highly expressed during S phase in human cell lines, whereas the H3.3 genes were also highly expressed outside of S phase, consistent with their status as replication-independent genes. Using a combination of isotopic labeling and quantitative tandem mass spectrometry, Hake et al. (2006) showed that the H3.1, H3.2, and H3.3 proteins differed in their posttranslational modifications. H3.1 was enriched in marks associated with both gene activation and gene silencing, H3.2 was enriched in repressive marks associated with gene silencing and the formation of facultative heterochromatin, and H3.3 was enriched in marks associated with transcriptional activation. Hake et al. (2006) concluded that H3.1, H3.2, and H3.3 likely have unique functions and should not be treated as equivalent proteins. </p><p>Jin et al. (2009) characterized the genomewide distribution of nucleosome core particles containing H3.3 and/or H2A.Z (H2AFZ; 142763) in HeLa cells. They found that highly labile particles containing both H3.3 and H2A.Z were enriched at active promoters, enhancers, and insulator regions. Nucleosomes containing H3.3, but not H2A.Z, were also relatively unstable and were detected along the transcribed region of genes and at transcriptional stop sites. Jin et al. (2009) suggested that unstable particles containing both H3.3 and H2A.Z may serve as place holders that are easily displaced by transcription factors. They proposed that unstable particles containing only H3.3 along the transcribed portions of genes may accommodate the passage of RNA polymerase. </p><p>Xu et al. (2010) reported that significant amounts of histone H3.3-H4 (see 602822) tetramers split in vivo, whereas most H3.1 (see 602810)-H4 tetramers remain intact during mitotic division. Inhibiting DNA replication-dependent deposition greatly reduced the level of splitting events, which suggested that (i) the replication-independent H3.3 deposition pathway proceeds largely by cooperatively incorporating 2 new H3.3-H4 dimers, and (ii) the majority of splitting events occur during replication-dependent deposition. Xu et al. (2010) concluded that 'silent' histone modifications within large heterochromatic regions are maintained by copying modifications from neighboring preexisting histones without the need for H3-H4 splitting events. </p><p>Talbert and Henikoff (2010) reviewed the assembly of canonical nucleosomes, which is thought to begin with a tetramer of 2 H3 molecules and 2 H4 molecules held together by strong bonds between the H3 molecules. H3.1 is the major canonical H3 assembled into chromatin by the histone chaperone CAF1 (see 601246) complex during DNA replication and repair. The replacement histone H3.3 is assembled by the histone regulator A (HIRA; 600237) complex independently of DNA synthesis. </p><p>Using knockdown analysis, Banaszynski et al. (2013) showed that depletion of H3.3 (i.e., both H3f3A and H3f3b) in mouse embryonic stem cells (ESCs) resulted in globally reduced chromatin dynamics at promoters and reduced H3K27me3 enrichment at promoters of developmentally regulated bivalent genes. Reduction of H3K27me3 enrichment at bivalent genes upregulated expression of transcription factors essential for trophectoderm specification in ESCs, likely due to perturbation of the balance between activation-associated H3K4me3 and repression-associated H3K27me3 on the promoters. H3.3-depleted ESCs could differentiate toward the typically restricted trophectoderm lineage, as H3.3-dependent reduction of H3K27me3 enrichment at developmentally regulated promoters resulted in gene misregulation upon differentiation rather than deregulation in the pluripotent state. H3.3 facilitated the proper chromatin environment for occupancy of the Polycomb repressive complex-2 (PRC2; see 301036) at its target regions and/or for PRC2 activity toward H3, regardless of H3 isoform. Consequently, H3.3 depletion-induced reduction of H3K27me3 levels reduced PRC2 enrichment and activity at promoters of bivalent genes in ESCs. Deposition of H3.3 at promoters of developmentally regulated genes to establish a bivalent chromatin landscape in ESCs was dependent on Hira. Hira colocalized with promoter-proximal RNA polymerase II (see 180660) and PRC2 at promoters of developmentally regulated genes in ESCs, and Hira -/- ESCs recapitulated the loss of H3K27me3 and PRC2 at bivalent promoters observed in H3.3-depleted ESCs. Recruitment of PRC2 to promoters was H3.3 dependent, as Hira interacted with PRC2, and the interaction required H3.3. </p><p>Elsasser et al. (2015) showed that the replacement histone variant H3.3 is enriched at class I and class II endogenous retroviral elements (ERVs), notably those of the early transposon/MusD family and intracisternal A-type particles. Deposition at a subset of these elements is dependent on the H3.3 chaperone complex containing ATRX (300032) and DAXX (603186). Elsasser et al. (2015) demonstrated that recruitment of DAXX, H3.3, and KAP1 (TRIM28; 601742) to ERVs is codependent and occurs upstream of ESET (SETDB1; 604396), linking H3.3 to ERV-associated H3K9me3. Importantly, H3K9me3 is reduced at ERVs upon H3.3 deletion, resulting in derepression and dysregulation of adjacent, endogenous genes, along with increased retrotransposition of intracisternal A-type particles. Elsasser et al. (2015) concluded that their study identifies a unique heterochromatin state marked by the presence of both H3.3 and H3K9me3, and establishes an important role for H3.3 in control of ERV retrotransposition in embryonic stem cells. </p><p>The N terminus of H3.3 contains a unique serine, ser31, that is absent in canonical H3.1 and H3.2. Armache et al. (2020) showed that ser31 was phosphorylated in a stimulation-dependent manner along rapidly induced genes in mouse macrophages. This selective mark of stimulation-responsive genes directly engaged Setd2 (612778), a component of the active transcription machinery, and ejected the elongation corepressor Zmynd11 (608668). Armache et al. (2020) proposed that features of H3.3 at stimulation-induced genes, including phosphorylated ser31, provide preferential access to the transcription apparatus. