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Entry
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- *616381 - ZINC FINGER CCHC DOMAIN-CONTAINING PROTEIN 8; ZCCHC8
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*616381</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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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/616381">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div class="panel 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=ENSG00000033030;t=ENST00000633063" 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=55596" 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=616381" 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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</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=ENSG00000033030;t=ENST00000633063" 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_001350935,NM_001350936,NM_001350937,NM_001350938,NM_017612,XM_047429117,XM_047429118" 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_017612" 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=616381" 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://www.proteinatlas.org/search/ZCCHC8" 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/7018505,14042579,21439026,22760209,34190917,38044290,41946896,66774213,119618731,119618732,158255784,1186518008,1186518010,1186518012,1186518014,2217289869,2217289871,2462532882,2462532884" 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/Q6NZY4" 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=55596" 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=ENSG00000033030;t=ENST00000633063" 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=ZCCHC8" 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=ZCCHC8" 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+55596" 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/ZCCHC8" 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:55596" 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/55596" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr12&hgg_gene=ENST00000633063.3&hgg_start=122471600&hgg_end=122500932&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 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:25265" 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=616381[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=616381[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/ENSG00000033030" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=ZCCHC8" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=ZCCHC8" 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=ZCCHC8" 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=ZCCHC8&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/PA134889410" 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:25265" 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/FBgn0035021.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:1917900" 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/ZCCHC8#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:1917900" 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/55596/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=55596" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="mim#WormbaseGeneFold" id="mimWormbaseGeneToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes."><span id="mimWormbaseGeneToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Wormbase Gene</div>
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<div id="mimWormbaseGeneFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00014018;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00014018 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00021332;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00021332 </a></div>
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</div>
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<div><a href="https://zfin.org/ZDB-GENE-060526-6" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://reactome.org/content/query?q=ZCCHC8&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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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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616381
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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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ZINC FINGER CCHC DOMAIN-CONTAINING PROTEIN 8; ZCCHC8
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=ZCCHC8" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">ZCCHC8</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/12/909?start=-3&limit=10&highlight=909">12q24.31</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr12:122471600-122500932&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">12:122,471,600-122,500,932</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="geneMap" class="mim-anchor"></a>
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<div style="margin-bottom: 10px;">
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<span class="h4 mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
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<a href="/geneMap/12/909?start=-3&limit=10&highlight=909">
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12q24.31
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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?Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 5
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<span class="mim-tip-hint" title="A question mark (?) indicates that the relationship between the phenotype and gene is provisional">
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<span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span>
