3235 lines
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Entry
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- *607640 - ATAXIN 7; ATXN7
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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">*607640</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="#geneStructure">Gene Structure</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="#geneFunction">Gene Function</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/607640">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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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=ENSG00000163635;t=ENST00000674280" 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=6314" 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=607640" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</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=ENSG00000163635;t=ENST00000674280" 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_000333,NM_001128149,NM_001177387,NM_001377405,NM_001377406,NR_165269,NR_165270" 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_001377405" 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=607640" 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=06365&isoform_id=06365_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/ATXN7" 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/2370155,2655041,3192948,3192950,3192952,3192954,4506797,5921169,18874079,119585826,119585827,194384392,293651611,293651613,1792641352,1792650180" 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/O15265" 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=6314" 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=ENSG00000163635;t=ENST00000674280" 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=ATXN7" 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=ATXN7" 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+6314" 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/ATXN7" 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:6314" 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/6314" 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=chr3&hgg_gene=ENST00000674280.1&hgg_start=63863144&hgg_end=64003462&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://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=607640[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 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=607640[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/ENSG00000163635" 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=ATXN7" 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=ATXN7" 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=ATXN7" 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=ATXN7&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/PA34973" 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:10560" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:2179277" 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/ATXN7#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:2179277" 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/6314/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=6314" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-110621-1" 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=ATXN7&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 715726000<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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607640
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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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ATAXIN 7; ATXN7
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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=ATXN7" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">ATXN7</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/3/436?start=-3&limit=10&highlight=436">3p14.1</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr3:63863144-64003462&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'})">3:63,863,144-64,003,462</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/3/436?start=-3&limit=10&highlight=436">
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3p14.1
|
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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Spinocerebellar ataxia 7
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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/164500"> 164500 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/607640" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/607640" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<div>
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<p />
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
|
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<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>ATXN7 is a transcription factor that appears to be critically important for chromatin remodeling at the level of histone acetylation and deubiquitination. It is a core component of 2 different transcription coactivator complexes: the SPT3 (SUPT3H; <a href="/entry/602947">602947</a>)/TAF9 (<a href="/entry/600822">600822</a>)/GCN5 (KAT2A; <a href="/entry/602301">602301</a>) acetyltransferase (STAGA) complex, which has histone acetyltransferase activity, and the USP22 (<a href="/entry/612116">612116</a>) deubiquitination complex (summary by <a href="#18" class="mim-tip-reference" title="Sopher, B. L., Ladd, P. D., Pineda, V. V., Libby, R. T., Sunkin, S. M., Hurley, J. B., Thienes, C. P., Gaasterland, T., Filippova, G. N., La Spada, A. R. <strong>CTCF regulates ataxin-7 expression through promotion of a convergently transcribed, antisense noncoding RNA.</strong> Neuron 70: 1071-1084, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21689595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21689595</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21689595[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.2011.05.027" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21689595">Sopher et al., 2011</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21689595" 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 positional cloning, <a href="#3" class="mim-tip-reference" title="David, G., Abbas, N., Stevanin, G., Durr, A., Yvert, G., Cancel, G., Weber, C., Imbert, G., Saudou, F., Antoniou, E., Drabkin, H., Gemmill, R., Giunti, P., Benomar, A., Wood, N., Ruberg, M., Agid, Y., Mandel, J.-L., Brice, A. <strong>Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansion.</strong> Nature Genet. 17: 65-70, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9288099/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9288099</a>] [<a href="https://doi.org/10.1038/ng0997-65" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9288099">David et al. (1997)</a> identified the causative gene for spinocerebellar ataxia-7 (<a href="/entry/164500">164500</a>). The ATXN7 gene has a 2,727-bp open reading frame predicting an 892-amino acid polypeptide, designated ataxin-7, with a nuclear localization signal and a polyglutamine (polyQ) tract. In the consensus cDNA sequence, a 9-residue polyglutamine tract is encoded by CAG repeats at codons 30 to 39. Mutated disease alleles have expanded repeats (see MOLECULAR GENETICS). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9288099" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Einum, D. D., Clark, A. M., Townsend, J. J., Ptacek, L. J., Fu, Y.-H. <strong>A novel central nervous system-enriched spinocerebellar ataxia type 7 gene product.</strong> Arch. Neurol. 60: 97-103, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12533095/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12533095</a>] [<a href="https://doi.org/10.1001/archneur.60.1.97" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12533095">Einum et al. (2003)</a> identified an ATXN7 splice variant, termed ataxin-7b, which contains an additional 67 basepairs between exons 12 and 13, and predicts a 945-amino acid protein with a molecular mass of 101 kD. Northern blot analysis revealed a 4.5-kb transcript expressed predominantly throughout the CNS. Immunohistochemistry revealed intense cytoplasmic staining in cerebellar Purkinje cells, inferior olivary neurons, and retinal photoreceptor cells. <a href="#4" class="mim-tip-reference" title="Einum, D. D., Clark, A. M., Townsend, J. J., Ptacek, L. J., Fu, Y.-H. <strong>A novel central nervous system-enriched spinocerebellar ataxia type 7 gene product.</strong> Arch. Neurol. 60: 97-103, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12533095/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12533095</a>] [<a href="https://doi.org/10.1001/archneur.60.1.97" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12533095">Einum et al. (2003)</a> suggested that expanded polyglutamine repeats in ataxin-7b also contribute to neurodegeneration and that expression of multiple polyglutamine-containing proteins may result in selective patterns of neurodegeneration. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12533095" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Sopher, B. L., Ladd, P. D., Pineda, V. V., Libby, R. T., Sunkin, S. M., Hurley, J. B., Thienes, C. P., Gaasterland, T., Filippova, G. N., La Spada, A. R. <strong>CTCF regulates ataxin-7 expression through promotion of a convergently transcribed, antisense noncoding RNA.</strong> Neuron 70: 1071-1084, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21689595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21689595</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21689595[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.2011.05.027" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21689595">Sopher et al. (2011)</a> identified human ATXN7 variants that initiate from an alternative promoter (P2A) and transcription start site in the 3-prime end of intron 2. These variants differ from previously reported ATXN7 transcripts in their 5-prime UTR, but the translational start site is unchanged. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21689595" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#19" class="mim-tip-reference" title="Strom, A.-L., Jonasson, J., Hart, P., Brannstrom, T., Forsgren, L., Holmberg, M. <strong>Cloning and expression analysis of the murine homolog of the spinocerebellar ataxia type 7 (SCA7) gene.</strong> Gene 285: 91-99, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12039035/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12039035</a>] [<a href="https://doi.org/10.1016/s0378-1119(02)00399-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12039035">Strom et al. (2002)</a> cloned the mouse Sca7 cDNA from a brain cDNA library. The deduced 867-amino acid protein shows 88.7% identity with the human protein. The mouse CAG region contained only 5 repeats in 3 different strains examined. Northern blot analysis detected expression of Sca7 in all adult mouse tissues, with highest expression in heart, brain, liver, and kidney. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12039035" 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="#15" class="mim-tip-reference" title="Michalik, A., Del-Favero, J., Mauger, C., Lofgren, A., Van Broeckhoven, C. <strong>Genomic organisation of the spinocerebellar ataxia type 7 (SCA7) gene responsible for autosomal dominant cerebellar ataxia with retinal degeneration.</strong> Hum. Genet. 105: 410-417, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10598805/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10598805</a>] [<a href="https://doi.org/10.1007/s004390051123" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10598805">Michalik et al. (1999)</a> reported that the ATXN7 gene contains 13 exons that range in size from 69 to 979 bp. The ATG initiation codon at position 554 of the cDNA occurs in exon 3 at position 12, and the coding region extends to the first 5 codons of exon 13. The CAG repeat is located in exon 3, starting at codon 30. The introns vary in size from 233 bp to about 40 kb, resulting in an overall size for the ATXN7 gene of about 140 kb. Sequence analysis of intron 7 (491 bp) revealed a polymorphic GT/AC repeat, a useful intragenic marker for ATXN7 in segregation studies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10598805" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Sopher, B. L., Ladd, P. D., Pineda, V. V., Libby, R. T., Sunkin, S. M., Hurley, J. B., Thienes, C. P., Gaasterland, T., Filippova, G. N., La Spada, A. R. <strong>CTCF regulates ataxin-7 expression through promotion of a convergently transcribed, antisense noncoding RNA.