3939 lines
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Entry
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- *601556 - ATAXIN 1; ATXN1
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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">*601556</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<li role="presentation">
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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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<li role="presentation" style="margin-left: 1em">
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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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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#evolution">Evolution</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/601556">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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</div>
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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=ENSG00000124788;t=ENST00000436367" 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=6310" 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=601556" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000124788;t=ENST00000436367" 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_000332,NM_001128164,NM_001357857,NR_152111,NR_152112,NR_152113,NR_152114" 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_001128164" 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=601556" 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=03333&isoform_id=03333_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/ATXN1" 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/529662,4262101,15029638,15778936,51479158,109658942,119575774,119575775,119575776,119575777,119575778,189491748,206729854,430740779,1276317570" 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/P54253" 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=6310" 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=ENSG00000124788;t=ENST00000436367" 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=ATXN1" 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=ATXN1" 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+6310" 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/ATXN1" 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:6310" 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/6310" 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=chr6&hgg_gene=ENST00000436367.6&hgg_start=16299112&hgg_end=16761460&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://medlineplus.gov/genetics/gene/atxn1" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=601556[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=601556[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/ENSG00000124788" 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=ATXN1" 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=ATXN1" 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=ATXN1" 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=ATXN1&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/PA34958" 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:10548" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0029907.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:104783" 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/ATXN1#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:104783" 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/6310/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=6310" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00019394;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-060503-759" 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="mimCellLines">
|
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<span class="panel-title">
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<span class="small">
|
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" 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="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</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="mimCellLinesLinksFold" 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://catalog.coriell.org/Search?q=OmimNum:601556" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
|
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</a>
|
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</span>
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</span>
|
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:6310" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=ATXN1&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> 715748006<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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601556
|
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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 1; ATXN1
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="includedTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
|
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Other entities represented in this entry:
|
|
</span>
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|
</p>
|
|
</div>
|
|
<div>
|
|
<span class="h3 mim-font">
|
|
ATXN1, ALTERNATIVE READING FRAME, INCLUDED
|
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</span>
|
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</div>
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<div>
|
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<span class="h4 mim-font">
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|
|
ALT-ATXN1, INCLUDED
|
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</span>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
|
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=ATXN1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">ATXN1</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>
|
|
Cytogenetic location: <a href="/geneMap/6/90?start=-3&limit=10&highlight=90">6p22.3</a>
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr6:16299112-16761460&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'})">6:16,299,112-16,761,460</a> </span>
|
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</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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|
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</span>
|
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</p>
|
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</div>
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
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|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/6/90?start=-3&limit=10&highlight=90">
|
|
6p22.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Spinocerebellar ataxia 1
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/164400"> 164400 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