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</span>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/618674"> 618674 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
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PheneGene Graphics <span class="caret"></span>
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</button>
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<ul class="dropdown-menu" style="width: 17em;">
|
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<li><a href="/graph/linear/616381" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/616381" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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</ul>
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</div>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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</span>
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</span>
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</h4>
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<div>
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<a id="description" class="mim-anchor"></a>
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<div id="mimDescriptionFold" class="collapse in ">
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<span class="mim-text-font">
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<p>ZCCHC8 is a nuclear protein that may play a role in RNA metabolism (<a href="#2" class="mim-tip-reference" title="Gustafson, M. P., Welcker, M., Hwang, H. C., Clurman, B. E. <strong>Zcchc8 is a glycogen synthase kinase-3 substrate that interacts with RNA-binding proteins.</strong> Biochem. Biophys. Res. Commun. 338: 1359-1367, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16263084/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16263084</a>] [<a href="https://doi.org/10.1016/j.bbrc.2005.10.090" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16263084">Gustafson et al., 2005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16263084" 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 SDS-PAGE and mass spectrometry of HeLa cell proteins, <a href="#2" class="mim-tip-reference" title="Gustafson, M. P., Welcker, M., Hwang, H. C., Clurman, B. E. <strong>Zcchc8 is a glycogen synthase kinase-3 substrate that interacts with RNA-binding proteins.</strong> Biochem. Biophys. Res. Commun. 338: 1359-1367, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16263084/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16263084</a>] [<a href="https://doi.org/10.1016/j.bbrc.2005.10.090" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16263084">Gustafson et al. (2005)</a> identified ZCCHC8, which cross-reacted with an antibody directed to a GSK3 (see <a href="/entry/606784">606784</a>) phosphorylation site in MYC (<a href="/entry/190080">190080</a>). The CCHC domain of ZCCHC8 is mainly found in nucleic acid-binding proteins. In human cell lines, ZCCHC8 localized to the nucleus, but it was excluded from the nucleolus. It had an apparent molecular mass of 105 kD by SDS-PAGE. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16263084" 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="#2" class="mim-tip-reference" title="Gustafson, M. P., Welcker, M., Hwang, H. C., Clurman, B. E. <strong>Zcchc8 is a glycogen synthase kinase-3 substrate that interacts with RNA-binding proteins.</strong> Biochem. Biophys. Res. Commun. 338: 1359-1367, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16263084/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16263084</a>] [<a href="https://doi.org/10.1016/j.bbrc.2005.10.090" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16263084">Gustafson et al. (2005)</a> determined that ZCCHC8 was phosphorylated on thr492 (T492) in human cells and cell lines. Total levels of ZCCHC8 increased slightly as cells entered S phase, but T492 phosphorylation increased only as cells entered mitosis. Inhibition of GSK3 via lithium treatment or cotransfection of the AXIN (AXIN1; <a href="/entry/603816">603816</a>) GSK3 interaction domain greatly reduced ZCCHC8 T492 phosphorylation. Using ZCCHC8 as bait in tandem affinity purification of HeLa cell lysates, followed by SDS-PAGE and mass spectrometric analysis, <a href="#2" class="mim-tip-reference" title="Gustafson, M. P., Welcker, M., Hwang, H. C., Clurman, B. E. <strong>Zcchc8 is a glycogen synthase kinase-3 substrate that interacts with RNA-binding proteins.</strong> Biochem. Biophys. Res. Commun. 338: 1359-1367, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16263084/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16263084</a>] [<a href="https://doi.org/10.1016/j.bbrc.2005.10.090" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16263084">Gustafson et al. (2005)</a> found that ZCCHC8 interacted with the RNA-splicing factor RBM7 (<a href="/entry/612413">612413</a>) and with the DExH box RNA helicase SKIV2L2. Cotransfection of HeLa cells confirmed that ZCCHC8 interacted with epitope-tagged RBM7 and SKIV2L2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16263084" 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="Gable, D. L., Gaysinskaya, V., Atik, C. C. Talbot, C. C., Jr., Kang, B., Stanley, S. E., Pugh, E. W., Amat-Codina, N., Schenk, K. M., Arcasoy, M. O., Brayton, C., Florea, L., Armanios, M. <strong>ZCCHC8, the nuclear exosome targeting component, is mutated in familial pulmonary fibrosis and is required for telomerase RNA maturation.