3512 lines
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Entry
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- *600124 - HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN A2/B1; HNRNPA2B1
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- OMIM
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<p>
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<span class="h4">*600124</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/600124">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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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000122566;t=ENST00000618183" 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=3181" 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=600124" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000122566;t=ENST00000618183" 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_002137,NM_031243,XM_005249729,XM_017012109,XM_017012110,XM_047420298,XM_047420299,XM_047420300,XM_047420301,XM_047420302,XM_047420303,XM_047420304,XM_047420305,XM_047420306,XR_001744665,XR_001744666,XR_001744670,XR_001744671,XR_001744672,XR_001744673,XR_001744674,XR_002956424,XR_007060011,XR_007060012,XR_007060013,XR_007060014,XR_007060015,XR_007060016,XR_007060017,XR_242076,XR_242077,XR_428077" 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_002137" 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=600124" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=02526&isoform_id=02526_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/HNRNPA2B1" 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/133257,337449,337453,500638,565643,565644,4504447,14043072,31455238,119614240,119614241,119614242,119614243,119614244,119614245,119614246,119614247,158259881,308219190,530384720,1034655292,1034655298,2217366844,2217366848,2217366858,2217366864,2217366867,2217366871,2217366873,2217366877,2217366880,2462614015,2462614019,2462614024,2462614028,2462614031,2462614036,2462614038,2462614041,2462614045,2462614047,2462614051,2462614054" 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/P22626" 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=3181" 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=ENSG00000122566;t=ENST00000618183" 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=HNRNPA2B1" 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=HNRNPA2B1" 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+3181" 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/HNRNPA2B1" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></dd>
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<dd><a href="https://monarchinitiative.org/NCBIGene:3181" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/3181" 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=chr7&hgg_gene=ENST00000618183.5&hgg_start=26189927&hgg_end=26200746&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:5033" 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=600124[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=600124[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000122566" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.gwascentral.org/search?q=HNRNPA2B1" 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=HNRNPA2B1" 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=HNRNPA2B1&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/PA162391140" 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:5033" 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/FBgn0001215.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:104819" 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/HNRNPA2B1#HomologGenesPanel" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></div>
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<div><a href="http://www.informatics.jax.org/marker/MGI:104819" 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/3181/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=3181" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00001999;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
|
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<span class="small">
|
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:3181" 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=HNRNPA2B1&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>
|
|
600124
|
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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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HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN A2/B1; HNRNPA2B1
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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">
|
|
HNRPA2B1
|
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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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<a id="includedTitles" class="mim-anchor"></a>
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<div>
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<p>
|
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<span class="mim-font">
|
|
Other entities represented in this entry:
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<span class="h3 mim-font">
|
|
HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN A2, INCLUDED; HNRPA2, INCLUDED
|
|
</span>
|
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</div>
|
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|
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<div>
|
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<span class="h4 mim-font">
|
|
|
|
HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN B1, INCLUDED; HNRPB1, INCLUDED
|
|
</span>
|
|
</div>
|
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</div>
|
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<div>
|
|
<br />
|
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</div>
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</div>
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<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=HNRNPA2B1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">HNRNPA2B1</a></em></strong>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/7/127?start=-3&limit=10&highlight=127">7p15.2</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr7:26189927-26200746&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'})">7:26,189,927-26,200,746</a> </span>
|
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</em>
|
|
</strong>
|
|
<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>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=615422,620460" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/7/127?start=-3&limit=10&highlight=127">
|
|
7p15.2
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
?Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2
|
|
|
|
<span class="mim-tip-hint" title="A question mark (?) indicates that the relationship between the phenotype and gene is provisional">
|
|
<span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span>
|
|
</span>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/615422"> 615422 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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|
|
</span>
|
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</td>
|
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|
|
|
</tr>
|
|
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|
|
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|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Oculopharyngeal muscular dystrophy 2
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/620460"> 620460 </a>
|
|
|
|
</span>
|
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<p>The HNRNPA2B1 gene encodes 2 major proteins, HNRNPA2 and HNRNPB1, through alternative splicing. HNRNPA/B proteins, such as HNRNPA2 and HNRNPB1, are involved in packaging nascent mRNA, in alternative splicing, and in cytoplasmic RNA trafficking, translation, and stabilization. HNRNPA2 and HNRNPB1 also appear to function in telomere maintenance, cell proliferation and differentiation, and glucose transport (<a href="#12" class="mim-tip-reference" title="Moran-Jones, K., Wayman, L., Kennedy, D. D., Reddel, R. R., Sara, S., Snee, M. J., Smith, R. <strong>hnRNP A2, a potential ssDNA/RNA molecular adapter at the telomere.</strong> Nucleic Acids Res. 33: 486-496, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15659580/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15659580</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15659580[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/10.1093/nar/gki203" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15659580">Moran-Jones et al., 2005</a>; <a href="#5" class="mim-tip-reference" title="Iwanaga, K., Sueoka, N., Sato, A., Hayashi, S., Sueoka, E. <strong>Heterogeneous nuclear ribonucleoprotein B1 protein impairs DNA repair mediated through the inhibition of DNA-dependent protein kinase activity.</strong> Biochem. Biophys. Res. Commun. 333: 888-895, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15964549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15964549</a>] [<a href="https://doi.org/10.1016/j.bbrc.2005.05.180" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15964549">Iwanaga et al., 2005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15659580+15964549" 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 immunoscreening a HeLa cell cDNA expression library using mouse anti-A2 and anti-B1 antibodies, followed by screening a human osteosarcoma cDNA library, <a href="#2" class="mim-tip-reference" title="Burd, C. G., Swanson, M. S., Gorlach, M., Dreyfuss, G. <strong>Primary structures of the heterogeneous nuclear ribonucleoprotein A2, B1, and C2 proteins: a diversity of RNA binding proteins is generated by small peptide inserts.</strong> Proc. Nat. Acad. Sci. 86: 9788-9792, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2557628/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2557628</a>] [<a href="https://doi.org/10.1073/pnas.86.24.9788" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2557628">Burd et al. (1989)</a> obtained full-length A2 and B1 clones. The B1 cDNA has a 36-nucleotide insertion near its 5-prime end relative to A2, but they are otherwise identical. The deduced A2 protein contains 341 amino acids, and the deduced B1 protein contains an in-frame 12-amino acid insert after glu2 compared with A2. Both proteins contain 2 consensus-type RNA-binding domains, followed by an extended C-terminal glycine-rich region. The insert in B1 introduces a putative nuclear localization signal. In vitro translation produced A2 and B1 proteins that comigrated with purified endogenous HeLa cell A2 and B1 at apparent molecular masses of 36 and 38 kD, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2557628" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Biamonti, G., Ruggiu, M., Saccone, S., Della Valle, G., Riva, S. <strong>Two homologous genes, originated by duplication, encode the human hnRNP proteins A2 and A1.</strong> Nucleic Acids Res. 22: 1996-2002, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8029005/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8029005</a>] [<a href="https://doi.org/10.1093/nar/22.11.1996" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8029005">Biamonti et al. (1994)</a> and <a href="#9" class="mim-tip-reference" title="Kozu, T., Henrich, B., Schafer, K. P. <strong>Structure and expression of the gene (HNRPA2B1) encoding the human hnRNP protein A2/B1.</strong> Genomics 25: 365-371, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7789969/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7789969</a>] [<a href="https://doi.org/10.1016/0888-7543(95)80035-k" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7789969">Kozu et al. (1995)</a> independently cloned HNRNPA2B1. <a href="#1" class="mim-tip-reference" title="Biamonti, G., Ruggiu, M., Saccone, S., Della Valle, G., Riva, S. <strong>Two homologous genes, originated by duplication, encode the human hnRNP proteins A2 and A1.</strong> Nucleic Acids Res. 22: 1996-2002, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8029005/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8029005</a>] [<a href="https://doi.org/10.1093/nar/22.11.1996" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8029005">Biamonti et al. (1994)</a> determined that the 36-nucleotide insertion in the B1 transcript arises from inclusion of exon 2. Using Northern blot and RT-PCR analyses, <a href="#9" class="mim-tip-reference" title="Kozu, T., Henrich, B., Schafer, K. P. <strong>Structure and expression of the gene (HNRPA2B1) encoding the human hnRNP protein A2/B1.</strong> Genomics 25: 365-371, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7789969/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7789969</a>] [<a href="https://doi.org/10.1016/0888-7543(95)80035-k" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7789969">Kozu et al. (1995)</a> detected a 1.8-kb transcript representing total A2/B1 mRNA in all 3 human cell lines examined. The levels of B1 expression were about 2 to 5% of total A2/B1 levels in these cell lines. RT-PCR of mouse tissues suggested ubiquitous expression of both A2 and B1 transcripts. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7789969+8029005" 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>Translational repression of glucose transporter-1 (GLUT1, or SLC2A1; <a href="/entry/138140">138140</a>) in glioblastoma multiforme (GBM; <a href="/entry/137800">137800</a>) is mediated by a specific RNA-binding protein that interacts with an AU-rich response element in the 3-prime UTR of the GLUT1 transcript. <a href="#4" class="mim-tip-reference" title="Hamilton, B. J., Nichols, R. C., Tsukamoto, H., Boado, R. J., Pardridge, W. M., Rigby, W. F. C. <strong>hnRNP A2 and hnRNP L bind the 3-prime UTR of glucose transporter 1 mRNA and exist as a complex in vivo.</strong> Biochem. Biophys. Res. Commun. 261: 646-651, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10441480/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10441480</a>] [<a href="https://doi.org/10.1006/bbrc.1999.1040" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10441480">Hamilton et al. (1999)</a> showed that HNRNPA2 and HNRNPL (<a href="/entry/603083">603083</a>) bound the 3-prime UTR of GLUT1 mRNA. Induction of brain ischemia in rats or hypoglycemic stress in 293 cells increased GLUT1 expression via mRNA stability. Polysomes isolated from ischemic rat brains or hypoglycemic 293 cells showed loss of HNRNPA2 and HNRNPL, suggesting that reduced levels of these RNA-binding proteins results in GLUT1 mRNA stability. Immunoprecipitation of polysomes from activated human T lymphocytes suggested that HNRNPA2 and HNRNPL form a complex in vivo. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10441480" 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 pull-down assays and EMSA, <a href="#12" class="mim-tip-reference" title="Moran-Jones, K., Wayman, L., Kennedy, D. D., Reddel, R. R., Sara, S., Snee, M. J., Smith, R. <strong>hnRNP A2, a potential ssDNA/RNA molecular adapter at the telomere.</strong> Nucleic Acids Res. 33: 486-496, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15659580/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15659580</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15659580[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/10.1093/nar/gki203" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15659580">Moran-Jones et al. (2005)</a> identified Hnrnpa2 and Hnrnpa3 (<a href="/entry/605372">605372</a>) as the predominant single-stranded telomere repeat-binding proteins in rat brain. Using rat and human constructs, they identified 2 oligonucleotide-binding sites in HNRNPA2. One site bound single-stranded DNA (ssDNA) with little or no nucleotide sequence preference, whereas the second site bound specific RNA and DNA sequences. The latter site bound single-stranded TTAGGG telomere repeats and a cytoplasmic RNA-trafficking element (A2RE11). Mutation analysis indicated that the tandem RRM domains also bound the telomerase RNA (TERC; <a href="/entry/602322">602322</a>), but the individual RRM domains did not. Full-length HNRNPA2, but not HNRNPA2 truncation mutants, protected telomeric DNA from DNase, suggesting that the glycine-rich domain as well as the RRM domains are required for telomere protection. <a href="#12" class="mim-tip-reference" title="Moran-Jones, K., Wayman, L., Kennedy, D. D., Reddel, R. R., Sara, S., Snee, M. J., Smith, R. <strong>hnRNP A2, a potential ssDNA/RNA molecular adapter at the telomere.</strong> Nucleic Acids Res. 33: 486-496, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15659580/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15659580</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15659580[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/10.1093/nar/gki203" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15659580">Moran-Jones et al. (2005)</a> proposed that HNRNPA2 can potentially bind telomeric DNA repeats and the RNA component of telomerase simultaneously, or that it may bind ssDNA in both sites and act as an intramolecular or intermolecular crosslink. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15659580" 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>DNA-dependent protein kinase (DNAPK; see <a href="/entry/600899">600899</a>) is a multisubunit kinase involved in the repair of DNA double-strand breaks through nonhomologous end-joining. <a href="#5" class="mim-tip-reference" title="Iwanaga, K., Sueoka, N., Sato, A., Hayashi, S., Sueoka, E. <strong>Heterogeneous nuclear ribonucleoprotein B1 protein impairs DNA repair mediated through the inhibition of DNA-dependent protein kinase activity.</strong> Biochem. Biophys. Res. Commun. 333: 888-895, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15964549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15964549</a>] [<a href="https://doi.org/10.1016/j.bbrc.2005.05.180" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15964549">Iwanaga et al. (2005)</a> found that HNRNPB1 interacted directly with the DNAPK subunit Ku70 (XRCC6; <a href="/entry/152690">152690</a>) and inhibited DNAPK activity in a dose-dependent manner in vitro. Knockdown of HNRNPA2B1 in irradiated normal human bronchial epithelial cells reduced HNRNPB1 levels and enhanced recovery of DNA strand breaks compared with controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15964549" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By yeast 2-hybrid analysis of a human brain cDNA library, <a href="#8" class="mim-tip-reference" title="Kosturko, L. D., Maggipinto, M. J., Korza, G., Lee, J. W., Carson, J. H., Barbarese, E. <strong>Heterogeneous nuclear ribonucleoprotein (hnRNP) E1 binds to hnRNP A2 and inhibits translation of A2 response element mRNAs.</strong> Molec. Biol. Cell 17: 3521-3533, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16775011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16775011</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16775011[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/10.1091/mbc.e05-10-0946" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16775011">Kosturko et al. (2006)</a> found that mouse Hnrnpa2 interacted with human HNRNPE1 (PCBP1; <a href="/entry/601209">601209</a>). They confirmed the interaction with in vivo and in vitro protein interaction assays. Hnrnpe1 colocalized with Hnrnpa2 and A2RE mRNA in granules in dendrites of rat oligodendrocytes. Overexpression of HNRNPE1 or microinjection of exogenous HNRNPE1 in rat neural cells inhibited translation of A2RE mRNA, but not translation of mutated A2RE mRNA. Excess HNRNPE1 added to an in vitro translation system reduced translation efficiency of A2RE mRNA in an Hnrnpa2-dependent manner. <a href="#8" class="mim-tip-reference" title="Kosturko, L. D., Maggipinto, M. J., Korza, G., Lee, J. W., Carson, J. H., Barbarese, E. <strong>Heterogeneous nuclear ribonucleoprotein (hnRNP) E1 binds to hnRNP A2 and inhibits translation of A2 response element mRNAs.</strong> Molec. Biol. Cell 17: 3521-3533, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16775011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16775011</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16775011[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/10.1091/mbc.e05-10-0946" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16775011">Kosturko et al. (2006)</a> hypothesized that binding of HNRNPE1 to HNRNPA2 inhibits A2RE mRNA translation during granule transport. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16775011" 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 transgenic fly model of fragile X-associated tremor/ataxia syndrome (FXTAS; <a href="/entry/300623">300623</a>) in which the 5-prime UTR of human FMR1 (<a href="/entry/309550">309550</a>) containing 90 CGG repeats is expressed specifically in the eye results in disorganized ommatidia, depigmentation, and progressive loss of photoreceptor neurons. <a href="#14" class="mim-tip-reference" title="Sofola, O. A., Jin, P., Qin, Y., Duan, R., Liu, H., de Haro, M., Nelson, D. L., Botas, J. <strong>RNA-binding proteins hnRNP A2/B1 and CUGBP1 suppress fragile X CGG premutation repeat-induced neurodegeneration in a Drosophila model of FXTAS.</strong> Neuron 55: 565-571, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17698010/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17698010</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17698010[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.neuron.2007.07.021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17698010">Sofola et al. (2007)</a> found that overexpression of human CUGBP1 (<a href="/entry/601074">601074</a>) suppressed the neurodegenerative eye phenotype in transgenic flies. CUGBP1 did not interact directly with the CGG repeats, but did so via HNRNPA2B1. Expression of the A2 isoform of human HNRNPA2B1, or the Drosophila orthologs, also suppressed the eye phenotype of FXTAS flies. Mouse Hnrnpa2b1 interacted directly with CGG repeat RNA (rCGG) in mouse cerebellar lysates, and increased repeat length increased the binding affinity. The interaction was most evident in cytoplasmic cerebellar lysates. Nuclear Hnrnpa2b1 showed little or no interaction with rCGG repeats, suggesting that protein modification, in either the nuclear or cytoplasmic compartment, affects the interaction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17698010" 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="#11" class="mim-tip-reference" title="Moran-Jones, K., Grindlay, J., Jones, M., Smith, R., Norman, J. C. <strong>hnRNP A2 regulates alternative mRNA splicing of TP53INP2 to control invasive cell migration.</strong> Cancer Res. 69: 9219-9227, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19934309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19934309</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19934309[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/10.1158/0008-5472.CAN-09-1852" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19934309">Moran-Jones et al. (2009)</a> found that HNRNPA2 promoted inclusion of TP53INP2 (<a href="/entry/617549">617549</a>) noncoding exon 2 in A2780 ovarian carcinoma cells, but only when cells were grown in a 3-dimensional substrate. Knockdown of exon 2-containing TP53INP2 transcripts via knockout of HNRNPA2 or via small interfering RNA targeting TP53INP2 exon 2 reduced cell migration through a 3-dimensional gel. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19934309" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="David, C. J., Chen, M., Assanah, M., Canoll, P., Manley, J. L. <strong>HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer.</strong> Nature 463: 364-368, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20010808/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20010808</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20010808[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/nature08697" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20010808">David et al. (2010)</a> showed that 3 hnRNP proteins, polypyrimidine tract-binding protein (PTB, also known as hnRNPI; <a href="/entry/600693">600693</a>), hnRNPA1 (<a href="/entry/164017">164017</a>), and hnRNPA2, bind repressively to sequences flanking exon 9 of the PKM2 gene (<a href="/entry/179050">179050</a>), resulting in exon 10 inclusion and expression of the PKM2 (embryonic) isoform. <a href="#3" class="mim-tip-reference" title="David, C. J., Chen, M., Assanah, M., Canoll, P., Manley, J. L. <strong>HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer.</strong> Nature 463: 364-368, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20010808/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20010808</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20010808[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/nature08697" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20010808">David et al. (2010)</a> also demonstrated that the oncogenic transcription factor c-MYC (<a href="/entry/190080">190080</a>) upregulates transcription of PTB, hnRNPA1, and hnRNPA2, ensuring a high PKM2/PKM1 ratio. Establishing a relevance to cancer, <a href="#3" class="mim-tip-reference" title="David, C. J., Chen, M., Assanah, M., Canoll, P., Manley, J. L. <strong>HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer.</strong> Nature 463: 364-368, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20010808/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20010808</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20010808[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/nature08697" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20010808">David et al. (2010)</a> showed that human gliomas (<a href="/entry/137800">137800</a>) overexpress c-Myc, PTB, hnRNPA1, and hnRNPA2 in a manner that correlates with PKM2 expression. <a href="#3" class="mim-tip-reference" title="David, C. J., Chen, M., Assanah, M., Canoll, P., Manley, J. L. <strong>HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer.</strong> Nature 463: 364-368, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20010808/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20010808</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20010808[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/nature08697" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20010808">David et al. (2010)</a> concluded that their results defined a pathway that regulates an alternative splicing event required for tumor cell proliferation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20010808" 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="Kim, H. J., Kim, N. C., Wang, Y.