</strong> Neuron 70: 1071-1084, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21689595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21689595</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21689595[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.2011.05.027" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21689595">Sopher et al. (2011)</a> identified an alternative promoter (P2A) in ATXN7 that initiates transcription at an alternate start site in the 3-prime end of intron 2. Variants initiated from P2A contain a single first exon comprising the last 400 bp of intron 2 and exon 3, or instead have a shorter exon (2A) spliced to exon 3. The translational start site is unchanged. Binding sites for the transcriptional regulator CTCF (<a href="/entry/604167">604167</a>) flank exon 3. Mice have a single Atxn7 promoter corresponding to human P2A. <a href="#18" class="mim-tip-reference" title="Sopher, B. L., Ladd, P. D., Pineda, V. V., Libby, R. T., Sunkin, S. M., Hurley, J. B., Thienes, C. P., Gaasterland, T., Filippova, G. N., La Spada, A. R. <strong>CTCF regulates ataxin-7 expression through promotion of a convergently transcribed, antisense noncoding RNA.</strong> Neuron 70: 1071-1084, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21689595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21689595</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21689595[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.2011.05.027" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21689595">Sopher et al. (2011)</a> also identified identified SCAANT1 (ATXN7AS1; <a href="/entry/614481">614481</a>), an ATXN7 antisense transcript on the opposite strand. SCAANT1 transcription begins in ATXN7 intron 4 and covers exon 4, exon 3, including the translational start site and the CAG repeat region, and the P2A promoter of ATXN7. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21689595" 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="#6" class="mim-tip-reference" title="Gross, M. B. <strong>Personal Communication.</strong> Baltimore, Md. 2/14/2012."None>Gross (2012)</a> mapped the ATXN7 gene to chromosome 3p14.1 based on an alignment of the ATXN7 sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=AF032105" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">AF032105</a>) with the genomic sequence (GRCh37).</p>
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<p><a href="#10" class="mim-tip-reference" title="Kaytor, M. D., Duvick, L. A., Skinner, P. J., Koob, M. D., Ranum, L. P. W., Orr, H. T. <strong>Nuclear localization of the spinocerebellar ataxia type 7 protein, ataxin-7.</strong> Hum. Molec. Genet. 8: 1657-1664, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10441328/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10441328</a>] [<a href="https://doi.org/10.1093/hmg/8.9.1657" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10441328">Kaytor et al. (1999)</a> examined the subcellular localization of ataxin-7 in transfected COS-1 cells, using ATXN7 cDNA clones with different CAG repeat tract lengths. In addition to a diffuse distribution throughout the nucleus, ataxin-7 associated with the nuclear matrix and the nucleolus. The location of the putative ATXN7 nuclear localization sequence (NLS) was confirmed by fusing an ataxin-7 fragment with chicken muscle pyruvate kinase, a normally cytoplasmic protein. Mutation of this NLS prevented protein from entering the nucleus. Thus, expanded ataxin-7 may carry out its pathogenic effects in the nucleus by altering a matrix-associated nuclear structure and/or by disrupting nucleolar function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10441328" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Lebre, A.-S., Jamot, L., Takahashi, J., Spassky, N., Leprince, C., Ravise, N., Zander, C., Fujigasaki, H., Kussel-Andermann, P., Duyckaerts, C., Camonis, J. H., Brice, A. <strong>Ataxin-7 interacts with a Cbl-associated protein that it recruits into neuronal intranuclear inclusions.</strong> Hum. Molec. Genet. 10: 1201-1213, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11371513/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11371513</a>] [<a href="https://doi.org/10.1093/hmg/10.11.1201" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11371513">Lebre et al. (2001)</a> used a 2-hybrid approach to screen a human retina cDNA library for ataxin-7-binding proteins and isolated R85, a splice variant of Cbl-associated protein (CAP; <a href="/entry/605264">605264</a>). R85 and CAP are generated by alternative splicing of the SH3P12 gene, which was localized on chromosome 10q23-q24. The interaction between ataxin-7 and the SH3P12 gene products was confirmed by pull-down and coimmunoprecipitation. SH3P12 gene products are expressed in Purkinje cells in the cerebellum. Ataxin-7 colocalizes with full-length R85 in cotransfected COS-7 cells and with one of the SH3P12 gene products in neuronal intranuclear inclusions in brain from a SCA7 patient. The authors proposed that this interaction may be part of a physiologic pathway related to the function or turnover of ataxin-7. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11371513" 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>To analyze the effects of overexpression of mutant ataxin-7 protein, <a href="#22" class="mim-tip-reference" title="Zander, C., Takahashi, J., El Hachimi, K. H., Fujigasaki, H., Albanese, V., Lebre, A. S., Stevanin, G., Duyckaerts, C., Brice, A. <strong>Similarities between spinocerebellar ataxia type 7 (SCA7) cell models and human brain: proteins recruited in inclusions and activation of caspase-3.</strong> Hum. Molec. Genet. 10: 2569-2579, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11709544/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11709544</a>] [<a href="https://doi.org/10.1093/hmg/10.22.2569" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11709544">Zander et al. (2001)</a> established ATXN7 cell culture models in kidney and neuroblastoma cell lines. The cells readily formed anti-ataxin-7-positive fibrillar inclusions and small, nuclear electron-dense structures. Comparable to the inclusions in human SCA7 brain tissue, there were consistent signs of ongoing abnormal protein folding, including the recruitment of heat-shock proteins and proteasome subunits. Occasionally, sequestered transcription factors were found. Activated caspase-3 (<a href="/entry/600636">600636</a>) was recruited into the inclusions in both the cell models and human SCA7 brain, and its expression was upregulated in cortical neurons, suggesting that it may play a role in the disease process. On the ultrastructural level, there were signs of autophagy and nuclear indentations, indicative of a major stress response in cells expressing mutant ataxin-7. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11709544" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Matilla, A., Gorbea, C., Einum, D. D., Townsend, J., Michalik, A., van Broeckhoven, C., Jensen, C. C., Murphy, K. J., Ptacek, L. J., Fu, Y.-H. <strong>Association of ataxin-7 with the proteasome subunit S4 of the 19S regulatory complex.</strong> Hum. Molec. Genet. 10: 2821-2831, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11734547/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11734547</a>] [<a href="https://doi.org/10.1093/hmg/10.24.2821" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11734547">Matilla et al. (2001)</a> used a 2-hybrid assay to show that ataxin-7 interacts with the ATPase subunit S4 of the 19S regulatory complex of the 26S proteasome (<a href="/entry/602706">602706</a>). The ataxin-7/S4 association was modulated by the length of the polyglutamine tract, whereby S4 showed a stronger association with the wildtype allele of ataxin-7. Endogenous ataxin-7 localized to discrete nuclear foci that also contained additional components of the proteasomal complex. Immunohistochemical analyses suggested alterations either of the distribution or the levels of S4 immunoreactivity in neurons that degenerate in SCA7 brains. Immunoblot analyses demonstrated reduced levels of S4 in SCA7 cerebella without evident alterations in the levels of other proteasome subunits. The authors suggested a role for S4 and ubiquitin-mediated proteasomal proteolysis in the molecular pathogenesis of SCA7. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11734547" 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 combining profile-based sequence analysis with genomewide functional data in model organisms, <a href="#17" class="mim-tip-reference" title="Scheel, H., Tomiuk, S., Hofmann, K. <strong>Elucidation of ataxin-3 and ataxin-7 function by integrative bioinformatics.</strong> Hum. Molec. Genet. 12: 2845-2852, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12944423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12944423</a>] [<a href="https://doi.org/10.1093/hmg/ddg297" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12944423">Scheel et al. (2003)</a> found that ATXN7 is orthologous to the yeast open reading frame Ygl066c. Evidence suggested that Ygl066c is a component of the SAGA histone acetyltransferase complex. <a href="#17" class="mim-tip-reference" title="Scheel, H., Tomiuk, S., Hofmann, K. <strong>Elucidation of ataxin-3 and ataxin-7 function by integrative bioinformatics.</strong> Hum. Molec. Genet. 12: 2845-2852, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12944423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12944423</a>] [<a href="https://doi.org/10.1093/hmg/ddg297" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12944423">Scheel et al. (2003)</a> suggested the finding had implications for disease pathogenesis by providing a direct connection between SCA7 and histone acetylation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12944423" 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 putative ataxin-7 yeast ortholog, SGF73 (Ygl066c), is a component of the SAGA (Spt/Ada/Gcn5 acetylase) multisubunit complex, a coactivator required for transcription of a subset of RNA polymerase II (see <a href="/entry/180660">180660</a>)-dependent genes (<a href="#5" class="mim-tip-reference" title="Gavin, A. C., Bosche, M., Krause, R., Grandi, P., Marzioch, M., Bauer, A., Schultz, J., Rick, J. M., Michon, A. M., Cruciat, C.-M., Remor, M., Hofert, C., and 26 others. <strong>Functional organization of the yeast proteome by systematic analysis of protein complexes.</strong> Nature 415: 141-147, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11805826/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11805826</a>] [<a href="https://doi.org/10.1038/415141a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11805826">Gavin et al., 2002</a>; <a href="#16" class="mim-tip-reference" title="Sanders, S. L., Jennings, J., Canutescu, A., Link, A. J., Weil, P. A. <strong>Proteomics of the eukaryotic transcription machinery: identification of proteins associated with components of yeast TFIID by multidimensional mass spectrometry.</strong> Molec. Cell. Biol. 22: 4723-4738, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12052880/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12052880</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12052880[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/10.1128/MCB.22.13.4723-4738.2002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12052880">Sanders et al., 2002</a>). <a href="#7" class="mim-tip-reference" title="Helmlinger, D., Hardy, S., Sasorith, S., Klein, F., Robert, F., Weber, C., Miguet, L., Potier, N., Van-Dorsselaer, A., Wurtz, J.-M., Mandel, J.-L., Tora, L., Devys, D. <strong>Ataxin-7 is a subunit of GCN5 histone acetyltransferase-containing complexes.</strong> Hum. Molec. Genet. 13: 1257-1265, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15115762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15115762</a>] [<a href="https://doi.org/10.1093/hmg/ddh139" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15115762">Helmlinger et al. (2004)</a> showed that ataxin-7 is an integral component of the mammalian SAGA-like complexes TFTC (TATA-binding protein-free TAF-containing complex) and STAGA (SPT3 (<a href="/entry/602947">602947</a>)/TAF9 (<a href="/entry/600822">600822</a>)/GCN5 (<a href="/entry/602301">602301</a>) acetyltransferase complex). Immunopurified ataxin-7 complex retained histone acetyltransferase (see <a href="/entry/603053">603053</a>) activity, characteristic for TFTC-like complexes. The authors identified a 71-amino acid domain in ataxin-7 that is required for interaction with TFTC/STAGA subunits and is conserved highly through evolution, allowing the identification of a ATXN7 gene family. This domain contains a conserved cys3-his motif that binds zinc, forming a new zinc-binding domain. Polyglutamine expansion in ataxin-7 did not affect its incorporation into TFTC/STAGA complexes purified from SCA7 patient cells. The authors concluded that ataxin-7 is the human ortholog of the yeast SAGA SGF73 subunit and is a bona fide subunit of the human TFTC-like transcriptional complexes. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11805826+12052880+15115762" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In an SCA7 transgenic mouse model, <a href="#11" class="mim-tip-reference" title="La Spada, A. R., Fu, Y.-H., Sopher, B. L., Libby, R. T., Wang, X., Li, L. Y., Einum, D. D., Huang, J., Possin, D. E., Smith, A. C., Martinez, R. A., Koszdin, K. L., Treuting, P. M., Ware, C. B., Hurley, J. B., Ptacek, L. J., Chen, S. <strong>Polyglutamine-expanded ataxin-7 antagonizes CRX function and induces cone-rod dystrophy in a mouse model of SCA7.</strong> Neuron 31: 913-927, 2001. Note: Erratum: Neuron 32: 957-958, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11580893/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11580893</a>] [<a href="https://doi.org/10.1016/s0896-6273(01)00422-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11580893">La Spada et al. (2001)</a> found that the cone-rod dystrophy involved altered photoreceptor gene expression due to interference with CRX (<a href="/entry/602225">602225</a>), a homeodomain transcription factor containing a glutamine-rich region. By coimmunoprecipitation analysis of CRX and ATXN7 truncation and point mutants, <a href="#2" class="mim-tip-reference" title="Chen, S., Peng, G.-H., Wang, X., Smith, A. C., Grote, S. K., Sopher, B. L., La Spada, A. R. <strong>Interference of Crx-dependent transcription by ataxin-7 involves interaction between the glutamine regions and requires the ataxin-7 carboxy-terminal region for nuclear localization.</strong> Hum. Molec. Genet. 13: 53-67, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14613968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14613968</a>] [<a href="https://doi.org/10.1093/hmg/ddh005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14613968">Chen et al. (2004)</a> determined that the ATXN7-interacting domain of CRX localized to its glutamine-rich region and the CRX-interacting domain of ATXN7 localized to its glutamine tract. Nuclear localization of ataxin-7 was required to repress Crx transactivation, and the likely nuclear localization signals were mapped to the C-terminal region of ataxin-7. Using chromatin immunoprecipitation, the authors showed that both Crx and ataxin-7 occupied the promoter and enhancer regions of Crx-regulated retinal genes in vivo. <a href="#2" class="mim-tip-reference" title="Chen, S., Peng, G.-H., Wang, X., Smith, A. C., Grote, S. K., Sopher, B. L., La Spada, A. R. <strong>Interference of Crx-dependent transcription by ataxin-7 involves interaction between the glutamine regions and requires the ataxin-7 carboxy-terminal region for nuclear localization.</strong> Hum. Molec. Genet. 13: 53-67, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14613968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14613968</a>] [<a href="https://doi.org/10.1093/hmg/ddh005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14613968">Chen et al. (2004)</a> suggested that one mechanism of SCA7 disease pathogenesis may be transcription dysregulation, and that CRX transcription interference may be a predominant factor in SCA7 cone-rod dystrophy retinal degeneration. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14613968+11580893" 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>Regulation of ATXN7 by ATXN7AS1</em></strong></p><p>
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By quantitative RT-PCR of human human tissues, <a href="#18" class="mim-tip-reference" title="Sopher, B. L., Ladd, P. D., Pineda, V. V., Libby, R. T., Sunkin, S. M., Hurley, J. B., Thienes, C. P., Gaasterland, T., Filippova, G. N., La Spada, A. R. <strong>CTCF regulates ataxin-7 expression through promotion of a convergently transcribed, antisense noncoding RNA.</strong> Neuron 70: 1071-1084, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21689595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21689595</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21689595[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.2011.05.027" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21689595">Sopher et al. (2011)</a> observed inverse expression of ATXN7 and its antisense transcript, SCAANT1 (ATXN7AS1; <a href="/entry/614481">614481</a>). ATXN7 expression was high in cortex, cerebellum, striatum, and liver and weak in lung and kidney, whereas SCAANT1 expression was weak in brain tissues and liver and high in lung and kidney. Qualitative RT-PCR revealed abnormally elevated ATXN7 expression and reduced SCAANT1 expression in SCA7 patient fibroblasts and peripheral blood samples. <a href="#18" class="mim-tip-reference" title="Sopher, B. L., Ladd, P. D., Pineda, V. V., Libby, R. T., Sunkin, S. M., Hurley, J. B., Thienes, C. P., Gaasterland, T., Filippova, G. N., La Spada, A. R. <strong>CTCF regulates ataxin-7 expression through promotion of a convergently transcribed, antisense noncoding RNA.</strong> Neuron 70: 1071-1084, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21689595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21689595</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21689595[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.2011.05.027" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21689595">Sopher et al. (2011)</a> generated transgenic mice expressing an approximately 13.5-kb human ATXN7 minigene construct containing SCAANT1, the alternative promoter P2A, the ATXN7 translational start site in exon 3, a pathogenic CAG expansion in exon 3, and either wildtype or mutant CTCF (<a href="/entry/604167">604167</a>)-binding sites flanking exon 3. Transgenic mice with mutant CTCF-binding sites, but not those with wildtype CTCF-binding sites, showed reduced CTCF binding, elevated ATXN7 expression, and reduced SCAANT1 expression and developed features of SCA7. Knockdown of CTCF in human retinoblastoma cells significantly reduced expression of SCAANT1 and increased ATXN7 mRNA expressed from the P2A promoter, but not from the canonical upstream promoter. Chromatin immunoprecipitation analysis revealed repressive chromatin modifications in the P2A promoter with SCAANT1 expression. <a href="#18" class="mim-tip-reference" title="Sopher, B. L., Ladd, P. D., Pineda, V. V., Libby, R. T., Sunkin, S. M., Hurley, J. B., Thienes, C. P., Gaasterland, T., Filippova, G. N., La Spada, A. R. <strong>CTCF regulates ataxin-7 expression through promotion of a convergently transcribed, antisense noncoding RNA.</strong> Neuron 70: 1071-1084, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21689595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21689595</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21689595[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.2011.05.027" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21689595">Sopher et al. (2011)</a> concluded that SCAANT1 is under positive transcriptional control by CTCF and negatively regulates ATXN7 expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21689595" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Yang, H., Liu, S., He, W.-T., Zhao, J., Jiang, L.-L., Hu, H.-Y. <strong>Aggregation of polyglutamine-expanded ataxin 7 protein specifically sequesters ubiquitin-specific protease 22 and deteriorates its deubiquitinating function in the Spt-Ada-Gcn5-acetyltransferase (SAGA) complex.</strong> J. Biol. Chem. 290: 21996-22004, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26195632/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26195632</a>] [<a href="https://doi.org/10.1074/jbc.M114.631663" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26195632">Yang et al. (2015)</a> showed that polyQ-expanded ATX7 sequestered USP22 into inclusions when overexpressed in HEK293T cells. Sequestration of USP22 by polyQ-expanded ATX7 depended on interaction between the zinc finger domain of ATX7 and the N-terminal domain of USP22 and resulted in insoluble aggregates of USP22. PolyQ expansion in ATX7 reduced the catalytic activity of USP22 and impaired the deubiquitinating function of USP22. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26195632" 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 patients with SCA7 (<a href="/entry/164500">164500</a>), <a href="#3" class="mim-tip-reference" title="David, G., Abbas, N., Stevanin, G., Durr, A., Yvert, G., Cancel, G., Weber, C., Imbert, G., Saudou, F., Antoniou, E., Drabkin, H., Gemmill, R., Giunti, P., Benomar, A., Wood, N., Ruberg, M., Agid, Y., Mandel, J.-L., Brice, A. <strong>Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansion.</strong> Nature Genet. 17: 65-70, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9288099/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9288099</a>] [<a href="https://doi.org/10.1038/ng0997-65" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9288099">David et al. (1997)</a> identified a highly unstable CAG repeat expansion of the ataxin-7 gene (<a href="#0001">607640.0001</a>). On mutated alleles, CAG repeat size was highly variable, ranging from 38 to 130 repeats, whereas on normal alleles it ranged from 7 to 17 repeats. Gonadal instability in SCA7 was greater than that observed in any of the known neurodegenerative diseases caused by translated CAG repeat expansions, and the instability was particularly striking on paternal transmission (for a detailed discussion, see 'Genetic Anticipation' in <a href="/entry/164500">164500</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9288099" 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 using constructs with tissue-specific promoters, <a href="#21" class="mim-tip-reference" title="Yvert, G., Lindenberg, K. S., Picaud, S., Landwehrmeyer, G. B., Sahel, J. -A., Mandel, J.-L. <strong>Expanded polyglutamines induce neurodegeneration and trans-neuronal alterations in cerebellum and retina of SCA7 transgenic mice.</strong> Hum. Molec. Genet. 9: 2491-2506, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11030754/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11030754</a>] [<a href="https://doi.org/10.1093/hmg/9.17.2491" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11030754">Yvert et al. (2000)</a> generated transgenic mice which expressed mutant human ataxin-7 in either Purkinje cells or retinal rod photoreceptors. Mice overexpressing full-length mutant ataxin-7(Q90) either in Purkinje cells or in rod photoreceptors had deficiencies in motor coordination and vision, respectively. In both models, an N-terminal fragment of mutant ataxin-7 accumulated within ubiquitinated nuclear inclusions that recruited a distinct set of chaperone/proteasome subunits. A severe degeneration was caused by overexpression of ataxin-7(Q90) in rods, whereas a similar overexpression of normal ataxin-7(Q10) had no obvious effect. The degenerative process was not limited to photoreceptors, and secondary alterations were seen in postsynaptic neurons. The authors suggested that proteolytic cleavage of mutant ataxin-7 and transneuronal responses are implicated in the pathogenesis of SCA7. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11030754" 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>To study the mechanism of polyglutamine neurotoxicity in SCA7, <a href="#11" class="mim-tip-reference" title="La Spada, A. R., Fu, Y.-H., Sopher, B. L., Libby, R. T., Wang, X., Li, L. Y., Einum, D. D., Huang, J., Possin, D. E., Smith, A. C., Martinez, R. A., Koszdin, K. L., Treuting, P. M., Ware, C. B., Hurley, J. B., Ptacek, L. J., Chen, S. <strong>Polyglutamine-expanded ataxin-7 antagonizes CRX function and induces cone-rod dystrophy in a mouse model of SCA7.</strong> Neuron 31: 913-927, 2001. Note: Erratum: Neuron 32: 957-958, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11580893/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11580893</a>] [<a href="https://doi.org/10.1016/s0896-6273(01)00422-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11580893">La Spada et al. (2001)</a> generated a transgenic mouse model of SCA7 that expressed ataxin-7 with 92 glutamines in the CNS and retina. They observed a cone-rod dystrophy type of retinal degeneration. Using yeast 2-hybrid studies, <a href="#11" class="mim-tip-reference" title="La Spada, A. R., Fu, Y.-H., Sopher, B. L., Libby, R. T., Wang, X., Li, L. Y., Einum, D. D., Huang, J., Possin, D. E., Smith, A. C., Martinez, R. A., Koszdin, K. L., Treuting, P. M., Ware, C. B., Hurley, J. B., Ptacek, L. J., Chen, S. <strong>Polyglutamine-expanded ataxin-7 antagonizes CRX function and induces cone-rod dystrophy in a mouse model of SCA7.</strong> Neuron 31: 913-927, 2001. Note: Erratum: Neuron 32: 957-958, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11580893/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11580893</a>] [<a href="https://doi.org/10.1016/s0896-6273(01)00422-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11580893">La Spada et al. (2001)</a> demonstrated that ataxin-7 interacts with CRX, a nuclear transcription factor predominantly expressed in retinal photoreceptor cells. Mutations in the CRX gene cause cone-rod dystrophy-2 (<a href="/entry/120970">120970</a>) in humans. Coimmunoprecipitation experiments colocalized ataxin-7 with CRX in nuclear aggregates. Using a rhodopsin promoter-reporter construct, <a href="#11" class="mim-tip-reference" title="La Spada, A. R., Fu, Y.