</strong> Genes Dev. 33: 1381-1396, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31488579/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31488579</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31488579[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1101/gad.326785.119" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31488579">Gable et al. (2019)</a> found that knockdown of ZCCHC8 in HeLa cells using shRNA resulted in decreased levels of TERC (<a href="/entry/602322">602322</a>). Additional detailed cellular studies showed that ZCCHC8 is required for TERC maturation and telomerase function, particularly mediating TERC 3-prime end targeting to the nuclear RNA exosome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31488579" 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 3 members of a family with telomere-related pulmonary fibrosis and/or bone marrow failure syndrome-5 (PFBMFT5; <a href="/entry/618674">618674</a>), <a href="#1" class="mim-tip-reference" title="Gable, D. L., Gaysinskaya, V., Atik, C. C. Talbot, C. C., Jr., Kang, B., Stanley, S. E., Pugh, E. W., Amat-Codina, N., Schenk, K. M., Arcasoy, M. O., Brayton, C., Florea, L., Armanios, M. <strong>ZCCHC8, the nuclear exosome targeting component, is mutated in familial pulmonary fibrosis and is required for telomerase RNA maturation.</strong> Genes Dev. 33: 1381-1396, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31488579/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31488579</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31488579[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1101/gad.326785.119" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31488579">Gable et al. (2019)</a> identified a heterozygous missense mutation in the ZCCHC8 gene (P186L; <a href="#0001">616381.0001</a>). The mutation, which was found by a combination of linkage analysis and whole-genome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Two younger asymptomatic family members who had short telomeres also carried the mutation. The mutation was not found in the 1000 Genomes Project, Exome Sequencing Project, ExAC, or gnomAD databases. Analysis of patient cells showed a 50% decrease in ZCCHC8 protein levels compared to controls, suggesting that the mutation compromised protein stability. Patient cells also showed dysregulation of RNA processing, with abnormal accumulation of TERC precursors at the expense of mature TERC. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31488579" 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="Gable, D. L., Gaysinskaya, V., Atik, C. C. Talbot, C. C., Jr., Kang, B., Stanley, S. E., Pugh, E. W., Amat-Codina, N., Schenk, K. M., Arcasoy, M. O., Brayton, C., Florea, L., Armanios, M. <strong>ZCCHC8, the nuclear exosome targeting component, is mutated in familial pulmonary fibrosis and is required for telomerase RNA maturation.</strong> Genes Dev. 33: 1381-1396, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31488579/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31488579</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31488579[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1101/gad.326785.119" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31488579">Gable et al. (2019)</a> found that homozygous loss of Zcchc8 in mice resulted in postnatal lethality by 70 days. Zcchc8-null mice showed progressive neurodevelopmental defects, with small brain volume, defective neurogenesis, and hydrocephalus. Some of the features were consistent with a ciliopathy. These abnormalities were associated with defective turnover of low abundance RNA polymerase II (see <a href="/entry/180660">180660</a>) transcripts and abnormal accumulation of other low abundance RNAs, including histones and RNAs that encode cilia protein components. The findings were consistent with dysregulation of RNA processing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31488579" 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>.0001 PULMONARY FIBROSIS AND/OR BONE MARROW FAILURE SYNDROME, TELOMERE-RELATED, 5 (1 family)</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs1317757765 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1317757765;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs1317757765?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1317757765" 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=rs1317757765" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 3 members of a family with telomere-related pulmonary fibrosis and/or bone marrow failure syndrome-5 (PFBMFT5; <a href="/entry/618674">618674</a>), <a href="#1" class="mim-tip-reference" title="Gable, D. L., Gaysinskaya, V., Atik, C. C. Talbot, C. C., Jr., Kang, B., Stanley, S. E., Pugh, E. W., Amat-Codina, N., Schenk, K. M., Arcasoy, M. O., Brayton, C., Florea, L., Armanios, M. <strong>ZCCHC8, the nuclear exosome targeting component, is mutated in familial pulmonary fibrosis and is required for telomerase RNA maturation.</strong> Genes Dev. 33: 1381-1396, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31488579/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31488579</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31488579[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1101/gad.326785.119" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31488579">Gable et al. (2019)</a> identified a heterozygous c.557C-T transition in the ZCCHC8 gene, resulting in a pro186-to-leu (P186L) substitution at a highly conserved residue. The mutation, which was found by a combination of linkage analysis and whole-genome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Two younger asymptomatic family members who had short telomeres also carried the mutation. The mutation was not found in the 1000 Genomes Project, Exome Sequencing Project, ExAC, or gnomAD databases. Analysis of patient cells showed a 50% decrease in ZCCHC8 protein levels compared to controls, suggesting that the mutation compromised protein stability. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31488579" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="Gable2019" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Gable, D. L., Gaysinskaya, V., Atik, C. C. Talbot, C. C., Jr., Kang, B., Stanley, S. E., Pugh, E. W., Amat-Codina, N., Schenk, K. M., Arcasoy, M. O., Brayton, C., Florea, L., Armanios, M.