-D., Scarborough, E. A., Moore, J., Diaz, Z., MacLea, K. S., Freibaum, B., Li, S., Molliex, A., and 25 others. <strong>Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS.</strong> Nature 495: 467-473, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23455423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23455423</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23455423[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/nature11922" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23455423">Kim et al. (2013)</a> reported that HNRNPA2B1 has a C-terminal glycine-rich domain that is essential for activity and mediates interaction with TDP43 (<a href="/entry/605078">605078</a>). This low-complexity domain is predicted to be intrinsically unfolded and has an amino acid composition similar to that of yeast prion domains. Approximately 250 human proteins, including several RNA-binding proteins associated with neurodegenerative disease, harbor a similar distinctive prion-like domain (PrLD) enriched in uncharged polar amino acids and glycine. PrLDs in RNA-binding proteins are essential for the assembly of ribonucleoprotein granules. <a href="#6" class="mim-tip-reference" title="Kim, H. J., Kim, N. C., Wang, Y.-D., Scarborough, E. A., Moore, J., Diaz, Z., MacLea, K. S., Freibaum, B., Li, S., Molliex, A., and 25 others. <strong>Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS.</strong> Nature 495: 467-473, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23455423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23455423</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23455423[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/nature11922" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23455423">Kim et al. (2013)</a> showed that HNRNPA2, the most abundant form of HNRNPA2B1, has an intrinsic tendency to assemble into self-seeding fibrils. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23455423" 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="#16" class="mim-tip-reference" title="Wang, L., Wen, M., Cao, X. <strong>Nuclear hnRNPA2B1 initiates and amplifies the innate immune response to DNA viruses.</strong> Science 365: eaav0758, 2019. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31320558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31320558</a>] [<a href="https://doi.org/10.1126/science.aav0758" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31320558">Wang et al. (2019)</a> reported that HNRNPA2B1 recognizes pathogenic DNA and amplifies interferon-alpha/beta production. Upon DNA virus infection, nuclear-localized HNRNPA2B1 senses viral DNA, homodimerizes, and is then demethylated at arginine-226 by the arginine demethylase JMJD6 (<a href="/entry/604914">604914</a>). This results in HNRNPA2B1 translocation to the cytoplasm, where it activates the TANK-binding kinase-1 (TBK1; <a href="/entry/604834">604834</a>)-interferon regulatory factor-3 (IRF3; <a href="/entry/603734">603734</a>) pathway, leading to IFN-alpha (<a href="/entry/147660">147660</a>)/beta (<a href="/entry/147640">147640</a>) production. Additionally, HNRNPA2B1 facilitates N6-methyladenosine (m6A) modification and nucleocytoplasmic trafficking of CGAS (<a href="/entry/613973">613973</a>), IFI16 (<a href="/entry/147586">147586</a>), and STING (<a href="/entry/612374">612374</a>) mRNAs. This, in turn, amplifies the activation of cytoplasmic TBK1-IRF3 mediated by these factors. <a href="#16" class="mim-tip-reference" title="Wang, L., Wen, M., Cao, X. <strong>Nuclear hnRNPA2B1 initiates and amplifies the innate immune response to DNA viruses.</strong> Science 365: eaav0758, 2019. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31320558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31320558</a>] [<a href="https://doi.org/10.1126/science.aav0758" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31320558">Wang et al. (2019)</a> concluded that HNRNPA2B1 plays important roles in initiating IFN-alpha/beta production and enhancing STING-dependent cytoplasmic antiviral signaling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31320558" 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="#1" class="mim-tip-reference" title="Biamonti, G., Ruggiu, M., Saccone, S., Della Valle, G., Riva, S. <strong>Two homologous genes, originated by duplication, encode the human hnRNP proteins A2 and A1.</strong> Nucleic Acids Res. 22: 1996-2002, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8029005/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8029005</a>] [<a href="https://doi.org/10.1093/nar/22.11.1996" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8029005">Biamonti et al. (1994)</a> determined that the HNRNPA2B1 gene contains 12 exons, including an alternatively spliced 36-nucleotide mini-exon specific for the B1 protein. The intron/exon organization of HNRNPA2B1 is identical to that of the HNRNPA1 gene over its entire length, indicating a common origin by gene duplication. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8029005" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Kozu, T., Henrich, B., Schafer, K. P. <strong>Structure and expression of the gene (HNRPA2B1) encoding the human hnRNP protein A2/B1.</strong> Genomics 25: 365-371, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7789969/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7789969</a>] [<a href="https://doi.org/10.1016/0888-7543(95)80035-k" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7789969">Kozu et al. (1995)</a> determined that the HNRNPA2B1 gene spans over 9 kb. The 5-prime region is GC rich and contains several binding sites for ubiquitous transcription factors, including 7 H4TF1 elements and 2 CCAAT boxes, but no TATA sequence. The 3-prime region contains a pyrimidine-rich RNA degradation motif prior to the polyadenylation signal. Intron 8 contains an Alu repeat that is not found in the HNRNPA1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7789969" 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="#1" class="mim-tip-reference" title="Biamonti, G., Ruggiu, M., Saccone, S., Della Valle, G., Riva, S. <strong>Two homologous genes, originated by duplication, encode the human hnRNP proteins A2 and A1.</strong> Nucleic Acids Res. 22: 1996-2002, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8029005/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8029005</a>] [<a href="https://doi.org/10.1093/nar/22.11.1996" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8029005">Biamonti et al. (1994)</a> mapped the HNRNPA2B1 gene to chromosome 7p15 by fluorescence in situ hybridization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8029005" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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In a family (family 1, previously described by <a href="#15" class="mim-tip-reference" title="Waggoner, B., Kovach, M. J., Winkelman, M., Cai, D., Khardori, R., Gelber, D., Kimonis, V. E. <strong>Heterogeneity in familial dominant Paget disease of bone and muscular dystrophy.</strong> Am. J. Med. Genet. 108: 187-191, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11891683/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11891683</a>] [<a href="https://doi.org/10.1002/ajmg.10199" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11891683">Waggoner et al. (2002)</a>) with dominantly inherited degeneration of muscle, bone, brain, and motor neurons (IBMPFD2; <a href="/entry/615422">615422</a>), <a href="#6" class="mim-tip-reference" title="Kim, H. J., Kim, N. C., Wang, Y.-D., Scarborough, E. A., Moore, J., Diaz, Z., MacLea, K. S., Freibaum, B., Li, S., Molliex, A., and 25 others. <strong>Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS.</strong> Nature 495: 467-473, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23455423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23455423</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23455423[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/nature11922" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23455423">Kim et al. (2013)</a> identified a heterozygous missense mutation in the HNRNPA2B1 gene that altered a conserved aspartic acid at position 290 of the short (A2) isoform and 302 of the long (B1) isoform (D290V; <a href="#0001">600124.0001</a>). <a href="#6" class="mim-tip-reference" title="Kim, H. J., Kim, N. C., Wang, Y.-D., Scarborough, E. A., Moore, J., Diaz, Z., MacLea, K. S., Freibaum, B., Li, S., Molliex, A., and 25 others. <strong>Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS.</strong> Nature 495: 467-473, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23455423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23455423</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23455423[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/nature11922" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23455423">Kim et al. (2013)</a> showed that the intrinsic tendency of HNRNPA2, the most abundant form of HNRNPA2B1, and HNRNPA1 (<a href="/entry/164017">164017</a>) to assemble into self-seeding fibrils is exacerbated by disease mutations. The pathogenic mutations strengthen a 'steric zipper' motif in the prion-like domain (PrLD) that accelerates the formation of self-seeding fibrils that cross-seed polymerization of wildtype HNRNP. Notably, disease mutations promoted excess incorporation of HNRNPA2 and HNRNPA1 into stress granules and drove the formation of cytoplasmic inclusions in animal models that recapitulated the human pathology. <a href="#6" class="mim-tip-reference" title="Kim, H. J., Kim, N. C., Wang, Y.-D., Scarborough, E. A., Moore, J., Diaz, Z., MacLea, K. S., Freibaum, B., Li, S., Molliex, A., and 25 others. <strong>Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS.</strong> Nature 495: 467-473, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23455423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23455423</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23455423[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/nature11922" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23455423">Kim et al. (2013)</a> concluded that dysregulated polymerization caused by a potent mutant steric zipper motif in a PrLD can initiate degenerative disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=23455423+11891683" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By sequencing coding exons of the HNRNPA2B1 gene, <a href="#10" class="mim-tip-reference" title="Le Ber, I., Van Bortel, I., Nicolas, G., Bouya-Ahmed, K., Camuzat, A., Wallon, D., De Septenville, A., Latouche, M., Lattante, S., Kabashi, E., Jornea, L., Hannequin, D., Brice, A., French research Network on FTLD/FTLD-ALS. <strong>hnRNPA2B1 and hnRNPA1 mutations are rare in patients with 'multisystem proteinopathy' and frontotemporal lobar degeneration phenotypes.</strong> Neurobiol. Aging 35: 934.e5-6, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24119545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24119545</a>] [<a href="https://doi.org/10.1016/j.neurobiolaging.2013.09.016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24119545">Le Ber et al. (2014)</a> failed to identify pathogenic mutations in a cohort of 17 unrelated French patients with sporadic or familial occurrence of multiple system proteinopathy manifest as frontotemporal lobar degeneration (FTLD) and/or amyotrophic lateral sclerosis (ALS) that segregated with Paget disease of bone (PDB), and/or inclusion body myositis (IBM). No mutations were found in 60 probands with FTLD or FTLD/ALS. By sequencing the prion-like domain of the HNRNPA2B1 gene, <a href="#13" class="mim-tip-reference" title="Seelen, M., Visser, A. E., Overste, D. J., Kim, H. J., Palud, A., Wong, T. H., van Swieten, J. C., Scheltens, P., Voermans, N. C., Baas, F., de Jong, J. M. B. V., van der Kooi, A. J., de Visser, M., Veldink, J. H., Taylor, J. P., Van Es, M. A., van den Berg, L. H. <strong>No mutations in hnRNPA1 and hnRNPA2B1 in Dutch patients with amyotrophic lateral sclerosis, frontotemporal dementia, and inclusion body myopathy.</strong> Neurobiol. Aging 35: 1956.e9-1956.e11, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24612671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24612671</a>] [<a href="https://doi.org/10.1016/j.neurobiolaging.2014.01.152" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24612671">Seelen et al. (2014)</a> also failed to identify any nonsynonymous mutations in 135 patients with familial ALS, 1,084 patients with sporadic ALS, 68 patients with familial FTLD, 74 patients with sporadic FTLD, and 31 patients with sporadic IBM. A splice site mutation (c.695A-G) was found in 1 patient with familial FTD, but functional studies and segregation analysis were not performed. All patients were from the Netherlands. The findings of both studies suggested that mutations in HNRNPA2B1 are a very rare cause of this spectrum of diseases. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=24119545+24612671" 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>Oculopharyngeal Muscular Dystrophy 2</em></strong></p><p>