-H., Sopher, B. L., Libby, R. T., Wang, X., Li, L. Y., Einum, D. D., Huang, J., Possin, D. E., Smith, A. C., Martinez, R. A., Koszdin, K. L., Treuting, P. M., Ware, C. B., Hurley, J. B., Ptacek, L. J., Chen, S. <strong>Polyglutamine-expanded ataxin-7 antagonizes CRX function and induces cone-rod dystrophy in a mouse model of SCA7.</strong> Neuron 31: 913-927, 2001. Note: Erratum: Neuron 32: 957-958, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11580893/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11580893</a>] [<a href="https://doi.org/10.1016/s0896-6273(01)00422-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11580893">La Spada et al. (2001)</a> observed that polyglutamine-expanded ataxin-7 suppressed CRX transactivation. With electrophoretic mobility shift assays and RT-PCR analysis, they observed a reduction in CRX binding activity and reductions in CRX-regulated genes in SCA7 transgenic retinas. The data suggested that the SCA7 transgenic mice faithfully recapitulated the process of retinal degeneration observed in human SCA7 patients. The authors hypothesized that ataxin-7-mediated transcription interference of photoreceptor-specific genes may account for the retinal degeneration in SCA7, and thus may provide an explanation for how cell-type specificity is achieved in this polyglutamine repeat disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11580893" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Helmlinger, D., Yvert, G., Picaud, S., Merienne, K., Sahel, J., Mandel, J.-L., Devys, D. <strong>Progressive retinal degeneration and dysfunction in R6 Huntington's disease mice.</strong> Hum. Molec. Genet. 11: 3351-3359, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12471061/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12471061</a>] [<a href="https://doi.org/10.1093/hmg/11.26.3351" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12471061">Helmlinger et al. (2002)</a> showed that R6 transgenic mice express mutant huntingtin (HTT; <a href="/entry/613004">613004</a>) in the retina, leading to severe vision deficiencies and retinal dystrophy. Comparable early and progressive retinal degeneration and dysfunction have been described in R7E mice (<a href="#21" class="mim-tip-reference" title="Yvert, G., Lindenberg, K. S., Picaud, S., Landwehrmeyer, G. B., Sahel, J. -A., Mandel, J.-L. <strong>Expanded polyglutamines induce neurodegeneration and trans-neuronal alterations in cerebellum and retina of SCA7 transgenic mice.</strong> Hum. Molec. Genet. 9: 2491-2506, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11030754/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11030754</a>] [<a href="https://doi.org/10.1093/hmg/9.17.2491" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11030754">Yvert et al., 2000</a>). These abnormalities are reminiscent of other retinal degeneration phenotypes (in particular rd7/rd7 mice) in which photoreceptor cell loss occurs. <a href="#8" class="mim-tip-reference" title="Helmlinger, D., Yvert, G., Picaud, S., Merienne, K., Sahel, J., Mandel, J.-L., Devys, D. <strong>Progressive retinal degeneration and dysfunction in R6 Huntington's disease mice.</strong> Hum. Molec. Genet. 11: 3351-3359, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12471061/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12471061</a>] [<a href="https://doi.org/10.1093/hmg/11.26.3351" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12471061">Helmlinger et al. (2002)</a> suggested that the NRL (<a href="/entry/162080">162080</a>) pathway and photoreceptor cell fate may be altered in the retina of R6 and R7E mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11030754+12471061" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Libby, R. T., Monckton, D. G., Fu, Y.-H., Martinez, R. A., McAbney, J. P., Lau, R., Einum, D. D., Nichol, K., Ware, C. B., Ptacek, L. J., Pearson, C. E., La Spada, A. R. <strong>Genomic context drives SCA7 CAG repeat instability, while expressed SCA7 cDNAs are intergenerationally and somatically stable in transgenic mice.</strong> Hum. Molec. Genet. 12: 41-50, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12490531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12490531</a>] [<a href="https://doi.org/10.1093/hmg/ddg006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12490531">Libby et al. (2003)</a> generated lines of transgenic mice carrying either a ATXN7 cDNA construct or a 13.5 kb ATXN7 genomic fragment with 92 CAG repeats. Whereas the cDNA transgenic mice showed little intergenerational repeat instability, the genomic fragment transgenic mice displayed marked intergenerational instability with an obvious expansion bias. Selective deletion of the 3-prime genomic region significantly stabilized intergenerational transmission of the ATXN7 92 CAG repeat. The authors suggested that cis-information present on the genomic fragment may drive the instability process. Small-pool and standard PCR analyses of tissues from genomic fragment mice revealed large repeat expansions in their brains and livers, but no such changes were found in any tissues from cDNA transgenic mice that underwent neurodegeneration. As large somatic repeat expansions were absent from the brains of ATXN7 cDNA mice, <a href="#13" class="mim-tip-reference" title="Libby, R. T., Monckton, D. G., Fu, Y.-H., Martinez, R. A., McAbney, J. P., Lau, R., Einum, D. D., Nichol, K., Ware, C. B., Ptacek, L. J., Pearson, C. E., La Spada, A. R. <strong>Genomic context drives SCA7 CAG repeat instability, while expressed SCA7 cDNAs are intergenerationally and somatically stable in transgenic mice.</strong> Hum. Molec. Genet. 12: 41-50, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12490531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12490531</a>] [<a href="https://doi.org/10.1093/hmg/ddg006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12490531">Libby et al. (2003)</a> proposed that neurodegeneration may occur without marked somatic mosaicism, at least in these mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12490531" 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="Bowman, A. B., Yoo, S.-Y., Dantuma, N. P., Zoghbi, H. Y. <strong>Neuronal dysfunction in a polyglutamine disease model occurs in the absence of ubiquitin-proteasome system impairment and inversely correlates with the degree of nuclear inclusion formation.</strong> Hum. Molec. Genet. 14: 679-691, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15661755/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15661755</a>] [<a href="https://doi.org/10.1093/hmg/ddi064" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15661755">Bowman et al. (2005)</a> assessed the ubiquitin-proteasome system (UPS) using transgenic mice with 266 CAG repeats and a ubiquitin (<a href="/entry/191339">191339</a>) reporter gene. Reporter levels were low during the initial phase of disease, suggesting that neuronal dysfunction occurs in the presence of a functional UPS. Late in disease, there was a significant increase in reporter levels specific to the most vulnerable neurons, resulting from increase in ubiquitin reporter mRNA. No evidence for general UPS impairment or reduction of proteasome activity was seen. The differential increase of ubiquitin reporter among individual neurons directly correlated with the downregulation of a marker of selective pathology and neuronal dysfunction in SCA7. There was an inverse correlation between the neuropathology revealed by the reporter and ataxin-7 nuclear inclusions in the vulnerable neurons. <a href="#1" class="mim-tip-reference" title="Bowman, A. B., Yoo, S.-Y., Dantuma, N. P., Zoghbi, H. Y. <strong>Neuronal dysfunction in a polyglutamine disease model occurs in the absence of ubiquitin-proteasome system impairment and inversely correlates with the degree of nuclear inclusion formation.</strong> Hum. Molec. Genet. 14: 679-691, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15661755/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15661755</a>] [<a href="https://doi.org/10.1093/hmg/ddi064" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15661755">Bowman et al. (2005)</a> proposed a protective role for polyglutamine nuclear inclusions against neuronal dysfunction and excluded significant impairment of the UPS in polyglutamine neuropathology. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15661755" 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="Janer, A., Werner, A., Takahashi-Fujigasaki, J., Daret, A., Fujigasaki, H., Takada, K., Duyckaerts, C., Brice, A., Dejean, A., Sittler, A. <strong>SUMOylation attenuates the aggregation propensity and cellular toxicity of the polyglutamine expanded ataxin-7.</strong> Hum. Molec. Genet. 19: 181-195, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19843541/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19843541</a>] [<a href="https://doi.org/10.1093/hmg/ddp478" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19843541">Janer et al. (2010)</a> identified ATXN7 as target for sumoylation in vitro and in vivo. Sumoylation did not influence the subcellular localization of ATXN7 nor its interaction with components of the TFTC/STAGA complex. Expansion of the polyglutamine stretch did not impair the sumoylation of ATXN7. SUMO1 (<a href="/entry/601912">601912</a>) and SUMO2 (<a href="/entry/603042">603042</a>) colocalized with ATXN7 in a subset of neuronal intranuclear inclusions in the brain of SCA7 patients and Atxn7 knockin mice. In a COS-7 cellular model of SCA7, there were 2 populations of extranuclear inclusions: homogeneous and nonhomogeneous. Nonhomogeneous inclusions showed significantly reduced colocalization with SUMO1 and SUMO2, but were highly enriched in Hsp70 (HSPA1A; <a href="/entry/140550">140550</a>), 19S proteasome, and ubiquitin. These were characterized by increased staining with the apoptotic marker caspase-3 (CASP3; <a href="/entry/600636">600636</a>) and by disruption of PML nuclear bodies (see <a href="/entry/102578">102578</a>). Preventing the sumoylation of expanded ATXN7 by mutating the SUMO site increased both the amount of SDS-insoluble aggregates and of CASP3-positive nonhomogeneous inclusions, which are toxic to the cells. <a href="#9" class="mim-tip-reference" title="Janer, A., Werner, A., Takahashi-Fujigasaki, J., Daret, A., Fujigasaki, H., Takada, K., Duyckaerts, C., Brice, A., Dejean, A., Sittler, A. <strong>SUMOylation attenuates the aggregation propensity and cellular toxicity of the polyglutamine expanded ataxin-7.</strong> Hum. Molec. Genet. 19: 181-195, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19843541/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19843541</a>] [<a href="https://doi.org/10.1093/hmg/ddp478" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19843541">Janer et al. (2010)</a> concluded that sumoylation influences the multistep aggregation process of ATXN7, and they implicated a role for ATXN7 sumoylation in SCA7 pathogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19843541" 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 18 patients from 5 families with spinocerebellar ataxia-7 (SCA7; <a href="/entry/164500">164500</a>), <a href="#3" class="mim-tip-reference" title="David, G., Abbas, N., Stevanin, G., Durr, A., Yvert, G., Cancel, G., Weber, C., Imbert, G., Saudou, F., Antoniou, E., Drabkin, H., Gemmill, R., Giunti, P., Benomar, A., Wood, N., Ruberg, M., Agid, Y., Mandel, J.-L., Brice, A. <strong>Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansion.</strong> Nature Genet. 17: 65-70, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9288099/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9288099</a>] [<a href="https://doi.org/10.1038/ng0997-65" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9288099">David et al. (1997)</a> reported a highly unstable CAG repeat expansion of the ataxin-7 gene. Gonadal instability was pronounced and was associated with paternal transmission. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9288099" 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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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15661755/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15661755</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15661755" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddi064" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Chen2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chen, S., Peng, G.-H., Wang, X., Smith, A. C., Grote, S. K., Sopher, B. L., La Spada, A. R.