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Biochemical Features</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p><strong><em>Crystal Structure</em></strong></p><p>
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Elsasser et al. (2012) reported the crystal structures of the DAXX (603186) histone-binding domain with a histone H3.3-H4 (see 602822) dimer, including mutants within DAXX and H3.3, together with in vitro and in vivo functional studies that elucidated the principles underlying H3.3 recognition specificity. Occupying 40% of the histone surface-accessible area, DAXX wraps around the H3.3-H4 dimer, with complex formation accompanied by structural transitions in the H3.3-H4 histone fold. DAXX uses an extended alpha-helical conformation to compete with major interhistone, DNA, and ASF1 interaction sites. Elsasser et al. (2012) concluded that their structural studies identified recognition elements that read out H3.3-specific residues, and functional studies addressed the contribution of gly90 in H3.3 and glu225 in DAXX to chaperone-mediated H3.3 variant recognition specificity. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p><strong><em>Somatic Mutations</em></strong></p><p>
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Schwartzentruber et al. (2012) sequenced the exomes of 48 pediatric glioblastoma (137800) samples. Somatic mutations in the H3.3-ATRX (300032)-DAXX (603186) chromatin remodeling pathway were identified in 44% of tumors (21 of 48). Recurrent mutations in H3F3A, which encodes the replication-independent histone-3 variant H3.3, were observed in 31% of tumors, and led to amino acid substitutions at 2 critical positions within the histone tail (K27M, G34R/G34V) involved in key regulatory posttranslational modifications. Mutations in ATRX and DAXX, encoding 2 subunits of a chromatin remodeling complex required for H3.3 incorporation at pericentric heterochromatin and telomeres, were identified in 31% of samples overall, and in 100% of tumors harboring a G34R or G34V H3.3 mutation. Somatic TP53 (191170) mutations were identified in 54% of all cases, and in 86% of samples with H3F3A and/or ATRX mutations. Screening of a large cohort of gliomas of various grades and histologies (n = 784) showed H3F3A mutations to be specific to glioblastoma multiforme and highly prevalent in children and young adults. Furthermore, the presence of H3F3A/ATRX-DAXX/TP53 mutations was strongly associated with alternative lengthening of telomeres and specific gene expression profiles. Schwartzentruber et al. (2012) stated that this was the first report to highlight recurrent mutations in a regulatory histone in humans, and that their data suggested that defects of the chromatin architecture underlie pediatric and young adult glioblastoma multiforme pathogenesis. </p><p>Wu et al. (2012) reported that a K27M mutation occurring in either H3F3A or HIST1H3B (602819) was observed in 78% of diffuse intrinsic pontine gliomas (DIPGs) and 22% of non-brain-stem gliomas. </p><p>Lewis et al. (2013) reported that human DIPGs containing the K27M mutation in either histone H3.3 (H3F3A) or H3.1 (HIST1H3B) display significantly lower overall amounts of H3 with trimethylated lysine-27 (H3K27me3) and that histone H3K27M transgenes are sufficient to reduce the amounts of H3K27me3 in vitro and in vivo. Lewis et al. (2013) found that H3K27M inhibits the enzymatic activity of the Polycomb repressive complex-2 (PRC2) through interaction with the EZH2 (601573) subunit. In addition, transgenes containing lysine-to-methionine substitutions at other known methylated lysines (H3K9 and H3K36) are sufficient to cause specific reduction in methylation through inhibition of SET domain enzymes. Lewis et al. (2013) proposed that K-to-M substitutions may represent a mechanism to alter epigenetic states in a variety of pathologies. </p><p>Behjati et al. (2013) reported exquisite tumor type specificity for different histone H3.3 driver alterations. In 73 of 77 cases (95%) of chondroblastoma, Behjati et al. (2013) found K36M alterations predominantly encoded by H3F3B (601058), which is 1 of 2 genes for histone H3.3. In contrast, in 92% (49 of 53) of giant cell tumors of bone, Behjati et al. (2013) found histone H3.3 alterations exclusively in H3F3A, leading to G34W or, in 1 case, G34L alterations. The mutations were restricted to the stromal cell population and were not detected in osteoclasts or their precursors. In the context of previously reported H3F3A mutations encoding K27M and G34R or G34V alterations in childhood brain tumors, a picture of tumor type specificity for histone H3.3 driver alterations emerged, indicating that histone H3.3 residues, mutations, and genes have distinct