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In 11 patients from 10 unrelated families with oculopharyngeal muscular dystrophy-2 (OPMD2; <a href="/entry/620460">620460</a>), <a href="#7" class="mim-tip-reference" title="Kim, H. J., Mohassel, P., Donkervoort, S., Guo, L., O'Donovan, K., Coughlin, M., Lornage, X., Foulds, N., Hammans, S. R., Foley, A. R., Fare, C. M., Ford, A. F., and 46 others. <strong>Heterozygous frameshift variants in HNRNPA2B1 cause early-onset oculopharyngeal muscular dystrophy.</strong> Nature Commun. 13: 2306, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35484142/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35484142</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=35484142[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/s41467-022-30015-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="35484142">Kim et al. (2022)</a> identified heterozygous frameshift mutations in the last coding exon of the HNRNPA2B1 gene that affected both isoforms (see, e.g., <a href="#0002">600124.0002</a>-<a href="#0005">600124.0005</a>). The mutations, which were found by exome sequencing, were not present in the gnomAD database. The mutations occurred de novo in 7 patients and were presumed to be de novo in 2; only 1 family (family 4) showed autosomal dominant inheritance of the mutation. All mutations occurred in the highly conserved M9 nuclear localization signal in the C-terminal LCD domain. The mutations all resulted in the same frameshift with a common C-terminal extension sequence. The mutant mRNAs escaped nonsense-mediated mRNA decay and resulted in the production of novel transcripts and proteins that showed aberrant accumulation in the cytoplasm of cells expressing the mutations. The mutations did not increase the propensity of the HNRNPA2 protein to fibrillize. In vitro studies of some of the mutations showed that they impaired the interaction between HNRNPA2 and its nuclear transport receptor TNPO1 (<a href="/entry/602901">602901</a>), suggesting a loss-of-function effect. However, the mutations caused increased apoptotic cell death in differentiating myoblasts, consistent with a toxic gain-of-function mechanism. The findings added to the growing spectrum of neuromuscular disorders caused by mutations in RNA-binding proteins (RBPs). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35484142" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=600124[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs397515326 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397515326;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=rs397515326" 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=rs397515326" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In affected members of a family (family 1) segregating autosomal dominant inclusion body myopathy with Paget disease of the bone and frontotemporal dementia (IBMPFD2; <a href="/entry/615422">615422</a>), <a href="#6" class="mim-tip-reference" title="Kim, H. J., Kim, N. C., Wang, Y.-D., Scarborough, E. A., Moore, J., Diaz, Z., MacLea, K. S., Freibaum, B., Li, S., Molliex, A., and 25 others. <strong>Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS.</strong> Nature 495: 467-473, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23455423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23455423</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23455423[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/nature11922" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23455423">Kim et al. (2013)</a> identified an 869A-T transversion in the A2 isoform of the HNRNPA2B1 gene (905A-T in the B1 isoform) resulting in an aspartic acid-to-valine substitution at codon 290 (D290V; ASP302VAL, D302V in the B1 isoform). This was the family originally reported by <a href="#15" class="mim-tip-reference" title="Waggoner, B., Kovach, M. J., Winkelman, M., Cai, D., Khardori, R., Gelber, D., Kimonis, V. E. <strong>Heterogeneity in familial dominant Paget disease of bone and muscular dystrophy.</strong> Am. J. Med. Genet. 108: 187-191, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11891683/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11891683</a>] [<a href="https://doi.org/10.1002/ajmg.10199" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11891683">Waggoner et al. (2002)</a>. The aspartic acid at this position is evolutionarily conserved to Drosophila, and is centered in a motif, the prion-like domain (PrLD), that is conserved in multiple human paralogs of the HNRNP A/B family. The mutation segregated with the disease in the family and was not identified in the NHLBI Exome Sequencing Project. In another family with a similar phenotype, <a href="#6" class="mim-tip-reference" title="Kim, H. J., Kim, N. C., Wang, Y.-D., Scarborough, E. A., Moore, J., Diaz, Z., MacLea, K. S., Freibaum, B., Li, S., Molliex, A., and 25 others. <strong>Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS.</strong> Nature 495: 467-473, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23455423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23455423</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23455423[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/nature11922" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23455423">Kim et al. (2013)</a> detected an aspartic acid-to-valine substitution at the analogous residue of HNRNPA1 (<a href="/entry/164017#0001">164017.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11891683+23455423" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a 12-year-old boy (P1) with oculopharyngeal muscular dystrophy-2 (OPMD2; <a href="/entry/620460">620460</a>), <a href="#7" class="mim-tip-reference" title="Kim, H. J., Mohassel, P., Donkervoort, S., Guo, L., O'Donovan, K., Coughlin, M., Lornage, X., Foulds, N., Hammans, S. R., Foley, A. R., Fare, C. M., Ford, A. F., and 46 others. <strong>Heterozygous frameshift variants in HNRNPA2B1 cause early-onset oculopharyngeal muscular dystrophy.</strong> Nature Commun. 13: 2306, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35484142/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35484142</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=35484142[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/s41467-022-30015-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="35484142">Kim et al. (2022)</a> identified a de novo heterozygous 1-bp deletion (c.992delG, NM_002137) in the last coding exon affecting both isoforms of the HNRNPA2B1 gene. The deletion resulted in frameshift and extension of the reading frame (Gly331GlufsTer28). The mutation, which was found by exome sequencing, was not present in the gnomAD database. The mutation occurred in the highly conserved M9 nuclear localization signal in the C-terminal LCD domain. The transcript escaped nonsense-mediated mRNA decay and resulted in the production of a novel protein that showed aberrant accumulation in the cytoplasm of cells expressing the mutation. In vitro studies showed that the variant impaired the interaction between HNRNPA2 and its nuclear transport receptor TNPO1 (<a href="/entry/602901">602901</a>), suggesting a loss-of-function effect. However, the mutation caused increased apoptotic cell death in differentiating myoblasts, consistent with a toxic gain-of-function mechanism. The patient had onset of symptoms at 2 years of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35484142" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a 17-year-old boy (P2) with oculopharyngeal muscular dystrophy-2 (OPMD2; <a href="/entry/620460">620460</a>), <a href="#7" class="mim-tip-reference" title="Kim, H. J., Mohassel, P., Donkervoort, S., Guo, L., O'Donovan, K., Coughlin, M., Lornage, X., Foulds, N., Hammans, S. R., Foley, A. R., Fare, C. M., Ford, A. F., and 46 others. <strong>Heterozygous frameshift variants in HNRNPA2B1 cause early-onset oculopharyngeal muscular dystrophy.</strong> Nature Commun. 13: 2306, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35484142/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35484142</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=35484142[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/s41467-022-30015-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="35484142">Kim et al. (2022)</a> identified a de novo heterozygous 1-bp deletion (c.981delA, NM_002137) in the last coding exon affecting both isoforms of the HNRNPA2B1 gene. The deletion resulted in frameshift and extension of the reading frame (Gly328AlafsTer31). The mutation, which was found by exome sequencing, was not present in the gnomAD database. The mutation occurred in the highly conserved M9 nuclear localization signal in the C-terminal LCD domain. The transcript escaped nonsense-mediated mRNA decay and resulted in the production of a novel protein that showed aberrant accumulation in the cytoplasm of cells expressing the mutation. In vitro studies showed that the variant impaired the interaction between HNRNPA2 and its nuclear transport receptor TNPO1 (<a href="/entry/602901">602901</a>), suggesting a loss-of-function effect. However, the mutation caused increased apoptotic cell death in differentiating myoblasts, consistent with a toxic gain-of-function mechanism. The patient had onset of symptoms at 5 years of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35484142" 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 OCULOPHARYNGEAL MUSCULAR DYSTROPHY 2</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV003319292" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV003319292" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV003319292</a>
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<p>In 2 sisters (family 4, P4 and P5) with oculopharyngeal muscular dystrophy-2 (OPMD2; <a href="/entry/620460">620460</a>), <a href="#7" class="mim-tip-reference" title="Kim, H. J., Mohassel, P., Donkervoort, S., Guo, L., O'Donovan, K., Coughlin, M., Lornage, X., Foulds, N., Hammans, S. R., Foley, A. R., Fare, C. M., Ford, A. F., and 46 others. <strong>Heterozygous frameshift variants in HNRNPA2B1 cause early-onset oculopharyngeal muscular dystrophy.</strong> Nature Commun. 13: 2306, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35484142/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35484142</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=35484142[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/s41467-022-30015-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="35484142">Kim et al. (2022)</a> identified a heterozygous 1-bp deletion (c.966delA, NM_002137) in the last coding exon affecting both isoforms of the HNRNPA2B1 gene. The deletion resulted in frameshift and extension of the reading frame (Asn323ThrfsTer36). The mutation, which was found by exome sequencing, was not present in the gnomAD database. The mutation occurred in the highly conserved M9 nuclear localization signal in the C-terminal LCD domain. The transcript escaped nonsense-mediated mRNA decay and resulted in the production of a novel protein that showed aberrant accumulation in the cytoplasm of cells expressing the mutation. In vitro studies showed that the variant impaired the interaction between HNRNPA2 and its nuclear transport receptor TNPO1 (<a href="/entry/602901">602901</a>), suggesting a loss-of-function effect. However, the mutation caused increased apoptotic cell death in differentiating myoblasts, consistent with a toxic gain-of-function mechanism. The patients had onset of symptoms in their late teens. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35484142" 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="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV003319293 OR RCV003581923 OR RCV004587484" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV003319293, RCV003581923, RCV004587484" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV003319293...</a>
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<p>In 2 unrelated girls (P7 and P10) with oculopharyngeal muscular dystrophy-2 (OPMD2; <a href="/entry/620460">620460</a>), <a href="#7" class="mim-tip-reference" title="Kim, H. J., Mohassel, P., Donkervoort, S., Guo, L., O'Donovan, K., Coughlin, M., Lornage, X., Foulds, N., Hammans, S. R., Foley, A. R., Fare, C. M., Ford, A. F., and 46 others. <strong>Heterozygous frameshift variants in HNRNPA2B1 cause early-onset oculopharyngeal muscular dystrophy.</strong> Nature Commun. 13: 2306, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35484142/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35484142</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=35484142[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/s41467-022-30015-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="35484142">Kim et al. (2022)</a> identified a de novo heterozygous 2-bp duplication (c.996_997dupTG, NM_002137) in the last coding exon affecting both isoforms of the HNRNPA2B1 gene. The duplication resulted in frameshift and extension of the reading frame (Gly333ValfsTer27). The mutation, which was found by exome sequencing, was not present in the gnomAD database. The mutation occurred in the highly conserved M9 nuclear localization signal in the C-terminal LCD domain and was predicted to escape nonsense-mediated mRNA decay. Both patients had a severe form of the disorder with onset of symptoms in infancy or early childhood, respiratory insufficiency, dysphagia requiring tube-feeding, and loss of independent ambulation in the first decade. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35484142" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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Biamonti, G., Ruggiu, M., Saccone, S., Della Valle, G., Riva, S.