|
|
<strong>Interference of Crx-dependent transcription by ataxin-7 involves interaction between the glutamine regions and requires the ataxin-7 carboxy-terminal region for nuclear localization.</strong>
|
|
Hum. Molec. Genet. 13: 53-67, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14613968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14613968</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14613968" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddh005" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="David1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
David, G., Abbas, N., Stevanin, G., Durr, A., Yvert, G., Cancel, G., Weber, C., Imbert, G., Saudou, F., Antoniou, E., Drabkin, H., Gemmill, R., Giunti, P., Benomar, A., Wood, N., Ruberg, M., Agid, Y., Mandel, J.-L., Brice, A.
|
|
<strong>Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansion.</strong>
|
|
Nature Genet. 17: 65-70, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9288099/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9288099</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9288099" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng0997-65" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Einum2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Einum, D. D., Clark, A. M., Townsend, J. J., Ptacek, L. J., Fu, Y.-H.
|
|
<strong>A novel central nervous system-enriched spinocerebellar ataxia type 7 gene product.</strong>
|
|
Arch. Neurol. 60: 97-103, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12533095/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12533095</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12533095" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1001/archneur.60.1.97" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Gavin2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gavin, A. C., Bosche, M., Krause, R., Grandi, P., Marzioch, M., Bauer, A., Schultz, J., Rick, J. M., Michon, A. M., Cruciat, C.-M., Remor, M., Hofert, C., and 26 others.
|
|
<strong>Functional organization of the yeast proteome by systematic analysis of protein complexes.</strong>
|
|
Nature 415: 141-147, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11805826/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11805826</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11805826" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/415141a" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Gross2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gross, M. B.
|
|
<strong>Personal Communication.</strong>
|
|
Baltimore, Md. 2/14/2012.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Helmlinger2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Helmlinger, D., Hardy, S., Sasorith, S., Klein, F., Robert, F., Weber, C., Miguet, L., Potier, N., Van-Dorsselaer, A., Wurtz, J.-M., Mandel, J.-L., Tora, L., Devys, D.
|
|
<strong>Ataxin-7 is a subunit of GCN5 histone acetyltransferase-containing complexes.</strong>
|
|
Hum. Molec. Genet. 13: 1257-1265, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15115762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15115762</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15115762" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddh139" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Helmlinger2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Helmlinger, D., Yvert, G., Picaud, S., Merienne, K., Sahel, J., Mandel, J.-L., Devys, D.
|
|
<strong>Progressive retinal degeneration and dysfunction in R6 Huntington's disease mice.</strong>
|
|
Hum. Molec. Genet. 11: 3351-3359, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12471061/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12471061</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12471061" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/11.26.3351" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Janer2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Janer, A., Werner, A., Takahashi-Fujigasaki, J., Daret, A., Fujigasaki, H., Takada, K., Duyckaerts, C., Brice, A., Dejean, A., Sittler, A.
|
|
<strong>SUMOylation attenuates the aggregation propensity and cellular toxicity of the polyglutamine expanded ataxin-7.</strong>
|
|
Hum. Molec. Genet. 19: 181-195, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19843541/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19843541</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19843541" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddp478" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Kaytor1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kaytor, M. D., Duvick, L. A., Skinner, P. J., Koob, M. D., Ranum, L. P. W., Orr, H. T.
|
|
<strong>Nuclear localization of the spinocerebellar ataxia type 7 protein, ataxin-7.</strong>
|
|
Hum. Molec. Genet. 8: 1657-1664, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10441328/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10441328</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10441328" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/8.9.1657" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="La Spada2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
La Spada, A. R., Fu, Y.-H., Sopher, B. L., Libby, R. T., Wang, X., Li, L. Y., Einum, D. D., Huang, J., Possin, D. E., Smith, A. C., Martinez, R. A., Koszdin, K. L., Treuting, P. M., Ware, C. B., Hurley, J. B., Ptacek, L. J., Chen, S.
|
|
<strong>Polyglutamine-expanded ataxin-7 antagonizes CRX function and induces cone-rod dystrophy in a mouse model of SCA7.</strong>
|
|
Neuron 31: 913-927, 2001. Note: Erratum: Neuron 32: 957-958, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11580893/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11580893</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11580893" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0896-6273(01)00422-6" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Lebre2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lebre, A.-S., Jamot, L., Takahashi, J., Spassky, N., Leprince, C., Ravise, N., Zander, C., Fujigasaki, H., Kussel-Andermann, P., Duyckaerts, C., Camonis, J. H., Brice, A.
|
|
<strong>Ataxin-7 interacts with a Cbl-associated protein that it recruits into neuronal intranuclear inclusions.</strong>
|
|
Hum. Molec. Genet. 10: 1201-1213, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11371513/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11371513</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11371513" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/10.11.1201" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Libby2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Libby, R. T., Monckton, D. G., Fu, Y.-H., Martinez, R. A., McAbney, J. P., Lau, R., Einum, D. D., Nichol, K., Ware, C. B., Ptacek, L. J., Pearson, C. E., La Spada, A. R.
|
|
<strong>Genomic context drives SCA7 CAG repeat instability, while expressed SCA7 cDNAs are intergenerationally and somatically stable in transgenic mice.</strong>
|
|
Hum. Molec. Genet. 12: 41-50, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12490531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12490531</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12490531" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddg006" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Matilla2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Matilla, A., Gorbea, C., Einum, D. D., Townsend, J., Michalik, A., van Broeckhoven, C., Jensen, C. C., Murphy, K. J., Ptacek, L. J., Fu, Y.-H.
|
|
<strong>Association of ataxin-7 with the proteasome subunit S4 of the 19S regulatory complex.</strong>
|
|
Hum. Molec. Genet. 10: 2821-2831, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11734547/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11734547</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11734547" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/10.24.2821" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Michalik1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Michalik, A., Del-Favero, J., Mauger, C., Lofgren, A., Van Broeckhoven, C.
|
|
<strong>Genomic organisation of the spinocerebellar ataxia type 7 (SCA7) gene responsible for autosomal dominant cerebellar ataxia with retinal degeneration.</strong>
|
|
Hum. Genet. 105: 410-417, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10598805/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10598805</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10598805" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s004390051123" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Sanders2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sanders, S. L., Jennings, J., Canutescu, A., Link, A. J., Weil, P. A.
|
|
<strong>Proteomics of the eukaryotic transcription machinery: identification of proteins associated with components of yeast TFIID by multidimensional mass spectrometry.</strong>
|
|
Molec. Cell. Biol. 22: 4723-4738, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12052880/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12052880</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12052880[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=12052880" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1128/MCB.22.13.4723-4738.2002" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Scheel2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Scheel, H., Tomiuk, S., Hofmann, K.
|
|
<strong>Elucidation of ataxin-3 and ataxin-7 function by integrative bioinformatics.</strong>
|
|
Hum. Molec. Genet. 12: 2845-2852, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12944423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12944423</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12944423" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddg297" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Sopher2011" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Sopher, B. L., Ladd, P. D., Pineda, V. V., Libby, R. T., Sunkin, S. M., Hurley, J. B., Thienes, C. P., Gaasterland, T., Filippova, G. N., La Spada, A. R.
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<strong>CTCF regulates ataxin-7 expression through promotion of a convergently transcribed, antisense noncoding RNA.</strong>
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Neuron 70: 1071-1084, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21689595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21689595</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21689595[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=21689595" 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.2011.05.027" target="_blank">Full Text</a>]
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</p>
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<a id="19" class="mim-anchor"></a>
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<a id="Strom2002" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Strom, A.-L., Jonasson, J., Hart, P., Brannstrom, T., Forsgren, L., Holmberg, M.
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<strong>Cloning and expression analysis of the murine homolog of the spinocerebellar ataxia type 7 (SCA7) gene.</strong>
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Gene 285: 91-99, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12039035/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12039035</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12039035" 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/s0378-1119(02)00399-2" 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="20" class="mim-anchor"></a>
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<a id="Yang2015" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yang, H., Liu, S., He, W.-T., Zhao, J., Jiang, L.-L., Hu, H.-Y.
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<strong>Aggregation of polyglutamine-expanded ataxin 7 protein specifically sequesters ubiquitin-specific protease 22 and deteriorates its deubiquitinating function in the Spt-Ada-Gcn5-acetyltransferase (SAGA) complex.</strong>
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J. Biol. Chem. 290: 21996-22004, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26195632/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26195632</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26195632" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.M114.631663" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="21" class="mim-anchor"></a>
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<a id="Yvert2000" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yvert, G., Lindenberg, K. S., Picaud, S., Landwehrmeyer, G. B., Sahel, J. -A., Mandel, J.-L.
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<strong>Expanded polyglutamines induce neurodegeneration and trans-neuronal alterations in cerebellum and retina of SCA7 transgenic mice.</strong>
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Hum. Molec. Genet. 9: 2491-2506, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11030754/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11030754</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11030754" 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/hmg/9.17.2491" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="22" class="mim-anchor"></a>
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<a id="Zander2001" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zander, C., Takahashi, J., El Hachimi, K. H., Fujigasaki, H., Albanese, V., Lebre, A. S., Stevanin, G., Duyckaerts, C., Brice, A.