functions. </p><p>Diffuse intrinsic pediatric gliomas (DIPGs) are rare, highly aggressive brainstem tumors. Over 70% of DIPGs harbor somatic mutations in the H3F3A gene that result in a lys27-to-met (K27M) substitution. Tumors that are positive for the mutation are associated with a poor prognosis and diminished survival. Funato et al. (2014) used a human embryonic stem cell system to model this tumor, and showed that H3.3K27M expression synergizes with loss of p53 (191170) and activation of PDGFRA (173490) in neural progenitor cells derived from human embryonic stem cells, resulting in neoplastic transformation. Genomewide analyses indicated a resetting of the transformed precursors to a developmentally more primitive stem cell state, with evidence of major modifications of histone marks at several master regulator genes. Drug screening assays identified a compound targeting the protein menin (613733) as an inhibitor of tumor cell growth in vitro and in mice. </p><p><strong><em>Bryant-Li-Bhoj Neurodevelopmental Syndrome 1</em></strong></p><p>
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In 33 unrelated patients with Bryant-Li-Bhoj neurodevelopmental syndrome-1 (BRYLIB1; 619720), Bryant et al. (2020) identified de novo heterozygous missense mutations in the H3F3A gene (see, e.g., 601128.0001-601128.0005). The mutations, which were found by whole-exome or genome sequencing, occurred throughout the gene. All but 1 were absent from the gnomAD database. In vitro studies of lymphoblasts or fibroblasts derived from a subset of patients showed that the distribution of posttranslational modification (PTM) histone abundances was similar to controls. The overall histone PTM variation was slightly increased in controls compared to patients. Nonetheless, some histone PTMs were altered in patients compared to controls. The findings suggested that mutant histones can be incorporated into the nucleosome and cause local deregulation of the chromatin state with modest alterations in the control of histone modification. This could affect multiple histone functions, including gene expression, chromatin stability, DNA damage repair, and differentiation. RNA sequencing of a subset of pooled patient cells showed upregulation of genes involved in mitosis, and in vitro studies of pooled patient fibroblast lines showed increased cellular proliferation compared to controls; viability of patient cells was similar to controls. In silico molecular modeling of the mutations suggested 3 broad scenarios for the variants' impact: disruption of H3.3 DNA binding; disrupted formation of the histone octamer or binding with other histones; and disruption of histone-protein binding to chaperones or other interacting proteins. There were no genotype/phenotype correlations. None of the patients developed cancer. </p><p>In 6 unrelated patients with BRYLIB1, Okur et al. (2021) identified 6 different de novo heterozygous missense mutations at highly conserved residues in the H3F3A gene (see, e.g., 601128.0003; 601128.0004; 601128.0006-601128.0007). The mutations, which were found by exome sequencing, were absent from the gnomAD database. Expression of a subset of variants in HEK293 cells showed that some resulted in decreased protein levels, whereas 1 (R41C; 601128.0006) increased protein levels compared to controls. Additional functional studies of some of the variants showed that 1 (R129H; 601128.0007) had a significantly stronger interaction with DAXX (603186) compared to controls, which might lead to aberrant transcription. The mutant proteins localized normally to the nucleus. Molecular modeling suggested that some, but not all, mutations might alter the PTMs of histone H3.3. The possible molecular pathomechanism of other mutations was unclear. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Jang et al. (2015) reported that deletion of H3f3a or H3f3b in mice had no apparent deleterious impact on phenotype or fertility. However, knockout of both genes (H3.3 DKO) led to developmental retardation and embryonic lethality. H3.3 DKO embryos showed reduced cell proliferation and increased cell death. Embryonic stem cells from H3.3 DKO mice had mitotic defects. Growth retardation could be rescued by deletion of p53. RNA sequencing analysis revealed that p53 -/- H3.3 DKO embryos had only limited changes to the transcriptome. H3.3 DKO mouse embryonic fibroblasts lacking p53 proliferated but showed mitotic abnormalities associated with defects in chromosomal heterochromatic structures at telomeres, centromeres, and pericentromeric regions, as well as genome instability. Karyotypic abnormalities and DNA damage in H3.3 DKO mice led to p53 pathway activation. Jang et al. (2015) concluded that H3.3 supports chromosomal heterochromatic structures, thus maintaining genome integrity during mammalian development. </p><p>Bryant et al. (2020) noted that zebrafish with a dominant D123N mutation in the h3f3a gene developed craniofacial abnormalities. Homozygous knockdown of the h3f3a gene resulted in a loss of neural crest-derived jaw cartilages. There was also a partial reduction in Foxd3 (611539)-derived cranial glia, melanocytes, and xanthophores; those injected with dominant-negative h3f3a showed a further reduction in these cell types. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>7 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 BRYANT-LI-BHOJ NEURODEVELOPMENTAL SYNDROME 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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H3F3A, ARG18GLY