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<strong>Two homologous genes, originated by duplication, encode the human hnRNP proteins A2 and A1.</strong>
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[<a href="https://doi.org/10.1093/nar/22.11.1996" target="_blank">Full Text</a>]
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Burd, C. G., Swanson, M. S., Gorlach, M., Dreyfuss, G.
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[<a href="https://doi.org/10.1073/pnas.86.24.9788" target="_blank">Full Text</a>]
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David, C. J., Chen, M., Assanah, M., Canoll, P., Manley, J. L.
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<strong>HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer.</strong>
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Nature 463: 364-368, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20010808/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20010808</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20010808[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=20010808" 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/nature08697" target="_blank">Full Text</a>]
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Hamilton, B. J., Nichols, R. C., Tsukamoto, H., Boado, R. J., Pardridge, W. M., Rigby, W. F. C.
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<strong>hnRNP A2 and hnRNP L bind the 3-prime UTR of glucose transporter 1 mRNA and exist as a complex in vivo.</strong>
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Biochem. Biophys. Res. Commun. 261: 646-651, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10441480/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10441480</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10441480" 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/bbrc.1999.1040" target="_blank">Full Text</a>]
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Iwanaga, K., Sueoka, N., Sato, A., Hayashi, S., Sueoka, E.
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<strong>Heterogeneous nuclear ribonucleoprotein B1 protein impairs DNA repair mediated through the inhibition of DNA-dependent protein kinase activity.</strong>
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Biochem. Biophys. Res. Commun. 333: 888-895, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15964549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15964549</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15964549" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Kim, H. J., Kim, N. C., Wang, Y.-D., Scarborough, E. A., Moore, J., Diaz, Z., MacLea, K. S., Freibaum, B., Li, S., Molliex, A., and 25 others.
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<strong>Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS.</strong>
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Nature 495: 467-473, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23455423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23455423</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23455423[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=23455423" 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/nature11922" target="_blank">Full Text</a>]
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Kim, H. J., Mohassel, P., Donkervoort, S., Guo, L., O'Donovan, K., Coughlin, M., Lornage, X., Foulds, N., Hammans, S. R., Foley, A. R., Fare, C. M., Ford, A. F., and 46 others.
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<strong>Heterozygous frameshift variants in HNRNPA2B1 cause early-onset oculopharyngeal muscular dystrophy.</strong>
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Nature Commun. 13: 2306, 2022.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35484142/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35484142</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=35484142[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=35484142" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/s41467-022-30015-1" target="_blank">Full Text</a>]
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Kosturko, L. D., Maggipinto, M. J., Korza, G., Lee, J. W., Carson, J. H., Barbarese, E.
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<strong>Heterogeneous nuclear ribonucleoprotein (hnRNP) E1 binds to hnRNP A2 and inhibits translation of A2 response element mRNAs.</strong>
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Molec. Biol. Cell 17: 3521-3533, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16775011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16775011</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16775011[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=16775011" 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/10.1091/mbc.e05-10-0946" target="_blank">Full Text</a>]
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<a id="Kozu1995" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Kozu, T., Henrich, B., Schafer, K. P.
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<strong>Structure and expression of the gene (HNRPA2B1) encoding the human hnRNP protein A2/B1.</strong>
|
|
Genomics 25: 365-371, 1995.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7789969/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7789969</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7789969" 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/10.1016/0888-7543(95)80035-k" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="10" class="mim-anchor"></a>
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<a id="Le Ber2014" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Le Ber, I., Van Bortel, I., Nicolas, G., Bouya-Ahmed, K., Camuzat, A., Wallon, D., De Septenville, A., Latouche, M., Lattante, S., Kabashi, E., Jornea, L., Hannequin, D., Brice, A., French research Network on FTLD/FTLD-ALS.
|
|
<strong>hnRNPA2B1 and hnRNPA1 mutations are rare in patients with 'multisystem proteinopathy' and frontotemporal lobar degeneration phenotypes.</strong>
|
|
Neurobiol. Aging 35: 934.e5-6, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24119545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24119545</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24119545" 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.neurobiolaging.2013.09.016" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="11" class="mim-anchor"></a>
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<a id="Moran-Jones2009" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
|
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Moran-Jones, K., Grindlay, J., Jones, M., Smith, R., Norman, J. C.
|
|
<strong>hnRNP A2 regulates alternative mRNA splicing of TP53INP2 to control invasive cell migration.</strong>
|
|
Cancer Res. 69: 9219-9227, 2009.
|
|
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19934309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19934309</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19934309[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=19934309" 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/10.1158/0008-5472.CAN-09-1852" 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="12" class="mim-anchor"></a>
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<a id="Moran-Jones2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Moran-Jones, K., Wayman, L., Kennedy, D. D., Reddel, R. R., Sara, S., Snee, M. J., Smith, R.
|
|
<strong>hnRNP A2, a potential ssDNA/RNA molecular adapter at the telomere.</strong>
|
|
Nucleic Acids Res. 33: 486-496, 2005.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15659580/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15659580</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15659580[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=15659580" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/nar/gki203" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="13" class="mim-anchor"></a>
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<a id="Seelen1956" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Seelen, M., Visser, A. E., Overste, D. J., Kim, H. J., Palud, A., Wong, T. H., van Swieten, J. C., Scheltens, P., Voermans, N. C., Baas, F., de Jong, J. M. B. V., van der Kooi, A. J., de Visser, M., Veldink, J. H., Taylor, J. P., Van Es, M. A., van den Berg, L. H.
|
|
<strong>No mutations in hnRNPA1 and hnRNPA2B1 in Dutch patients with amyotrophic lateral sclerosis, frontotemporal dementia, and inclusion body myopathy.</strong>
|
|
Neurobiol. Aging 35: 1956.e9-1956.e11, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24612671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24612671</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24612671" 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.neurobiolaging.2014.01.152" 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="14" class="mim-anchor"></a>
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<a id="Sofola2007" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Sofola, O. A., Jin, P., Qin, Y., Duan, R., Liu, H., de Haro, M., Nelson, D. L., Botas, J.
|
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<strong>RNA-binding proteins hnRNP A2/B1 and CUGBP1 suppress fragile X CGG premutation repeat-induced neurodegeneration in a Drosophila model of FXTAS.</strong>
|
|
Neuron 55: 565-571, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17698010/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17698010</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17698010[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=17698010" 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.neuron.2007.07.021" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="15" class="mim-anchor"></a>
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<a id="Waggoner2002" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Waggoner, B., Kovach, M. J., Winkelman, M., Cai, D., Khardori, R., Gelber, D., Kimonis, V. E.
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<strong>Heterogeneity in familial dominant Paget disease of bone and muscular dystrophy.</strong>
|
|
Am. J. Med. Genet. 108: 187-191, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11891683/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11891683</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11891683" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.10199" 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="16" class="mim-anchor"></a>
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<a id="Wang2019" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wang, L., Wen, M., Cao, X.