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<strong>Similarities between spinocerebellar ataxia type 7 (SCA7) cell models and human brain: proteins recruited in inclusions and activation of caspase-3.</strong>
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Hum. Molec. Genet. 10: 2569-2579, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11709544/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11709544</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11709544" 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/hmg/10.22.2569" target="_blank">Full Text</a>]
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</p>
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</ol>
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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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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Bao Lige - updated : 12/10/2020
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Matthew B. Gross - updated : 2/14/2012<br>Patricia A. Hartz - updated : 2/10/2012<br>George E. Tiller - updated : 11/12/2010<br>George E. Tiller - updated : 2/5/2008<br>George E. Tiller - updated : 2/17/2006<br>George E. Tiller - updated : 1/31/2006<br>George E. Tiller - updated : 10/26/2004<br>George E. Tiller - updated : 9/10/2004<br>George E. Tiller - updated : 8/19/2004<br>Cassandra L. Kniffin - updated : 3/21/2003
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</span>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</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 : 3/19/2003
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<a id="editHistory" class="mim-anchor"></a>
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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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</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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mgross : 12/10/2020
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</span>
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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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carol : 11/07/2019<br>carol : 05/07/2016<br>mgross : 2/15/2012<br>mgross : 2/14/2012<br>mgross : 2/14/2012<br>mgross : 2/14/2012<br>terry : 2/10/2012<br>wwang : 11/22/2010<br>terry : 11/12/2010<br>wwang : 9/15/2009<br>wwang : 4/27/2009<br>wwang : 2/13/2008<br>terry : 2/5/2008<br>wwang : 3/6/2006<br>terry : 2/17/2006<br>wwang : 2/7/2006<br>terry : 2/3/2006<br>terry : 1/31/2006<br>tkritzer : 11/8/2004<br>tkritzer : 10/26/2004<br>tkritzer : 9/20/2004<br>tkritzer : 9/10/2004<br>alopez : 8/19/2004<br>carol : 4/3/2003<br>ckniffin : 3/21/2003
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</span>
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<div class="container visible-print-block">
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 607640
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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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ATAXIN 7; ATXN7
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</span>
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</h3>
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</div>
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<div>
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<br />
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: ATXN7</em></strong>
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</span>
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</p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 715726000;
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</span>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 3p14.1
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Genomic coordinates <span class="small">(GRCh38)</span> : 3:63,863,144-64,003,462 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<td rowspan="1">
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<span class="mim-font">
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3p14.1
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<td>
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<span class="mim-font">
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Spinocerebellar ataxia 7
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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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164500
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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<br />
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>ATXN7 is a transcription factor that appears to be critically important for chromatin remodeling at the level of histone acetylation and deubiquitination. It is a core component of 2 different transcription coactivator complexes: the SPT3 (SUPT3H; 602947)/TAF9 (600822)/GCN5 (KAT2A; 602301) acetyltransferase (STAGA) complex, which has histone acetyltransferase activity, and the USP22 (612116) deubiquitination complex (summary by Sopher et al., 2011). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By positional cloning, David et al. (1997) identified the causative gene for spinocerebellar ataxia-7 (164500). The ATXN7 gene has a 2,727-bp open reading frame predicting an 892-amino acid polypeptide, designated ataxin-7, with a nuclear localization signal and a polyglutamine (polyQ) tract. In the consensus cDNA sequence, a 9-residue polyglutamine tract is encoded by CAG repeats at codons 30 to 39. Mutated disease alleles have expanded repeats (see MOLECULAR GENETICS). </p><p>Einum et al. (2003) identified an ATXN7 splice variant, termed ataxin-7b, which contains an additional 67 basepairs between exons 12 and 13, and predicts a 945-amino acid protein with a molecular mass of 101 kD. Northern blot analysis revealed a 4.5-kb transcript expressed predominantly throughout the CNS. Immunohistochemistry revealed intense cytoplasmic staining in cerebellar Purkinje cells, inferior olivary neurons, and retinal photoreceptor cells. Einum et al. (2003) suggested that expanded polyglutamine repeats in ataxin-7b also contribute to neurodegeneration and that expression of multiple polyglutamine-containing proteins may result in selective patterns of neurodegeneration. </p><p>Sopher et al. (2011) identified human ATXN7 variants that initiate from an alternative promoter (P2A) and transcription start site in the 3-prime end of intron 2. These variants differ from previously reported ATXN7 transcripts in their 5-prime UTR, but the translational start site is unchanged. </p><p>Strom et al. (2002) cloned the mouse Sca7 cDNA from a brain cDNA library. The deduced 867-amino acid protein shows 88.7% identity with the human protein. The mouse CAG region contained only 5 repeats in 3 different strains examined. Northern blot analysis detected expression of Sca7 in all adult mouse tissues, with highest expression in heart, brain, liver, and kidney. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Michalik et al. (1999) reported that the ATXN7 gene contains 13 exons that range in size from 69 to 979 bp. The ATG initiation codon at position 554 of the cDNA occurs in exon 3 at position 12, and the coding region extends to the first 5 codons of exon 13. The CAG repeat is located in exon 3, starting at codon 30. The introns vary in size from 233 bp to about 40 kb, resulting in an overall size for the ATXN7 gene of about 140 kb. Sequence analysis of intron 7 (491 bp) revealed a polymorphic GT/AC repeat, a useful intragenic marker for ATXN7 in segregation studies. </p><p>Sopher et al. (2011) identified an alternative promoter (P2A) in ATXN7 that initiates transcription at an alternate start site in the 3-prime end of intron 2. Variants initiated from P2A contain a single first exon comprising the last 400 bp of intron 2 and exon 3, or instead have a shorter exon (2A) spliced to exon 3. The translational start site is unchanged. Binding sites for the transcriptional regulator CTCF (604167) flank exon 3. Mice have a single Atxn7 promoter corresponding to human P2A. Sopher et al. (2011) also identified identified SCAANT1 (ATXN7AS1; 614481), an ATXN7 antisense transcript on the opposite strand. SCAANT1 transcription begins in ATXN7 intron 4 and covers exon 4, exon 3, including the translational start site and the CAG repeat region, and the P2A promoter of ATXN7. </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>Gross (2012) mapped the ATXN7 gene to chromosome 3p14.1 based on an alignment of the ATXN7 sequence (GenBank AF032105) with the genomic sequence (GRCh37).</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>Kaytor et al. (1999) examined the subcellular localization of ataxin-7 in transfected COS-1 cells, using ATXN7 cDNA clones with different CAG repeat tract lengths. In addition to a diffuse distribution throughout the nucleus, ataxin-7 associated with the nuclear matrix and the nucleolus. The location of the putative ATXN7 nuclear localization sequence (NLS) was confirmed by fusing an ataxin-7 fragment with chicken muscle pyruvate kinase, a normally cytoplasmic protein. Mutation of this NLS prevented protein from entering the nucleus. Thus, expanded ataxin-7 may carry out its pathogenic effects in the nucleus by altering a matrix-associated nuclear structure and/or by disrupting nucleolar function. </p><p>Lebre et al. (2001) used a 2-hybrid approach to screen a human retina cDNA library for ataxin-7-binding proteins and isolated R85, a splice variant of Cbl-associated protein (CAP; 605264). R85 and CAP are generated by alternative splicing of the SH3P12 gene, which was localized on chromosome 10q23-q24. The interaction between ataxin-7 and the SH3P12 gene products was confirmed by pull-down and coimmunoprecipitation. SH3P12 gene products are expressed in Purkinje cells in the cerebellum. Ataxin-7 colocalizes with full-length R85 in cotransfected COS-7 cells and with one of the SH3P12 gene products in neuronal intranuclear inclusions in brain from a SCA7 patient. The authors proposed that this interaction may be part of a physiologic pathway related to the function or turnover of ataxin-7. </p><p>To analyze the effects of overexpression of mutant ataxin-7 protein, Zander et al. (2001) established ATXN7 cell culture models in kidney and neuroblastoma cell lines. The cells readily formed anti-ataxin-7-positive fibrillar inclusions and small, nuclear electron-dense structures. Comparable to the inclusions in human SCA7 brain tissue, there were consistent signs of ongoing abnormal protein folding, including the recruitment of heat-shock proteins and proteasome subunits. Occasionally, sequestered transcription factors were found. Activated caspase-3 (600636) was recruited into the inclusions in both the cell models and human SCA7 brain, and its expression was upregulated in cortical neurons, suggesting that it may play a role in the disease process. On the ultrastructural level, there were signs of autophagy and nuclear indentations, indicative of a major stress response in cells expressing mutant ataxin-7. </p><p>Matilla et al. (2001) used a 2-hybrid assay to show that ataxin-7 interacts with the ATPase subunit S4 of the 19S regulatory complex of the 26S proteasome (602706). The ataxin-7/S4 association was modulated by the length of the polyglutamine tract, whereby S4 showed a stronger association with the wildtype allele of ataxin-7. Endogenous ataxin-7 localized to discrete nuclear foci that also contained additional components of the proteasomal complex. Immunohistochemical analyses suggested alterations either of the distribution or the levels of S4 immunoreactivity in neurons that degenerate in SCA7 brains. Immunoblot analyses demonstrated reduced levels of S4 in SCA7 cerebella without evident alterations in the levels of other proteasome subunits. The authors suggested a role for S4 and ubiquitin-mediated proteasomal proteolysis in the molecular pathogenesis of SCA7. </p><p>By combining profile-based sequence analysis with genomewide functional data in model organisms, Scheel et al. (2003) found that ATXN7 is orthologous to the yeast open reading frame Ygl066c. Evidence suggested that Ygl066c is a component of the SAGA histone acetyltransferase complex. Scheel et al. (2003) suggested the finding had implications for disease pathogenesis by providing a direct connection between SCA7 and histone acetylation. </p><p>A putative ataxin-7 yeast ortholog, SGF73 (Ygl066c), is a component of the SAGA (Spt/Ada/Gcn5 acetylase) multisubunit complex, a coactivator required for transcription of a subset of RNA polymerase II (see 180660)-dependent