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<br />
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SNP: rs2102735576,
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ClinVar: RCV001823808, RCV003107859
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 unrelated children (patients 4 and 5) with Bryant-Li-Bhoj neurodevelopmental syndrome-1 (BRYLIB1; 619720), Bryant et al. (2020) identified a de novo heterozygous c.52A-G transition (c.52A-G, NM_002107.4) in the H3F3A gene, resulting in an arg18-to-gly (R18G) substitution. The mutation, which was found by exome sequencing, was not present in the gnomAD database. The authors noted that this mutation would be described as ARG17GLY (R17G) according to standard histone nomenclature, which omits numbering the initiator methionine. In vitro studies of pooled patient cells showed some evidence of dysregulated histone posttranslational modifications as well as enhanced proliferation. Both patients had global developmental delay with late walking, absent speech, hypotonia, and dysmorphic facial features. One had controlled seizures and the other was tube-fed for a short time. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 BRYANT-LI-BHOJ NEURODEVELOPMENTAL SYNDROME 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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H3F3A, THR46ILE
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<br />
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SNP: rs1657901999,
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ClinVar: RCV001266185, RCV001823766
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 4 unrelated patients (patients 11-14) with Bryant-Li-Bhoj neurodevelopmental syndrome-1 (BRYLIB1; 619720), Bryant et al. (2020) identified a de novo heterozygous c.137C-T transition (c.137C-T, NM_002107.4) in the H3F3A gene, resulting in a thr46-to-ile (T46I) substitution. The mutation, which was found by exome sequencing, was not present in the gnomAD database. The authors noted that this mutation would be described as THR45ILE (T45I) according to standard histone nomenclature, which omits numbering the initiator methionine. Analysis of pooled patient cells showed some evidence of dysregulated histone posttranslational modifications. In vitro studies of pooled patient cells showed some evidence of dysregulated histone posttranslational modifications as well as enhanced proliferation. The patients had global developmental delay with late walking, poor or absent speech, hypotonia, and dysmorphic features. One patient had seizures. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 BRYANT-LI-BHOJ NEURODEVELOPMENTAL SYNDROME 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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H3F3A, GLY91ARG
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<br />
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SNP: rs2102737050,
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ClinVar: RCV001541911, RCV001823779
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In an 8-year-old girl (patient 20) with Bryant-Li-Bhoj neurodevelopmental syndrome-1 (BRYLIB1; 619720), Bryant et al. (2020) identified a de novo heterozygous c.271G-C transversion (c.271G-C, NM_002107.4) in the H3F3A gene, resulting in a gly91-to-arg (G91R) substitution. The mutation, which was found by exome sequencing, was not present in the gnomAD database. The authors noted that this mutation would be described as GLY90ARG (G90R) according to standard histone nomenclature, which omits numbering the initiator methionine. Molecular modeling suggested that the mutation could disrupt chaperone binding. In vitro studies of pooled patient cells showed some evidence of dysregulated histone posttranslational modifications as well as enhanced proliferation. The patient had severe global developmental delay with inability to walk or speak. She also had progressive short stature, hypo/hypertonia, and dysmorphic facial features. </p><p>In a 28-year-old female (patient 2) with BRYLIB1, Okur et al. (2021) identified a de novo heterozygous G91R mutation in the H3F3A gene. The mutant protein localized normally to the nucleus and was expressed at normal levels. Molecular modeling suggested that the mutation would not have an effect on histone PTM. The patient had short stature, global developmental delay, microcephaly, hypotonia, hypertonia of the extremities, and seizures. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 BRYANT-LI-BHOJ NEURODEVELOPMENTAL SYNDROME 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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H3F3A, PRO122LEU
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<br />
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SNP: rs1576203003,
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ClinVar: RCV000851307, RCV001541913, RCV001823747, RCV004017756