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<strong>Nuclear hnRNPA2B1 initiates and amplifies the innate immune response to DNA viruses.</strong>
|
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Science 365: eaav0758, 2019. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31320558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31320558</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31320558" 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.aav0758" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 08/02/2023
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
|
|
Ada Hamosh - updated : 12/20/2019<br>Patricia A. Hartz - updated : 06/22/2017<br>Cassandra L. Kniffin - updated : 7/29/2015<br>Ada Hamosh - updated : 9/24/2013<br>Ada Hamosh - updated : 2/18/2010<br>Patricia A. Hartz - updated : 9/10/2009<br>Alan F. Scott - edited : 12/9/1996
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
|
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
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<span class="text-nowrap mim-text-font">
|
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Creation Date:
|
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</span>
|
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</div>
|
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
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Victor A. McKusick : 9/22/1994
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="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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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
|
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 08/07/2023
|
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</span>
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</div>
|
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</div>
|
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<div class="row collapse" id="mimCollapseEditHistory">
|
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
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alopez : 08/03/2023<br>ckniffin : 08/02/2023<br>alopez : 12/20/2019<br>mgross : 06/22/2017<br>carol : 07/30/2015<br>mcolton : 7/29/2015<br>ckniffin : 7/29/2015<br>alopez : 3/30/2015<br>alopez : 1/15/2014<br>alopez : 10/18/2013<br>alopez : 9/24/2013<br>alopez : 2/24/2010<br>terry : 2/18/2010<br>mgross : 9/17/2009<br>mgross : 9/17/2009<br>terry : 9/10/2009<br>wwang : 8/27/2008<br>alopez : 6/10/2005<br>alopez : 6/13/1997<br>mark : 12/9/1996<br>mark : 12/9/1996<br>mark : 2/2/1996<br>mark : 5/19/1995<br>carol : 10/13/1994<br>carol : 9/22/1994
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
|
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<strong>*</strong> 600124
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</span>
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</h3>
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</div>
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<div>
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<h3>
|
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<span class="mim-font">
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HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN A2/B1; HNRNPA2B1
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
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HNRPA2B1
|
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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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<p>
|
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<span class="mim-font">
|
|
Other entities represented in this entry:
|
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</span>
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</p>
|
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</div>
|
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<div>
|
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<span class="h3 mim-font">
|
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HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN A2, INCLUDED; HNRPA2, INCLUDED
|
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</span>
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</div>
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<div>
|
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<span class="h4 mim-font">
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HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN B1, INCLUDED; HNRPB1, INCLUDED
|
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</span>
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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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<p>
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<span class="mim-text-font">
|
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<strong><em>HGNC Approved Gene Symbol: HNRNPA2B1</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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<p>
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: 7p15.2
|
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|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 7:26,189,927-26,200,746 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
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</p>
|
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</div>
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<div>
|
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</h4>
|
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<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
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<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
7p15.2
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
?Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
615422
|
|
</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
3
|
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</span>
|
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</td>
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</tr>
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<tr>
|
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<td>
|
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<span class="mim-font">
|
|
Oculopharyngeal muscular dystrophy 2
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620460
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Autosomal dominant
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<span class="mim-font">
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3
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<strong>TEXT</strong>
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<strong>Description</strong>
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<p>The HNRNPA2B1 gene encodes 2 major proteins, HNRNPA2 and HNRNPB1, through alternative splicing. HNRNPA/B proteins, such as HNRNPA2 and HNRNPB1, are involved in packaging nascent mRNA, in alternative splicing, and in cytoplasmic RNA trafficking, translation, and stabilization. HNRNPA2 and HNRNPB1 also appear to function in telomere maintenance, cell proliferation and differentiation, and glucose transport (Moran-Jones et al., 2005; Iwanaga et al., 2005). </p>
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<strong>Cloning and Expression</strong>
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<p>By immunoscreening a HeLa cell cDNA expression library using mouse anti-A2 and anti-B1 antibodies, followed by screening a human osteosarcoma cDNA library, Burd et al. (1989) obtained full-length A2 and B1 clones. The B1 cDNA has a 36-nucleotide insertion near its 5-prime end relative to A2, but they are otherwise identical. The deduced A2 protein contains 341 amino acids, and the deduced B1 protein contains an in-frame 12-amino acid insert after glu2 compared with A2. Both proteins contain 2 consensus-type RNA-binding domains, followed by an extended C-terminal glycine-rich region. The insert in B1 introduces a putative nuclear localization signal. In vitro translation produced A2 and B1 proteins that comigrated with purified endogenous HeLa cell A2 and B1 at apparent molecular masses of 36 and 38 kD, respectively. </p><p>Biamonti et al. (1994) and Kozu et al. (1995) independently cloned HNRNPA2B1. Biamonti et al. (1994) determined that the 36-nucleotide insertion in the B1 transcript arises from inclusion of exon 2. Using Northern blot and RT-PCR analyses, Kozu et al. (1995) detected a 1.8-kb transcript representing total A2/B1 mRNA in all 3 human cell lines examined. The levels of B1 expression were about 2 to 5% of total A2/B1 levels in these cell lines. RT-PCR of mouse tissues suggested ubiquitous expression of both A2 and B1 transcripts. </p>
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<strong>Gene Function</strong>
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<p>Translational repression of glucose transporter-1 (GLUT1, or SLC2A1; 138140) in glioblastoma multiforme (GBM; 137800) is mediated by a specific RNA-binding protein that interacts with an AU-rich response element in the 3-prime UTR of the GLUT1 transcript. Hamilton et al. (1999) showed that HNRNPA2 and HNRNPL (603083) bound the 3-prime UTR of GLUT1 mRNA. Induction of brain ischemia in rats or hypoglycemic stress in 293 cells increased GLUT1 expression via mRNA stability. Polysomes isolated from ischemic rat brains or hypoglycemic 293 cells showed loss of HNRNPA2 and HNRNPL, suggesting that reduced levels of these RNA-binding proteins results in GLUT1 mRNA stability. Immunoprecipitation of polysomes from activated human T lymphocytes suggested that HNRNPA2 and HNRNPL form a complex in vivo. </p><p>Using pull-down assays and EMSA, Moran-Jones et al. (2005) identified Hnrnpa2 and Hnrnpa3 (605372) as the predominant single-stranded telomere repeat-binding proteins in rat brain. Using rat and human constructs, they identified 2 oligonucleotide-binding sites in HNRNPA2. One site bound single-stranded DNA (ssDNA) with little or no nucleotide sequence preference, whereas the second site bound specific RNA and DNA sequences. The latter site bound single-stranded TTAGGG telomere repeats and a cytoplasmic RNA-trafficking element (A2RE11). Mutation analysis indicated that the tandem RRM domains also bound the telomerase RNA (TERC; 602322), but the individual RRM domains did not. Full-length HNRNPA2, but not HNRNPA2 truncation mutants, protected telomeric DNA from DNase, suggesting that the glycine-rich domain as well as the RRM domains are required for telomere protection. Moran-Jones et al. (2005) proposed that HNRNPA2 can potentially bind telomeric DNA repeats and the RNA component of telomerase simultaneously, or that it may bind ssDNA in both sites and act as an intramolecular or intermolecular crosslink. </p><p>DNA-dependent protein kinase (DNAPK; see 600899) is a multisubunit kinase involved in the repair of DNA double-strand breaks through nonhomologous end-joining. Iwanaga et al. (2005) found that HNRNPB1 interacted directly with the DNAPK subunit Ku70 (XRCC6; 152690) and inhibited DNAPK activity in a dose-dependent manner in vitro. Knockdown of HNRNPA2B1 in irradiated normal human bronchial epithelial cells reduced HNRNPB1 levels and enhanced recovery of DNA strand breaks compared with controls. </p><p>By yeast 2-hybrid analysis of a human brain cDNA library, Kosturko et al. (2006) found that mouse Hnrnpa2 interacted with human HNRNPE1 (PCBP1; 601209). They confirmed the interaction with in vivo and in vitro protein interaction assays. Hnrnpe1 colocalized with Hnrnpa2 and A2RE mRNA in granules in dendrites of rat oligodendrocytes. Overexpression of HNRNPE1 or microinjection of exogenous HNRNPE1 in rat neural cells inhibited translation of A2RE mRNA, but not translation of mutated A2RE mRNA. Excess HNRNPE1 added to an in vitro translation system reduced translation efficiency of A2RE mRNA in an Hnrnpa2-dependent manner. Kosturko et al. (2006) hypothesized that binding of HNRNPE1 to HNRNPA2 inhibits A2RE mRNA translation during granule transport. </p><p>A transgenic fly model of fragile X-associated tremor/ataxia syndrome (FXTAS; 300623) in which the 5-prime UTR of human FMR1 (309550) containing 90 CGG repeats is expressed specifically in the eye results in disorganized ommatidia, depigmentation, and progressive loss of photoreceptor neurons. Sofola et al. (2007) found that overexpression of human CUGBP1 (601074) suppressed the neurodegenerative eye phenotype in transgenic flies. CUGBP1 did not interact directly with the CGG repeats, but did so via HNRNPA2B1. Expression of the A2 isoform of human HNRNPA2B1, or the Drosophila orthologs, also suppressed the eye phenotype of FXTAS flies. Mouse Hnrnpa2b1 interacted directly with CGG repeat RNA (rCGG) in mouse cerebellar lysates, and increased repeat length increased the binding affinity. The interaction was most evident in cytoplasmic cerebellar lysates. Nuclear Hnrnpa2b1 showed little or no interaction with rCGG repeats, suggesting that protein modification, in either the nuclear or cytoplasmic compartment, affects the interaction. </p><p>Moran-Jones et al. (2009) found that HNRNPA2 promoted inclusion of TP53INP2 (617549) noncoding exon 2 in A2780 ovarian carcinoma cells, but only when cells were grown in a 3-dimensional substrate. Knockdown of exon 2-containing TP53INP2 transcripts via knockout of HNRNPA2 or via small interfering RNA targeting TP53INP2 exon 2 reduced cell migration through a 3-dimensional gel. </p><p>David et al. (2010) showed that 3 hnRNP proteins, polypyrimidine tract-binding protein (PTB, also known as hnRNPI; 600693), hnRNPA1 (164017), and hnRNPA2, bind repressively to sequences flanking exon 9 of the PKM2 gene (179050), resulting in exon 10 inclusion and expression of the PKM2 (embryonic) isoform. David et al. (2010) also demonstrated that the oncogenic transcription factor c-MYC (190080) upregulates transcription of PTB, hnRNPA1, and hnRNPA2, ensuring a high PKM2/PKM1 ratio. Establishing a relevance to cancer, David et al. (2010) showed that human gliomas (137800) overexpress c-Myc, PTB, hnRNPA1, and hnRNPA2 in a manner that correlates with PKM2 expression. David et al. (2010) concluded that their results defined a pathway that regulates an alternative splicing event required for tumor cell proliferation. </p><p>Kim et al. (2013) reported that HNRNPA2B1 has a C-terminal glycine-rich domain that is essential for activity and mediates interaction with TDP43 (605078). This low-complexity domain is predicted to be intrinsically unfolded and has an amino acid composition similar to that of yeast prion domains. Approximately 250 human proteins, including several RNA-binding proteins associated with neurodegenerative disease, harbor a similar distinctive prion-like domain (PrLD) enriched in uncharged polar amino acids and glycine. PrLDs in RNA-binding proteins are essential for the assembly of ribonucleoprotein granules. Kim et al. (2013) showed that HNRNPA2, the most abundant form of HNRNPA2B1, has an intrinsic tendency to assemble into self-seeding fibrils. </p><p>Wang et al. (2019) reported that HNRNPA2B1 recognizes pathogenic DNA and amplifies interferon-alpha/beta production. Upon DNA virus infection, nuclear-localized HNRNPA2B1 senses viral DNA, homodimerizes, and is then demethylated at arginine-226 by the arginine demethylase JMJD6 (604914). This results in HNRNPA2B1 translocation to the cytoplasm, where it activates the TANK-binding kinase-1 (TBK1; 604834)-interferon regulatory factor-3 (IRF3; 603734) pathway, leading to IFN-alpha (147660)/beta (147640) production. Additionally, HNRNPA2B1 facilitates N6-methyladenosine (m6A) modification and nucleocytoplasmic trafficking of CGAS (613973), IFI16 (147586), and STING (612374) mRNAs. This, in turn, amplifies the activation of cytoplasmic TBK1-IRF3 mediated by these factors. Wang et al. (2019) concluded that HNRNPA2B1 plays important roles in initiating IFN-alpha/beta production and enhancing STING-dependent cytoplasmic antiviral signaling. </p>