genes (Gavin et al., 2002; Sanders et al., 2002). Helmlinger et al. (2004) showed that ataxin-7 is an integral component of the mammalian SAGA-like complexes TFTC (TATA-binding protein-free TAF-containing complex) and STAGA (SPT3 (602947)/TAF9 (600822)/GCN5 (602301) acetyltransferase complex). Immunopurified ataxin-7 complex retained histone acetyltransferase (see 603053) activity, characteristic for TFTC-like complexes. The authors identified a 71-amino acid domain in ataxin-7 that is required for interaction with TFTC/STAGA subunits and is conserved highly through evolution, allowing the identification of a ATXN7 gene family. This domain contains a conserved cys3-his motif that binds zinc, forming a new zinc-binding domain. Polyglutamine expansion in ataxin-7 did not affect its incorporation into TFTC/STAGA complexes purified from SCA7 patient cells. The authors concluded that ataxin-7 is the human ortholog of the yeast SAGA SGF73 subunit and is a bona fide subunit of the human TFTC-like transcriptional complexes. </p><p>In an SCA7 transgenic mouse model, La Spada et al. (2001) found that the cone-rod dystrophy involved altered photoreceptor gene expression due to interference with CRX (602225), a homeodomain transcription factor containing a glutamine-rich region. By coimmunoprecipitation analysis of CRX and ATXN7 truncation and point mutants, Chen et al. (2004) determined that the ATXN7-interacting domain of CRX localized to its glutamine-rich region and the CRX-interacting domain of ATXN7 localized to its glutamine tract. Nuclear localization of ataxin-7 was required to repress Crx transactivation, and the likely nuclear localization signals were mapped to the C-terminal region of ataxin-7. Using chromatin immunoprecipitation, the authors showed that both Crx and ataxin-7 occupied the promoter and enhancer regions of Crx-regulated retinal genes in vivo. Chen et al. (2004) suggested that one mechanism of SCA7 disease pathogenesis may be transcription dysregulation, and that CRX transcription interference may be a predominant factor in SCA7 cone-rod dystrophy retinal degeneration. </p><p><strong><em>Regulation of ATXN7 by ATXN7AS1</em></strong></p><p>
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By quantitative RT-PCR of human human tissues, Sopher et al. (2011) observed inverse expression of ATXN7 and its antisense transcript, SCAANT1 (ATXN7AS1; 614481). ATXN7 expression was high in cortex, cerebellum, striatum, and liver and weak in lung and kidney, whereas SCAANT1 expression was weak in brain tissues and liver and high in lung and kidney. Qualitative RT-PCR revealed abnormally elevated ATXN7 expression and reduced SCAANT1 expression in SCA7 patient fibroblasts and peripheral blood samples. Sopher et al. (2011) generated transgenic mice expressing an approximately 13.5-kb human ATXN7 minigene construct containing SCAANT1, the alternative promoter P2A, the ATXN7 translational start site in exon 3, a pathogenic CAG expansion in exon 3, and either wildtype or mutant CTCF (604167)-binding sites flanking exon 3. Transgenic mice with mutant CTCF-binding sites, but not those with wildtype CTCF-binding sites, showed reduced CTCF binding, elevated ATXN7 expression, and reduced SCAANT1 expression and developed features of SCA7. Knockdown of CTCF in human retinoblastoma cells significantly reduced expression of SCAANT1 and increased ATXN7 mRNA expressed from the P2A promoter, but not from the canonical upstream promoter. Chromatin immunoprecipitation analysis revealed repressive chromatin modifications in the P2A promoter with SCAANT1 expression. Sopher et al. (2011) concluded that SCAANT1 is under positive transcriptional control by CTCF and negatively regulates ATXN7 expression. </p><p>Yang et al. (2015) showed that polyQ-expanded ATX7 sequestered USP22 into inclusions when overexpressed in HEK293T cells. Sequestration of USP22 by polyQ-expanded ATX7 depended on interaction between the zinc finger domain of ATX7 and the N-terminal domain of USP22 and resulted in insoluble aggregates of USP22. PolyQ expansion in ATX7 reduced the catalytic activity of USP22 and impaired the deubiquitinating function of USP22. </p>
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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 class="mim-text-font">
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<p>In patients with SCA7 (164500), David et al. (1997) identified a highly unstable CAG repeat expansion of the ataxin-7 gene (607640.0001). On mutated alleles, CAG repeat size was highly variable, ranging from 38 to 130 repeats, whereas on normal alleles it ranged from 7 to 17 repeats. Gonadal instability in SCA7 was greater than that observed in any of the known neurodegenerative diseases caused by translated CAG repeat expansions, and the instability was particularly striking on paternal transmission (for a detailed discussion, see 'Genetic Anticipation' in 164500). </p>
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<span class="mim-font">
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<strong>Animal Model</strong>
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<p>By using constructs with tissue-specific promoters, Yvert et al. (2000) generated transgenic mice which expressed mutant human ataxin-7 in either Purkinje cells or retinal rod photoreceptors. Mice overexpressing full-length mutant ataxin-7(Q90) either in Purkinje cells or in rod photoreceptors had deficiencies in motor coordination and vision, respectively. In both models, an N-terminal fragment of mutant ataxin-7 accumulated within ubiquitinated nuclear inclusions that recruited a distinct set of chaperone/proteasome subunits. A severe degeneration was caused by overexpression of ataxin-7(Q90) in rods, whereas a similar overexpression of normal ataxin-7(Q10) had no obvious effect. The degenerative process was not limited to photoreceptors, and secondary alterations were seen in postsynaptic neurons. The authors suggested that proteolytic cleavage of mutant ataxin-7 and transneuronal responses are implicated in the pathogenesis of SCA7. </p><p>To study the mechanism of polyglutamine neurotoxicity in SCA7, La Spada et al. (2001) generated a transgenic mouse model of SCA7 that expressed ataxin-7 with 92 glutamines in the CNS and retina. They observed a cone-rod dystrophy type of retinal degeneration. Using yeast 2-hybrid studies, La Spada et al. (2001) demonstrated that ataxin-7 interacts with CRX, a nuclear transcription factor predominantly expressed in retinal photoreceptor cells. Mutations in the CRX gene cause cone-rod dystrophy-2 (120970) in humans. Coimmunoprecipitation experiments colocalized ataxin-7 with CRX in nuclear aggregates. Using a rhodopsin promoter-reporter construct, La Spada et al. (2001) observed that polyglutamine-expanded ataxin-7 suppressed CRX transactivation. With electrophoretic mobility shift assays and RT-PCR analysis, they observed a reduction in CRX binding activity and reductions in CRX-regulated genes in SCA7 transgenic retinas. The data suggested that the SCA7 transgenic mice faithfully recapitulated the process of retinal degeneration observed in human SCA7 patients. The authors hypothesized that ataxin-7-mediated transcription interference of photoreceptor-specific genes may account for the retinal degeneration in SCA7, and thus may provide an explanation for how cell-type specificity is achieved in this polyglutamine repeat disorder. </p><p>Helmlinger et al. (2002) showed that R6 transgenic mice express mutant huntingtin (HTT; 613004) in the retina, leading to severe vision deficiencies and retinal dystrophy. Comparable early and progressive retinal degeneration and dysfunction have been described in R7E mice (Yvert et al., 2000). These abnormalities are reminiscent of other retinal degeneration phenotypes (in particular rd7/rd7 mice) in which photoreceptor cell loss occurs. Helmlinger et al. (2002) suggested that the NRL (162080) pathway and photoreceptor cell fate may be altered in the retina of R6 and R7E mice. </p><p>Libby et al. (2003) generated lines of transgenic mice carrying either a ATXN7 cDNA construct or a 13.5 kb ATXN7 genomic fragment with 92 CAG repeats. Whereas the cDNA transgenic mice showed little intergenerational repeat instability, the genomic fragment transgenic mice displayed marked intergenerational instability with an obvious expansion bias. Selective deletion of the 3-prime genomic region significantly stabilized intergenerational transmission of the ATXN7 92 CAG repeat. The authors suggested that cis-information present on the genomic fragment may drive the instability process. Small-pool and standard PCR analyses of tissues from genomic fragment mice revealed large repeat expansions in their brains and livers, but no such changes were found in any tissues from cDNA transgenic mice that underwent neurodegeneration. As large somatic repeat expansions were absent from the brains of ATXN7 cDNA mice, Libby et al. (2003) proposed that neurodegeneration may occur without marked somatic mosaicism, at least in these mice. </p><p>Bowman et al. (2005) assessed the ubiquitin-proteasome system (UPS) using transgenic mice with 266 CAG repeats and a ubiquitin (191339) reporter gene. Reporter levels were low during the initial phase of disease, suggesting that neuronal dysfunction occurs in the presence of a functional UPS. Late in disease, there was a significant increase in reporter levels specific to the most vulnerable neurons, resulting from increase in ubiquitin reporter mRNA. No evidence for general UPS impairment or reduction of proteasome activity was seen. The differential increase of ubiquitin reporter among individual neurons directly correlated with the downregulation of a marker of selective pathology and neuronal dysfunction in SCA7. There was an inverse correlation between the neuropathology revealed by the reporter and ataxin-7 nuclear inclusions in the vulnerable neurons. Bowman et al. (2005) proposed a protective role for polyglutamine nuclear inclusions against neuronal dysfunction and excluded significant impairment of the UPS in polyglutamine neuropathology. </p><p>Janer et al. (2010) identified ATXN7 as target for sumoylation in vitro and in vivo. Sumoylation did not influence the subcellular localization of ATXN7 nor its interaction with components of the TFTC/STAGA complex. Expansion of the polyglutamine stretch did not impair the sumoylation of ATXN7. SUMO1 (601912) and SUMO2 (603042) colocalized with ATXN7 in a subset of neuronal intranuclear inclusions in the brain of SCA7 patients and Atxn7 knockin mice. In a COS-7 cellular model of SCA7, there were 2 populations of extranuclear inclusions: homogeneous and nonhomogeneous. Nonhomogeneous inclusions showed significantly reduced colocalization with SUMO1 and SUMO2, but were highly enriched in Hsp70 (HSPA1A; 140550), 19S proteasome, and ubiquitin. These were characterized by increased staining with the apoptotic marker caspase-3 (CASP3; 600636) and by disruption of PML nuclear bodies (see 102578). Preventing the sumoylation of expanded ATXN7 by mutating the SUMO site increased both the amount of SDS-insoluble aggregates and of CASP3-positive nonhomogeneous inclusions, which are toxic to the cells. Janer et al. (2010) concluded that sumoylation influences the multistep aggregation process of ATXN7, and they implicated a role for ATXN7 sumoylation in SCA7 pathogenesis. </p>
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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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<h4>
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<span class="mim-font">
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<strong>.0001 SPINOCEREBELLAR ATAXIA 7</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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ATXN7, (CAG)n REPEAT EXPANSION
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<br />
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SNP: rs193922929,
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ClinVar: RCV000003087, RCV001256206
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<span class="mim-text-font">
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<p>In 18 patients from 5 families with spinocerebellar ataxia-7 (SCA7; 164500), David et al. (1997) reported a highly unstable CAG repeat expansion of the ataxin-7 gene. Gonadal instability was pronounced and was associated with paternal transmission. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<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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Bowman, A. B., Yoo, S.-Y., Dantuma, N. P., Zoghbi, H. Y.