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<strong>ZCCHC8, the nuclear exosome targeting component, is mutated in familial pulmonary fibrosis and is required for telomerase RNA maturation.</strong>
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Genes Dev. 33: 1381-1396, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31488579/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31488579</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31488579[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=31488579" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1101/gad.326785.119" target="_blank">Full Text</a>]
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<li>
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<a id="2" class="mim-anchor"></a>
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<a id="Gustafson2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Gustafson, M. P., Welcker, M., Hwang, H. C., Clurman, B. E.
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<strong>Zcchc8 is a glycogen synthase kinase-3 substrate that interacts with RNA-binding proteins.</strong>
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Biochem. Biophys. Res. Commun. 338: 1359-1367, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16263084/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16263084</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16263084" 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.bbrc.2005.10.090" target="_blank">Full Text</a>]
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<a id="Hartz2015" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Hartz, P. A.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 5/21/2015.
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<span class="mim-text-font">
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Contributors:
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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 : 11/27/2019
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<span class="text-nowrap mim-text-font">
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Creation Date:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Patricia A. Hartz : 5/21/2015
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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alopez : 05/08/2023
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<span class="mim-text-font">
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alopez : 11/27/2019<br>ckniffin : 11/27/2019<br>mgross : 05/26/2015<br>mcolton : 5/21/2015
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<span class="mim-font">
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<strong>*</strong> 616381
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<h3>
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ZINC FINGER CCHC DOMAIN-CONTAINING PROTEIN 8; ZCCHC8
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: ZCCHC8</em></strong>
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<strong>
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<em>
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Cytogenetic location: 12q24.31
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Genomic coordinates <span class="small">(GRCh38)</span> : 12:122,471,600-122,500,932 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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<strong>Gene-Phenotype Relationships</strong>
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<table class="table table-bordered table-condensed small mim-table-padding">
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Location
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Phenotype
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</th>
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Phenotype <br /> MIM number
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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<span class="mim-font">
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12q24.31
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<span class="mim-font">
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?Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 5
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<span class="mim-font">
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618674
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant
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</td>
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<td>
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<span class="mim-font">
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3
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<strong>TEXT</strong>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</div>
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<span class="mim-text-font">
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<p>ZCCHC8 is a nuclear protein that may play a role in RNA metabolism (Gustafson et al., 2005). </p>
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</span>
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<div>
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<br />
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</div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>By SDS-PAGE and mass spectrometry of HeLa cell proteins, Gustafson et al. (2005) identified ZCCHC8, which cross-reacted with an antibody directed to a GSK3 (see 606784) phosphorylation site in MYC (190080). The CCHC domain of ZCCHC8 is mainly found in nucleic acid-binding proteins. In human cell lines, ZCCHC8 localized to the nucleus, but it was excluded from the nucleolus. It had an apparent molecular mass of 105 kD by SDS-PAGE. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Gustafson et al. (2005) determined that ZCCHC8 was phosphorylated on thr492 (T492) in human cells and cell lines. Total levels of ZCCHC8 increased slightly as cells entered S phase, but T492 phosphorylation increased only as cells entered mitosis. Inhibition of GSK3 via lithium treatment or cotransfection of the AXIN (AXIN1; 603816) GSK3 interaction domain greatly reduced ZCCHC8 T492 phosphorylation. Using ZCCHC8 as bait in tandem affinity purification of HeLa cell lysates, followed by SDS-PAGE and mass spectrometric analysis, Gustafson et al. (2005) found that ZCCHC8 interacted with the RNA-splicing factor RBM7 (612413) and with the DExH box RNA helicase SKIV2L2. Cotransfection of HeLa cells confirmed that ZCCHC8 interacted with epitope-tagged RBM7 and SKIV2L2. </p><p>Gable et al. (2019) found that knockdown of ZCCHC8 in HeLa cells using shRNA resulted in decreased levels of TERC (602322). Additional detailed cellular studies showed that ZCCHC8 is required for TERC maturation and telomerase function, particularly mediating TERC 3-prime end targeting to the nuclear RNA exosome. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Hartz (2015) mapped the ZCCHC8 gene to chromosome 12q24.31 based on an alignment of the ZCCHC8 sequence (GenBank BC017704) with the genomic sequence (GRCh38).</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In 3 members of a family with telomere-related pulmonary fibrosis and/or bone marrow failure syndrome-5 (PFBMFT5; 618674), Gable et al. (2019) identified a heterozygous missense mutation in the ZCCHC8 gene (P186L; 616381.0001). The mutation, which was found by a combination of linkage analysis and whole-genome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Two younger asymptomatic family members who had short telomeres also carried the mutation. The mutation was not found in the 1000 Genomes Project, Exome Sequencing Project, ExAC, or gnomAD databases. Analysis of patient cells showed a 50% decrease in ZCCHC8 protein levels compared to controls, suggesting that the mutation compromised protein stability. Patient cells also showed dysregulation of RNA processing, with abnormal accumulation of TERC precursors at the expense of mature TERC. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Gable et al. (2019) found that homozygous loss of Zcchc8 in mice resulted in postnatal lethality by 70 days. Zcchc8-null mice showed progressive neurodevelopmental defects, with small brain volume, defective neurogenesis, and hydrocephalus. Some of the features were consistent with a ciliopathy. These abnormalities were associated with defective turnover of low abundance RNA polymerase II (see 180660) transcripts and abnormal accumulation of other low abundance RNAs, including histones and RNAs that encode cilia protein components. The findings were consistent with dysregulation of RNA processing. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>1 Selected Example):</strong>
|
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</span>
|
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</h4>
|
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0001 PULMONARY FIBROSIS AND/OR BONE MARROW FAILURE SYNDROME, TELOMERE-RELATED, 5 (1 family)</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ZCCHC8, PRO186LEU
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<br />
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SNP: rs1317757765,
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gnomAD: rs1317757765,
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|
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ClinVar: RCV000856725, RCV004546569
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 3 members of a family with telomere-related pulmonary fibrosis and/or bone marrow failure syndrome-5 (PFBMFT5; 618674), Gable et al. (2019) identified a heterozygous c.557C-T transition in the ZCCHC8 gene, resulting in a pro186-to-leu (P186L) substitution at a highly conserved residue. The mutation, which was found by a combination of linkage analysis and whole-genome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Two younger asymptomatic family members who had short telomeres also carried the mutation. The mutation was not found in the 1000 Genomes Project, Exome Sequencing Project, ExAC, or gnomAD databases. Analysis of patient cells showed a 50% decrease in ZCCHC8 protein levels compared to controls, suggesting that the mutation compromised protein stability. </p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
|
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
|
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Gable, D. L., Gaysinskaya, V., Atik, C. C. Talbot, C. C., Jr., Kang, B., Stanley, S. E., Pugh, E. W., Amat-Codina, N., Schenk, K. M., Arcasoy, M. O., Brayton, C., Florea, L., Armanios, M.
|
|
<strong>ZCCHC8, the nuclear exosome targeting component, is mutated in familial pulmonary fibrosis and is required for telomerase RNA maturation.</strong>
|
|
Genes Dev. 33: 1381-1396, 2019.
|
|
|
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|
|
[PubMed: 31488579]
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|
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[Full Text: https://doi.org/10.1101/gad.326785.119]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Gustafson, M. P., Welcker, M., Hwang, H. C., Clurman, B. E.
|
|
<strong>Zcchc8 is a glycogen synthase kinase-3 substrate that interacts with RNA-binding proteins.</strong>
|
|
Biochem. Biophys. Res. Commun. 338: 1359-1367, 2005.
|
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[PubMed: 16263084]
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[Full Text: https://doi.org/10.1016/j.bbrc.2005.10.090]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Hartz, P. A.
|
|
<strong>Personal Communication.</strong>
|
|
Baltimore, Md. 5/21/2015.
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</p>
|
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</li>
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</ol>
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<div>
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Cassandra L. Kniffin - updated : 11/27/2019
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Patricia A. Hartz : 5/21/2015
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alopez : 05/08/2023<br>alopez : 11/27/2019<br>ckniffin : 11/27/2019<br>mgross : 05/26/2015<br>mcolton : 5/21/2015
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