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<strong>Gene Structure</strong>
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<p>Biamonti et al. (1994) determined that the HNRNPA2B1 gene contains 12 exons, including an alternatively spliced 36-nucleotide mini-exon specific for the B1 protein. The intron/exon organization of HNRNPA2B1 is identical to that of the HNRNPA1 gene over its entire length, indicating a common origin by gene duplication. </p><p>Kozu et al. (1995) determined that the HNRNPA2B1 gene spans over 9 kb. The 5-prime region is GC rich and contains several binding sites for ubiquitous transcription factors, including 7 H4TF1 elements and 2 CCAAT boxes, but no TATA sequence. The 3-prime region contains a pyrimidine-rich RNA degradation motif prior to the polyadenylation signal. Intron 8 contains an Alu repeat that is not found in the HNRNPA1 gene. </p>
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<strong>Mapping</strong>
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<p>Biamonti et al. (1994) mapped the HNRNPA2B1 gene to chromosome 7p15 by fluorescence in situ hybridization. </p>
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<strong>Molecular Genetics</strong>
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<p><strong><em>Inclusion Body Myopathy With Early-Onset Paget Disease And Frontotemporal Dementia 2</em></strong></p><p>
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In a family (family 1, previously described by Waggoner et al. (2002)) with dominantly inherited degeneration of muscle, bone, brain, and motor neurons (IBMPFD2; 615422), Kim et al. (2013) identified a heterozygous missense mutation in the HNRNPA2B1 gene that altered a conserved aspartic acid at position 290 of the short (A2) isoform and 302 of the long (B1) isoform (D290V; 600124.0001). Kim et al. (2013) showed that the intrinsic tendency of HNRNPA2, the most abundant form of HNRNPA2B1, and HNRNPA1 (164017) to assemble into self-seeding fibrils is exacerbated by disease mutations. The pathogenic mutations strengthen a 'steric zipper' motif in the prion-like domain (PrLD) that accelerates the formation of self-seeding fibrils that cross-seed polymerization of wildtype HNRNP. Notably, disease mutations promoted excess incorporation of HNRNPA2 and HNRNPA1 into stress granules and drove the formation of cytoplasmic inclusions in animal models that recapitulated the human pathology. Kim et al. (2013) concluded that dysregulated polymerization caused by a potent mutant steric zipper motif in a PrLD can initiate degenerative disease. </p><p>By sequencing coding exons of the HNRNPA2B1 gene, Le Ber et al. (2014) failed to identify pathogenic mutations in a cohort of 17 unrelated French patients with sporadic or familial occurrence of multiple system proteinopathy manifest as frontotemporal lobar degeneration (FTLD) and/or amyotrophic lateral sclerosis (ALS) that segregated with Paget disease of bone (PDB), and/or inclusion body myositis (IBM). No mutations were found in 60 probands with FTLD or FTLD/ALS. By sequencing the prion-like domain of the HNRNPA2B1 gene, Seelen et al. (2014) also failed to identify any nonsynonymous mutations in 135 patients with familial ALS, 1,084 patients with sporadic ALS, 68 patients with familial FTLD, 74 patients with sporadic FTLD, and 31 patients with sporadic IBM. A splice site mutation (c.695A-G) was found in 1 patient with familial FTD, but functional studies and segregation analysis were not performed. All patients were from the Netherlands. The findings of both studies suggested that mutations in HNRNPA2B1 are a very rare cause of this spectrum of diseases. </p><p><strong><em>Oculopharyngeal Muscular Dystrophy 2</em></strong></p><p>
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In 11 patients from 10 unrelated families with oculopharyngeal muscular dystrophy-2 (OPMD2; 620460), Kim et al. (2022) identified heterozygous frameshift mutations in the last coding exon of the HNRNPA2B1 gene that affected both isoforms (see, e.g., 600124.0002-600124.0005). The mutations, which were found by exome sequencing, were not present in the gnomAD database. The mutations occurred de novo in 7 patients and were presumed to be de novo in 2; only 1 family (family 4) showed autosomal dominant inheritance of the mutation. All mutations occurred in the highly conserved M9 nuclear localization signal in the C-terminal LCD domain. The mutations all resulted in the same frameshift with a common C-terminal extension sequence. The mutant mRNAs escaped nonsense-mediated mRNA decay and resulted in the production of novel transcripts and proteins that showed aberrant accumulation in the cytoplasm of cells expressing the mutations. The mutations did not increase the propensity of the HNRNPA2 protein to fibrillize. In vitro studies of some of the mutations showed that they impaired the interaction between HNRNPA2 and its nuclear transport receptor TNPO1 (602901), suggesting a loss-of-function effect. However, the mutations caused increased apoptotic cell death in differentiating myoblasts, consistent with a toxic gain-of-function mechanism. The findings added to the growing spectrum of neuromuscular disorders caused by mutations in RNA-binding proteins (RBPs). </p>
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<strong>ALLELIC VARIANTS</strong>
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<strong>5 Selected Examples):</strong>
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<strong>.0001 INCLUSION BODY MYOPATHY WITH EARLY-ONSET PAGET DISEASE AND FRONTOTEMPORAL DEMENTIA 2 (1 family)</strong>
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HNRNPA2B1, ASP290VAL
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SNP: rs397515326,
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ClinVar: RCV000055652
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<p>In affected members of a family (family 1) segregating autosomal dominant inclusion body myopathy with Paget disease of the bone and frontotemporal dementia (IBMPFD2; 615422), Kim et al. (2013) identified an 869A-T transversion in the A2 isoform of the HNRNPA2B1 gene (905A-T in the B1 isoform) resulting in an aspartic acid-to-valine substitution at codon 290 (D290V; ASP302VAL, D302V in the B1 isoform). This was the family originally reported by Waggoner et al. (2002). The aspartic acid at this position is evolutionarily conserved to Drosophila, and is centered in a motif, the prion-like domain (PrLD), that is conserved in multiple human paralogs of the HNRNP A/B family. The mutation segregated with the disease in the family and was not identified in the NHLBI Exome Sequencing Project. In another family with a similar phenotype, Kim et al. (2013) detected an aspartic acid-to-valine substitution at the analogous residue of HNRNPA1 (164017.0001). </p>
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<strong>.0002 OCULOPHARYNGEAL MUSCULAR DYSTROPHY 2</strong>
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HNRNPA2B1, 1-BP DEL, 992G
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ClinVar: RCV003319290
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<p>In a 12-year-old boy (P1) with oculopharyngeal muscular dystrophy-2 (OPMD2; 620460), Kim et al. (2022) identified a de novo heterozygous 1-bp deletion (c.992delG, NM_002137) in the last coding exon affecting both isoforms of the HNRNPA2B1 gene. The deletion resulted in frameshift and extension of the reading frame (Gly331GlufsTer28). The mutation, which was found by exome sequencing, was not present in the gnomAD database. The mutation occurred in the highly conserved M9 nuclear localization signal in the C-terminal LCD domain. The transcript escaped nonsense-mediated mRNA decay and resulted in the production of a novel protein that showed aberrant accumulation in the cytoplasm of cells expressing the mutation. In vitro studies showed that the variant impaired the interaction between HNRNPA2 and its nuclear transport receptor TNPO1 (602901), suggesting a loss-of-function effect. However, the mutation caused increased apoptotic cell death in differentiating myoblasts, consistent with a toxic gain-of-function mechanism. The patient had onset of symptoms at 2 years of age. </p>
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<strong>.0003 OCULOPHARYNGEAL MUSCULAR DYSTROPHY 2</strong>
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HNRNPA2B1, 1-BP DEL, 981A
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ClinVar: RCV003319291
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<p>In a 17-year-old boy (P2) with oculopharyngeal muscular dystrophy-2 (OPMD2; 620460), Kim et al. (2022) identified a de novo heterozygous 1-bp deletion (c.981delA, NM_002137) in the last coding exon affecting both isoforms of the HNRNPA2B1 gene. The deletion resulted in frameshift and extension of the reading frame (Gly328AlafsTer31). The mutation, which was found by exome sequencing, was not present in the gnomAD database. The mutation occurred in the highly conserved M9 nuclear localization signal in the C-terminal LCD domain. The transcript escaped nonsense-mediated mRNA decay and resulted in the production of a novel protein that showed aberrant accumulation in the cytoplasm of cells expressing the mutation. In vitro studies showed that the variant impaired the interaction between HNRNPA2 and its nuclear transport receptor TNPO1 (602901), suggesting a loss-of-function effect. However, the mutation caused increased apoptotic cell death in differentiating myoblasts, consistent with a toxic gain-of-function mechanism. The patient had onset of symptoms at 5 years of age. </p>
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<strong>.0004 OCULOPHARYNGEAL MUSCULAR DYSTROPHY 2</strong>
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HNRNPA2B1, 1-BP DEL, 966A
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ClinVar: RCV003319292
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<p>In 2 sisters (family 4, P4 and P5) with oculopharyngeal muscular dystrophy-2 (OPMD2; 620460), Kim et al. (2022) identified a heterozygous 1-bp deletion (c.966delA, NM_002137) in the last coding exon affecting both isoforms of the HNRNPA2B1 gene. The deletion resulted in frameshift and extension of the reading frame (Asn323ThrfsTer36). The mutation, which was found by exome sequencing, was not present in the gnomAD database. The mutation occurred in the highly conserved M9 nuclear localization signal in the C-terminal LCD domain. The transcript escaped nonsense-mediated mRNA decay and resulted in the production of a novel protein that showed aberrant accumulation in the cytoplasm of cells expressing the mutation. In vitro studies showed that the variant impaired the interaction between HNRNPA2 and its nuclear transport receptor TNPO1 (602901), suggesting a loss-of-function effect. However, the mutation caused increased apoptotic cell death in differentiating myoblasts, consistent with a toxic gain-of-function mechanism. The patients had onset of symptoms in their late teens. </p>
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<span class="mim-font">
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<strong>.0005 OCULOPHARYNGEAL MUSCULAR DYSTROPHY 2</strong>
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HNRNPA2B1, 2-BP DUP, 996TG
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<br />
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ClinVar: RCV003319293, RCV003581923, RCV004587484
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<p>In 2 unrelated girls (P7 and P10) with oculopharyngeal muscular dystrophy-2 (OPMD2; 620460), Kim et al. (2022) identified a de novo heterozygous 2-bp duplication (c.996_997dupTG, NM_002137) in the last coding exon affecting both isoforms of the HNRNPA2B1 gene. The duplication resulted in frameshift and extension of the reading frame (Gly333ValfsTer27). The mutation, which was found by exome sequencing, was not present in the gnomAD database. The mutation occurred in the highly conserved M9 nuclear localization signal in the C-terminal LCD domain and was predicted to escape nonsense-mediated mRNA decay. Both patients had a severe form of the disorder with onset of symptoms in infancy or early childhood, respiratory insufficiency, dysphagia requiring tube-feeding, and loss of independent ambulation in the first decade. </p>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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Burd, C. G., Swanson, M. S., Gorlach, M., Dreyfuss, G.