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<strong>Neuronal dysfunction in a polyglutamine disease model occurs in the absence of ubiquitin-proteasome system impairment and inversely correlates with the degree of nuclear inclusion formation.</strong>
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Hum. Molec. Genet. 14: 679-691, 2005.
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[PubMed: 15661755]
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[Full Text: https://doi.org/10.1093/hmg/ddi064]
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</p>
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</li>
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<p class="mim-text-font">
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Chen, S., Peng, G.-H., Wang, X., Smith, A. C., Grote, S. K., Sopher, B. L., La Spada, A. R.
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<strong>Interference of Crx-dependent transcription by ataxin-7 involves interaction between the glutamine regions and requires the ataxin-7 carboxy-terminal region for nuclear localization.</strong>
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Hum. Molec. Genet. 13: 53-67, 2004.
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[PubMed: 14613968]
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[Full Text: https://doi.org/10.1093/hmg/ddh005]
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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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David, G., Abbas, N., Stevanin, G., Durr, A., Yvert, G., Cancel, G., Weber, C., Imbert, G., Saudou, F., Antoniou, E., Drabkin, H., Gemmill, R., Giunti, P., Benomar, A., Wood, N., Ruberg, M., Agid, Y., Mandel, J.-L., Brice, A.
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<strong>Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansion.</strong>
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Nature Genet. 17: 65-70, 1997.
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[PubMed: 9288099]
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[Full Text: https://doi.org/10.1038/ng0997-65]
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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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Einum, D. D., Clark, A. M., Townsend, J. J., Ptacek, L. J., Fu, Y.-H.
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<strong>A novel central nervous system-enriched spinocerebellar ataxia type 7 gene product.</strong>
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Arch. Neurol. 60: 97-103, 2003.
|
|
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[PubMed: 12533095]
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[Full Text: https://doi.org/10.1001/archneur.60.1.97]
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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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Gavin, A. C., Bosche, M., Krause, R., Grandi, P., Marzioch, M., Bauer, A., Schultz, J., Rick, J. M., Michon, A. M., Cruciat, C.-M., Remor, M., Hofert, C., and 26 others.
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<strong>Functional organization of the yeast proteome by systematic analysis of protein complexes.</strong>
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Nature 415: 141-147, 2002.
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[PubMed: 11805826]
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[Full Text: https://doi.org/10.1038/415141a]
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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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Gross, M. B.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 2/14/2012.
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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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Helmlinger, D., Hardy, S., Sasorith, S., Klein, F., Robert, F., Weber, C., Miguet, L., Potier, N., Van-Dorsselaer, A., Wurtz, J.-M., Mandel, J.-L., Tora, L., Devys, D.
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<strong>Ataxin-7 is a subunit of GCN5 histone acetyltransferase-containing complexes.</strong>
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Hum. Molec. Genet. 13: 1257-1265, 2004.
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[PubMed: 15115762]
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[Full Text: https://doi.org/10.1093/hmg/ddh139]
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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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Helmlinger, D., Yvert, G., Picaud, S., Merienne, K., Sahel, J., Mandel, J.-L., Devys, D.
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<strong>Progressive retinal degeneration and dysfunction in R6 Huntington's disease mice.</strong>
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Hum. Molec. Genet. 11: 3351-3359, 2002.
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[PubMed: 12471061]
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[Full Text: https://doi.org/10.1093/hmg/11.26.3351]
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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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Janer, A., Werner, A., Takahashi-Fujigasaki, J., Daret, A., Fujigasaki, H., Takada, K., Duyckaerts, C., Brice, A., Dejean, A., Sittler, A.
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<strong>SUMOylation attenuates the aggregation propensity and cellular toxicity of the polyglutamine expanded ataxin-7.</strong>
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Hum. Molec. Genet. 19: 181-195, 2010.
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[PubMed: 19843541]
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[Full Text: https://doi.org/10.1093/hmg/ddp478]
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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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Kaytor, M. D., Duvick, L. A., Skinner, P. J., Koob, M. D., Ranum, L. P. W., Orr, H. T.
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<strong>Nuclear localization of the spinocerebellar ataxia type 7 protein, ataxin-7.</strong>
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Hum. Molec. Genet. 8: 1657-1664, 1999.
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[PubMed: 10441328]
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[Full Text: https://doi.org/10.1093/hmg/8.9.1657]
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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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La Spada, A. R., Fu, Y.-H., Sopher, B. L., Libby, R. T., Wang, X., Li, L. Y., Einum, D. D., Huang, J., Possin, D. E., Smith, A. C., Martinez, R. A., Koszdin, K. L., Treuting, P. M., Ware, C. B., Hurley, J. B., Ptacek, L. J., Chen, S.
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<strong>Polyglutamine-expanded ataxin-7 antagonizes CRX function and induces cone-rod dystrophy in a mouse model of SCA7.</strong>
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Neuron 31: 913-927, 2001. Note: Erratum: Neuron 32: 957-958, 2001.
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[PubMed: 11580893]
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[Full Text: https://doi.org/10.1016/s0896-6273(01)00422-6]
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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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Lebre, A.-S., Jamot, L., Takahashi, J., Spassky, N., Leprince, C., Ravise, N., Zander, C., Fujigasaki, H., Kussel-Andermann, P., Duyckaerts, C., Camonis, J. H., Brice, A.
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<strong>Ataxin-7 interacts with a Cbl-associated protein that it recruits into neuronal intranuclear inclusions.</strong>
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Hum. Molec. Genet. 10: 1201-1213, 2001.
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[PubMed: 11371513]
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[Full Text: https://doi.org/10.1093/hmg/10.11.1201]
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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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Libby, R. T., Monckton, D. G., Fu, Y.-H., Martinez, R. A., McAbney, J. P., Lau, R., Einum, D. D., Nichol, K., Ware, C. B., Ptacek, L. J., Pearson, C. E., La Spada, A. R.
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<strong>Genomic context drives SCA7 CAG repeat instability, while expressed SCA7 cDNAs are intergenerationally and somatically stable in transgenic mice.</strong>
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Hum. Molec. Genet. 12: 41-50, 2003.
|
|
|
|
|
|
[PubMed: 12490531]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddg006]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Matilla, A., Gorbea, C., Einum, D. D., Townsend, J., Michalik, A., van Broeckhoven, C., Jensen, C. C., Murphy, K. J., Ptacek, L. J., Fu, Y.-H.
|
|
<strong>Association of ataxin-7 with the proteasome subunit S4 of the 19S regulatory complex.</strong>
|
|
Hum. Molec. Genet. 10: 2821-2831, 2001.
|
|
|
|
|
|
[PubMed: 11734547]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/10.24.2821]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Michalik, A., Del-Favero, J., Mauger, C., Lofgren, A., Van Broeckhoven, C.
|
|
<strong>Genomic organisation of the spinocerebellar ataxia type 7 (SCA7) gene responsible for autosomal dominant cerebellar ataxia with retinal degeneration.</strong>
|
|
Hum. Genet. 105: 410-417, 1999.
|
|
|
|
|
|
[PubMed: 10598805]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s004390051123]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sanders, S. L., Jennings, J., Canutescu, A., Link, A. J., Weil, P. A.
|
|
<strong>Proteomics of the eukaryotic transcription machinery: identification of proteins associated with components of yeast TFIID by multidimensional mass spectrometry.</strong>
|
|
Molec. Cell. Biol. 22: 4723-4738, 2002.
|
|
|
|
|
|
[PubMed: 12052880]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1128/MCB.22.13.4723-4738.2002]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Scheel, H., Tomiuk, S., Hofmann, K.
|
|
<strong>Elucidation of ataxin-3 and ataxin-7 function by integrative bioinformatics.</strong>
|
|
Hum. Molec. Genet. 12: 2845-2852, 2003.
|
|
|
|
|
|
[PubMed: 12944423]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddg297]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
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Sopher, B. L., Ladd, P. D., Pineda, V. V., Libby, R. T., Sunkin, S. M., Hurley, J. B., Thienes, C. P., Gaasterland, T., Filippova, G. N., La Spada, A. R.
|
|
<strong>CTCF regulates ataxin-7 expression through promotion of a convergently transcribed, antisense noncoding RNA.</strong>
|
|
Neuron 70: 1071-1084, 2011.
|
|
|
|
|
|
[PubMed: 21689595]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.neuron.2011.05.027]
|
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|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Strom, A.-L., Jonasson, J., Hart, P., Brannstrom, T., Forsgren, L., Holmberg, M.
|
|
<strong>Cloning and expression analysis of the murine homolog of the spinocerebellar ataxia type 7 (SCA7) gene.</strong>
|
|
Gene 285: 91-99, 2002.
|
|
|
|
|
|
[PubMed: 12039035]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0378-1119(02)00399-2]
|
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|
|
</p>
|
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</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
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Yang, H., Liu, S., He, W.-T., Zhao, J., Jiang, L.-L., Hu, H.-Y.
|
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<strong>Aggregation of polyglutamine-expanded ataxin 7 protein specifically sequesters ubiquitin-specific protease 22 and deteriorates its deubiquitinating function in the Spt-Ada-Gcn5-acetyltransferase (SAGA) complex.</strong>
|
|
J. Biol. Chem. 290: 21996-22004, 2015.
|
|
|
|
|
|
[PubMed: 26195632]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M114.631663]
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</p>
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</li>
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<li>
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Yvert, G., Lindenberg, K. S., Picaud, S., Landwehrmeyer, G. B., Sahel, J. -A., Mandel, J.-L.
|
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<strong>Expanded polyglutamines induce neurodegeneration and trans-neuronal alterations in cerebellum and retina of SCA7 transgenic mice.</strong>
|
|
Hum. Molec. Genet. 9: 2491-2506, 2000.
|
|
|
|
|
|
[PubMed: 11030754]
|
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[Full Text: https://doi.org/10.1093/hmg/9.17.2491]
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Zander, C., Takahashi, J., El Hachimi, K. H., Fujigasaki, H., Albanese, V., Lebre, A. S., Stevanin, G., Duyckaerts, C., Brice, A.
|
|
<strong>Similarities between spinocerebellar ataxia type 7 (SCA7) cell models and human brain: proteins recruited in inclusions and activation of caspase-3.</strong>
|
|
Hum. Molec. Genet. 10: 2569-2579, 2001.
|
|
|
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|
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[PubMed: 11709544]
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[Full Text: https://doi.org/10.1093/hmg/10.22.2569]
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