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In an 18-month-old girl (patient 27) with Bryant-Li-Bhoj neurodevelopmental syndrome-1 (BRYLIB1; 619720), Bryant et al. (2020) identified a de novo heterozygous c.365C-T transition (c.365C-T, NM_002107.4) in the H3F3A gene, resulting in a pro122-to-leu (P122L) substitution. The mutation, which was found by exome sequencing, was not present in the gnomAD database. The authors noted that this mutation would be described as PRO121LEU (P121L) according to standard histone nomenclature, which omits numbering the initiator methionine. Functional studies of the variant and studies of patient cells were not performed. The patient had global developmental delay with inability to walk or speak, hypotonia, focal epilepsy, dysmorphic facial features, and delayed visual tracking. </p><p>In a 13-year-old boy (patient 3) with BRYLIB1, Okur et al. (2021) identified a de novo heterozygous P122L mutation in the H3F3A gene. The mutant protein localized normally to the nucleus and was expressed at normal levels. Additional functional studies of the variant were not performed, but molecular modeling suggested that the mutation would not affect histone PTM. The patient had short stature, global developmental delay, microcephaly, hypotonia, and seizures. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0005 BRYANT-LI-BHOJ NEURODEVELOPMENTAL SYNDROME 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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H3F3A, GLN126ARG
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<br />
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SNP: rs1276519904,
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ClinVar: RCV000624606, RCV000994267, RCV001823740, RCV004555590
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 4 unrelated patients (patients 29-32) with Bryant-Li-Bhoj neurodevelopmental syndrome-1 (BRYLIB1; 619720), Bryant et al. (2020) identified a de novo heterozygous c.377A-G transition (c.377A-G, NM_002107.4) in the last exon of the H3F3A gene, resulting in a gln126-to-arg (Q126R) substitution. The mutation, which was found by genome sequencing, was not present in the gnomAD database. The authors noted that this mutation would be described as GLN125ARG (Q125R) according to standard histone nomenclature, which omits numbering the initiator methionine. In vitro functional studies of the variant and studies of patient cells were not performed, but molecular modeling predicted that it could disrupt assembly of the histone octomer by affecting intramonomer contacts. The patients had severe global developmental delay, hypotonia, seizures, dysmorphic features, and brain imaging abnormalities. One was tube-fed, and another died at 10 months of age. None achieved walking or language, including the oldest who was 15 years of age. Two patients showed neurologic regression. </p>
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</span>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0006 BRYANT-LI-BHOJ NEURODEVELOPMENTAL SYNDROME 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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H3F3A, ARG41CYS
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<br />
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SNP: rs2102735801,
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ClinVar: RCV001541909, RCV001823778
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</span>
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</div>
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<span class="mim-text-font">
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<p>In a patient with Bryant-Li-Bhoj neurodevelopmental syndrome-1 (BRYLIB1; 619720), Okur et al. (2021) identified a de novo heterozygous c.121C-T transition (c.121C-T, NM_002107.7) in the H3F3A gene, resulting in an arg41-to-cys (R41C) substitution at a conserved residue. The mutation was found by exome sequencing; it was not present in the gnomAD database. Expression of the mutation in HEK293 cells showed that it caused increased protein levels compared to controls. The mutant protein localized normally to the nucleus. </p>
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</span>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0007 BRYANT-LI-BHOJ NEURODEVELOPMENTAL SYNDROME 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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H3F3A, ARG129HIS
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<br />
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SNP: rs1658121882,
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ClinVar: RCV001541914, RCV001823780
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a 4.5-year-old boy (patient 4) with Bryant-Li-Bhoj neurodevelopmental syndrome-1 (BRYLIB1; 619720), Okur et al. (2021) identified a de novo heterozygous c.386G-A transition (c.386G-A, NM_002107.7) in the H3F3A gene, resulting in an arg129-to-his (R129H) substitution at a conserved residue. The mutation was found by exome sequencing; it was not present in the gnomAD database. In vitro functional studies showed that the R129H mutant protein had a significantly stronger interaction with DAXX (603186) compared to controls, which might lead to aberrant transcription. The mutant protein localized normally to the nucleus. Molecular modeling suggested that the mutation would not alter the PTM of histone H3.3. The patient had short stature, global developmental delay, hypotonia, and dysmorphic features. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
|
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</div>
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<div>
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<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Albig, W., Bramlage, B., Gruber, K., Klobeck, H.-G., Kunz, J., Doenecke, D.