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<strong>Primary structures of the heterogeneous nuclear ribonucleoprotein A2, B1, and C2 proteins: a diversity of RNA binding proteins is generated by small peptide inserts.</strong>
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David, C. J., Chen, M., Assanah, M., Canoll, P., Manley, J. L.
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Hamilton, B. J., Nichols, R. C., Tsukamoto, H., Boado, R. J., Pardridge, W. M., Rigby, W. F. C.
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<strong>hnRNP A2 and hnRNP L bind the 3-prime UTR of glucose transporter 1 mRNA and exist as a complex in vivo.</strong>
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Iwanaga, K., Sueoka, N., Sato, A., Hayashi, S., Sueoka, E.
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<strong>Heterogeneous nuclear ribonucleoprotein B1 protein impairs DNA repair mediated through the inhibition of DNA-dependent protein kinase activity.</strong>
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<p class="mim-text-font">
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Kim, H. J., Kim, N. C., Wang, Y.-D., Scarborough, E. A., Moore, J., Diaz, Z., MacLea, K. S., Freibaum, B., Li, S., Molliex, A., and 25 others.
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<strong>Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS.</strong>
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Nature 495: 467-473, 2013.
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[PubMed: 23455423]
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[Full Text: https://doi.org/10.1038/nature11922]
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Kim, H. J., Mohassel, P., Donkervoort, S., Guo, L., O'Donovan, K., Coughlin, M., Lornage, X., Foulds, N., Hammans, S. R., Foley, A. R., Fare, C. M., Ford, A. F., and 46 others.
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<strong>Heterozygous frameshift variants in HNRNPA2B1 cause early-onset oculopharyngeal muscular dystrophy.</strong>
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Nature Commun. 13: 2306, 2022.
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[PubMed: 35484142]
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[Full Text: https://doi.org/10.1038/s41467-022-30015-1]
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Kosturko, L. D., Maggipinto, M. J., Korza, G., Lee, J. W., Carson, J. H., Barbarese, E.
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<strong>Heterogeneous nuclear ribonucleoprotein (hnRNP) E1 binds to hnRNP A2 and inhibits translation of A2 response element mRNAs.</strong>
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Molec. Biol. Cell 17: 3521-3533, 2006.
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Kozu, T., Henrich, B., Schafer, K. P.
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<strong>Structure and expression of the gene (HNRPA2B1) encoding the human hnRNP protein A2/B1.</strong>
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Genomics 25: 365-371, 1995.
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[Full Text: https://doi.org/10.1016/0888-7543(95)80035-k]
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Le Ber, I., Van Bortel, I., Nicolas, G., Bouya-Ahmed, K., Camuzat, A., Wallon, D., De Septenville, A., Latouche, M., Lattante, S., Kabashi, E., Jornea, L., Hannequin, D., Brice, A., French research Network on FTLD/FTLD-ALS.
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<strong>hnRNPA2B1 and hnRNPA1 mutations are rare in patients with 'multisystem proteinopathy' and frontotemporal lobar degeneration phenotypes.</strong>
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Neurobiol. Aging 35: 934.e5-6, 2014.
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[PubMed: 24119545]
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[Full Text: https://doi.org/10.1016/j.neurobiolaging.2013.09.016]
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<p class="mim-text-font">
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Moran-Jones, K., Grindlay, J., Jones, M., Smith, R., Norman, J. C.
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<strong>hnRNP A2 regulates alternative mRNA splicing of TP53INP2 to control invasive cell migration.</strong>
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Cancer Res. 69: 9219-9227, 2009.
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[PubMed: 19934309]
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[Full Text: https://doi.org/10.1158/0008-5472.CAN-09-1852]
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Moran-Jones, K., Wayman, L., Kennedy, D. D., Reddel, R. R., Sara, S., Snee, M. J., Smith, R.
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<strong>hnRNP A2, a potential ssDNA/RNA molecular adapter at the telomere.</strong>
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Nucleic Acids Res. 33: 486-496, 2005.
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[PubMed: 15659580]
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Seelen, M., Visser, A. E., Overste, D. J., Kim, H. J., Palud, A., Wong, T. H., van Swieten, J. C., Scheltens, P., Voermans, N. C., Baas, F., de Jong, J. M. B. V., van der Kooi, A. J., de Visser, M., Veldink, J. H., Taylor, J. P., Van Es, M. A., van den Berg, L. H.
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<strong>No mutations in hnRNPA1 and hnRNPA2B1 in Dutch patients with amyotrophic lateral sclerosis, frontotemporal dementia, and inclusion body myopathy.</strong>
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Neurobiol. Aging 35: 1956.e9-1956.e11, 2014.
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[PubMed: 24612671]
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[Full Text: https://doi.org/10.1016/j.neurobiolaging.2014.01.152]
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Sofola, O. A., Jin, P., Qin, Y., Duan, R., Liu, H., de Haro, M., Nelson, D. L., Botas, J.
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<strong>RNA-binding proteins hnRNP A2/B1 and CUGBP1 suppress fragile X CGG premutation repeat-induced neurodegeneration in a Drosophila model of FXTAS.</strong>
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Neuron 55: 565-571, 2007.
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Waggoner, B., Kovach, M. J., Winkelman, M., Cai, D., Khardori, R., Gelber, D., Kimonis, V. E.
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<strong>Heterogeneity in familial dominant Paget disease of bone and muscular dystrophy.</strong>
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<p class="mim-text-font">
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Wang, L., Wen, M., Cao, X.
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<strong>Nuclear hnRNPA2B1 initiates and amplifies the innate immune response to DNA viruses.</strong>
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Science 365: eaav0758, 2019. Note: Electronic Article.
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[PubMed: 31320558]
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Cassandra L. Kniffin - updated : 08/02/2023<br>Ada Hamosh - updated : 12/20/2019<br>Patricia A. Hartz - updated : 06/22/2017<br>Cassandra L. Kniffin - updated : 7/29/2015<br>Ada Hamosh - updated : 9/24/2013<br>Ada Hamosh - updated : 2/18/2010<br>Patricia A. Hartz - updated : 9/10/2009<br>Alan F. Scott - edited : 12/9/1996
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Victor A. McKusick : 9/22/1994
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carol : 08/07/2023<br>alopez : 08/03/2023<br>ckniffin : 08/02/2023<br>alopez : 12/20/2019<br>mgross : 06/22/2017<br>carol : 07/30/2015<br>mcolton : 7/29/2015<br>ckniffin : 7/29/2015<br>alopez : 3/30/2015<br>alopez : 1/15/2014<br>alopez : 10/18/2013<br>alopez : 9/24/2013<br>alopez : 2/24/2010<br>terry : 2/18/2010<br>mgross : 9/17/2009<br>mgross : 9/17/2009<br>terry : 9/10/2009<br>wwang : 8/27/2008<br>alopez : 6/10/2005<br>alopez : 6/13/1997<br>mark : 12/9/1996<br>mark : 12/9/1996<br>mark : 2/2/1996<br>mark : 5/19/1995<br>carol : 10/13/1994<br>carol : 9/22/1994
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<button type="button" id="mimDonationPopupDonate" class="btn btn-success btn-block" data-dismiss="modal"> Donate To OMIM! </button>
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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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</body>
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</html>
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