|
|
<strong>The human replacement histone H3.3B gene (H3F3B).</strong>
|
|
Genomics 30: 264-272, 1995.
|
|
|
|
|
|
[PubMed: 8586426]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1995.9878]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Armache, A., Yang, S., Martinez de Paz, A., Robbins, L. E., Durmaz, C., Cheong, J. Q., Ravishankar, A., Daman, A. W., Ahimovic, D. J., Klevorn, T., Yue, Y., Arslan, T., and 13 others.
|
|
<strong>Histone H3.3 phosphorylation amplifies stimulation-induced transcription.</strong>
|
|
Nature 583: 852-857, 2020.
|
|
|
|
|
|
[PubMed: 32699416]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/s41586-020-2533-0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Banaszynski, L. A., Wen, D., Dewell, S., Whitcomb, S. J., Lin, M., Diaz, N., Elsasser, S. J., Chapgier, A., Goldberg, A. D., Canaani, E., Rafii, S., Zheng, D., Allis, C. D.
|
|
<strong>Hira-dependent histone H3.3 deposition facilitates PRC2 recruitment at developmental loci in ES cells.</strong>
|
|
Cell 155: 107-120, 2013.
|
|
|
|
|
|
[PubMed: 24074864]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.cell.2013.08.061]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Behjati, S., Tarpey, P. S., Presneau, N., Scheipl, S., Pillay, N., Van Loo, P., Wedge, D. C., Cooke, S. L., Gundem, G., Davies, H., Nik-Zainal, S., Martin, S., and 17 others.
|
|
<strong>Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone.</strong>
|
|
Nature Genet. 45: 1479-1482, 2013. Note: Erratum: Nature Genet. 46: 316 only, 2014.
|
|
|
|
|
|
[PubMed: 24162739]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng.2814]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bryant, L., Li, D., Cox, S. G., Marchione, D., Joiner, E. F., Wilson, K., Janssen, K., Lee, P., March, M. E., Nair, D., Sherr, E., Fregeau, B., and 119 others.
|
|
<strong>Histone H3.3 beyond cancer: germline mutations in histone 3 family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients.</strong>
|
|
Sci. Adv. 6: eabc9207, 2020.
|
|
|
|
|
|
[PubMed: 33268356]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/sciadv.abc9207]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chalmers, M., Wells, D.
|
|
<strong>Extreme sequence conservation characterizes the rabbit H3.3A histone cDNA.</strong>
|
|
Nucleic Acids Res. 18: 3075, 1990.
|
|
|
|
|
|
[PubMed: 2349118]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/nar/18.10.3075]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Elsasser, S. J., Huang, H., Lewis, P. W., Chin, J. W., Allis, C. D., Patel, D. J.
|
|
<strong>DAXX envelops a histone H3.3-H4 dimer for H3.3-specific recognition.</strong>
|
|
Nature 491: 560-565, 2012.
|
|
|
|
|
|
[PubMed: 23075851]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature11608]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Elsasser, S. J., Noh, K.-M., Diaz, N., Allis, C. D., Banaszynski, L. A.
|
|
<strong>Histone H3.3 is required for endogenous retroviral element silencing in embryonic stem cells.</strong>
|
|
Nature 522: 240-244, 2015.
|
|
|
|
|
|
[PubMed: 25938714]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature14345]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Frank, D., Doenecke, D., Albig, W.
|
|
<strong>Differential expression of human replacement and cell cycle dependent H3 histone genes.</strong>
|
|
Gene 312: 135-143, 2003.
|
|
|
|
|
|
[PubMed: 12909349]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0378-1119(03)00609-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Funato, K., Major, T., Lewis, P. W., Allis, C. D., Tabar, V.
|
|
<strong>Use of human embryonic stem cells to model pediatric gliomas with H3.3K27M histone mutation.</strong>
|
|
Science 346: 1529-1533, 2014.
|
|
|
|
|
|
[PubMed: 25525250]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1253799]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hake, S. B., Garcia, B. A., Duncan, E. M., Kauer, M., Dellaire, G., Shabanowitz, J., Bazett-Jones, D. P., Allis, C. D., Hunt, D. F.
|
|
<strong>Expression patterns and post-translational modifications associated with mammalian histone H3 variants.</strong>
|
|
J. Biol. Chem. 281: 559-568, 2006.
|
|
|
|
|
|
[PubMed: 16267050]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M509266200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jang, C.-W., Shibata, Y., Starmer, J., Yee, D., Magnuson, T.
|
|
<strong>Histone H3.3 maintains genome integrity during mammalian development.</strong>
|
|
Genes Dev. 29: 1377-1392, 2015.
|
|
|
|
|
|
[PubMed: 26159997]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1101/gad.264150.115]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jin, C., Zang, C., Wei, G., Cui, K., Peng, W., Zhao, K., Felsenfeld, G.
|
|
<strong>H3.3/H2A.Z double variant-containing nucleosomes mark 'nucleosome-free regions' of active promoters and other regulatory regions.</strong>
|
|
Nature Genet. 41: 941-945, 2009.
|
|
|
|
|
|
[PubMed: 19633671]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng.409]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lewis, P. W., Muller, M. M., Koletsky, M. S., Cordero, F., Lin, S., Banaszynski, L. A., Garcia, B. A., Muir, T. W., Becher, O. J., Allis, C. D.
|
|
<strong>Inhibition of PRC2 activity by a gain-of-function H3 mutation found in pediatric glioblastoma.</strong>
|
|
Science 340: 857-861, 2013.
|
|
|
|
|
|
[PubMed: 23539183]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1232245]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lin, X., Wells, D. E.
|
|
<strong>Localization of the human H3F3A histone gene to 1q41, outside of the normal histone gene clusters.</strong>
|
|
Genomics 46: 526-528, 1997.
|
|
|
|
|
|
[PubMed: 9441765]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1997.5037]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Okur, V., Chen, Z., Vossaert, L., Peacock, S., Rosenfeld, J., Zhao, L., Du, H., Calamaro, E., Gerard, A., Zhao, S., Kelsay, J., Lahr, A., and 26 others.
|
|
<strong>De novo variants in H3-3A and H3-3B are associated with neurodevelopmental delay, dysmorphic features, and structural brain abnormalities.</strong>
|
|
NPJ Genom. Med. 6: 104, 2021.
|
|
|
|
|
|
[PubMed: 34876591]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/s41525-021-00268-8]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schwartzentruber, J., Korshunov, A, Liu, X.-Y., Jones, D. T. W., Pfaff, E., Jacob, K., Sturm, D., Fontebasso, A. M., Quang, D.-A. K., Tonjes, M., Hovestadt, V., Albrecht, S., and 50 others.
|
|
<strong>Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma.</strong>
|
|
Nature 482: 226-231, 2012. Note: Erratum: Nature 484: 130 only, 2012.
|
|
|
|
|
|
[PubMed: 22286061]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature10833]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Stumpf, A. M.
|
|
<strong>Personal Communication.</strong>
|
|
Baltimore, Md. 02/01/2022.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Talbert, P. B., Henikoff, S.
|
|
<strong>Histone variants--ancient wrap artists of the epigenome.</strong>
|
|
Nature Rev. Molec. Cell Biol. 11: 264-275, 2010.
|
|
|
|
|
|
[PubMed: 20197778]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nrm2861]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wells, D., Hoffman, D., Kedes, L.
|
|
<strong>Unusual structure, evolutionary conservation of non-coding sequences and numerous pseudogenes characterize the H3.3 histone multigene family.</strong>
|
|
Nucleic Acids Res. 15: 2871-2889, 1987.
|
|
|
|
|
|
[PubMed: 3031613]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/nar/15.7.2871]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wells, D., Kedes, L.
|
|
<strong>Structure of a human histone cDNA: evidence that basally expressed histone genes have intervening sequences and encode polyadenylated mRNAs.</strong>
|
|
Proc. Nat. Acad. Sci. 82: 2834-2838, 1985.
|
|
|
|
|
|
[PubMed: 2859593]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.82.9.2834]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Witt, O., Albig, W., Doenecke, D.
|
|
<strong>Transcriptional regulation of the human replacement histone gene H3.3B.</strong>
|
|
FEBS Lett. 408: 255-260, 1997.
|
|
|
|
|
|
[PubMed: 9188772]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0014-5793(97)00436-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wu, G., Broniscer, A., McEachron, T. A., Lu, C., Paugh, B. S., Becksfort, J., Qu, C., Ding, L., Huether, R., Parker, M., Zhang, J., Gajjar, A., and 9 others.
|
|
<strong>Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas.</strong>
|
|
Nature Genet. 44: 251-253, 2012.
|
|
|
|
|
|
[PubMed: 22286216]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng.1102]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
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Xu, M., Long, C., Chen, X., Huang, C., Chen, S., Zhu, B.
|
|
<strong>Partitioning of histone H3-H4 tetramers during DNA replication-dependent chromatin assembly.</strong>
|
|
Science 328: 94-98, 2010.
|
|
|
|
|
|
[PubMed: 20360108]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1178994]
|
|
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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>
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</div>
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</div>
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<div>
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<div class="row">
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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<span class="text-nowrap mim-text-font">
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Contributors:
|
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Bao Lige - updated : 05/18/2022<br>Anne M. Stumpf - updated : 02/01/2022<br>Cassandra L. Kniffin - updated : 01/28/2022<br>Ada Hamosh - updated : 10/23/2020<br>Paul J. Converse - updated : 04/06/2016<br>Ada Hamosh - updated : 6/24/2015<br>Ada Hamosh - updated : 1/14/2014<br>Ada Hamosh - updated : 6/24/2013<br>Patricia A. Hartz - updated : 2/6/2013<br>Matthew B. Gross - updated : 2/4/2013<br>Ada Hamosh - updated : 12/13/2012<br>Ada Hamosh - updated : 9/6/2012<br>Ada Hamosh - updated : 8/29/2012<br>Ada Hamosh - updated : 3/7/2012<br>Patricia A. Hartz - updated : 5/14/2010<br>Patricia A. Hartz - updated : 5/12/2010<br>Ada Hamosh - updated : 4/28/2010<br>Ada Hamosh - updated : 4/13/2010<br>Ada Hamosh - updated : 3/11/2010<br>Ada Hamosh - updated : 2/1/2010<br>Ada Hamosh - updated : 10/19/2009<br>Ada Hamosh - updated : 9/16/2009<br>Ada Hamosh - updated : 9/9/2009<br>Ada Hamosh - updated : 8/10/2009<br>Cassandra L. Kniffin - updated : 6/8/2009<br>Ada Hamosh - updated : 6/4/2009<br>Ada Hamosh - updated : 5/23/2008<br>Ada Hamosh - updated : 3/26/2008<br>Ada Hamosh - updated : 3/6/2008<br>Ada Hamosh - updated : 2/21/2008<br>Ada Hamosh - updated : 11/26/2007<br>Ada Hamosh - updated : 8/28/2007<br>Ada Hamosh - updated : 8/13/2007<br>Ada Hamosh - updated : 8/15/2006<br>George E. Tiller - updated : 1/31/2006<br>Ada Hamosh - updated : 1/12/2006<br>Ada Hamosh - updated : 11/3/2005<br>Ada Hamosh - updated : 10/25/2005<br>Ada Hamosh - updated : 8/18/2005<br>Ada Hamosh - updated : 12/15/2004<br>Ada Hamosh - updated : 6/17/2003<br>Ada Hamosh - updated : 4/15/2003<br>Ada Hamosh - updated : 11/20/2002<br>Stylianos E. Antonarakis - updated : 1/7/2002<br>Ada Hamosh - updated : 8/14/2001<br>Ada Hamosh - updated : 8/5/1999<br>Rebekah S. Rasooly - updated : 7/8/1998
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Alan F. Scott : 3/18/1996
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