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</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
|
</td>
|
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</tr>
|
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</tbody>
|
|
</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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<p>ATXN1 binds RNA, associates with large protein complexes, and interacts with a vast network of proteins. ATXN1 is thought to be involved in transcriptional repression and to regulate Notch (see <a href="/entry/190198">190198</a>)- and Capicua (CIC; <a href="/entry/612082">612082</a>)-controlled developmental processes (summary by <a href="#3" class="mim-tip-reference" title="Bergeron, D., Lapointe, C., Bissonnette, C., Tremblay, G., Motard, J., Roucou, X. <strong>An out-of-frame overlapping reading frame in the ataxin-1 coding sequence encodes a novel ataxin-1 interacting protein.</strong> J. Biol. Chem. 288: 21824-21835, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23760502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23760502</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23760502[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/10.1074/jbc.M113.472654" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23760502">Bergeron et al., 2013</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23760502" 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>Using DNA fragments from a cosmid clone shown to contain the CAG trinucleotide repeat identified as the cause of spinocerebellar ataxia-1 (SCA1; <a href="/entry/164400">164400</a>) by <a href="#24" class="mim-tip-reference" title="Orr, H. T., Chung, M., Banfi, S., Kwiatkowski, T. J., Jr., Servadio, A., Beaudet, A. L., McCall, A. E., Duvick, L. A., Ranum, L. P. W., Zoghbi, H. Y. <strong>Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1.</strong> Nature Genet. 4: 221-226, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8358429/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8358429</a>] [<a href="https://doi.org/10.1038/ng0793-221" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8358429">Orr et al. (1993)</a>, <a href="#1" class="mim-tip-reference" title="Banfi, S., Servadio, A., Chung, M., Kwiatkowski, T. J., Jr., McCall, A. E., Duvick, L. A., Shen, Y., Roth, E. J., Orr, H. T., Zoghbi, H. Y. <strong>Identification and characterization of the gene causing type 1 spinocerebellar ataxia.</strong> Nature Genet. 7: 513-520, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7951322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7951322</a>] [<a href="https://doi.org/10.1038/ng0894-513" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7951322">Banfi et al. (1994)</a> screened 2 human fetal brain and 1 human adult cerebellar cDNA libraries to isolate the ATXN1 transcript. <a href="#1" class="mim-tip-reference" title="Banfi, S., Servadio, A., Chung, M., Kwiatkowski, T. J., Jr., McCall, A. E., Duvick, L. A., Shen, Y., Roth, E. J., Orr, H. T., Zoghbi, H. Y. <strong>Identification and characterization of the gene causing type 1 spinocerebellar ataxia.</strong> Nature Genet. 7: 513-520, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7951322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7951322</a>] [<a href="https://doi.org/10.1038/ng0894-513" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7951322">Banfi et al. (1994)</a> demonstrated that the ATXN1 gene encodes an 816-amino acid protein with a molecular mass of 87 kD. The (CAG)n repeat, coding for a polyglutamine tract, lies within the coding region, and the protein is transcribed from both the wildtype and the CAG-expanded ATXN1 allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7951322+8358429" 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="#21" class="mim-tip-reference" title="Mizutani, A., Wang, L., Rajan, H., Vig, P. J. S., Alaynick, W. A., Thaler, J. P., Tsai, C.-C. <strong>Boat, an AXH domain protein, suppresses the cytotoxicity of mutant ataxin-1.</strong> EMBO J. 24: 3339-3351, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16121196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16121196</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16121196[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/sj.emboj.7600785" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16121196">Mizutani et al. (2005)</a> stated that the deduced 816-amino acid ATXN1 protein has an N-terminal BOAT (ATXN1L; <a href="/entry/614301">614301</a>) and ataxin-1 (NBA) domain, followed by the polyglutamine tract, a self-association region (SAR), and a C-terminal ATXN1 and HBP1 (<a href="/entry/616714">616714</a>) (AXH) domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16121196" 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 immunoblot analysis, <a href="#28" class="mim-tip-reference" title="Servadio, A., Koshy, B., Armstrong, D., Antalffy, B., Orr, H. T., Zoghbi, H. Y. <strong>Expression analysis of the ataxin-1 protein in tissues from normal and spinocerebellar ataxia type 1 individuals.</strong> Nature Genet. 10: 94-98, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7647801/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7647801</a>] [<a href="https://doi.org/10.1038/ng0595-94" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7647801">Servadio et al. (1995)</a> demonstrated that the ATXN1 protein was present in various brain regions and in nonneuronal tissues, such as heart, skeletal muscle, and liver. Whereas it was located predominantly in cytoplasm in nonneuronal tissue, it was found in nuclei in neurons of the basal ganglia, pons, and cortex, and in both cytoplasm and nuclei of Purkinje cells of the cerebellum. <a href="#28" class="mim-tip-reference" title="Servadio, A., Koshy, B., Armstrong, D., Antalffy, B., Orr, H. T., Zoghbi, H. Y. <strong>Expression analysis of the ataxin-1 protein in tissues from normal and spinocerebellar ataxia type 1 individuals.</strong> Nature Genet. 10: 94-98, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7647801/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7647801</a>] [<a href="https://doi.org/10.1038/ng0595-94" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7647801">Servadio et al. (1995)</a> found that the protein varied in its size and electrophoretic migration properties according to the size of the (CAG)n repeat. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7647801" 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>Alternative ATXN1</em></strong></p><p>
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<a href="#3" class="mim-tip-reference" title="Bergeron, D., Lapointe, C., Bissonnette, C., Tremblay, G., Motard, J., Roucou, X. <strong>An out-of-frame overlapping reading frame in the ataxin-1 coding sequence encodes a novel ataxin-1 interacting protein.</strong> J. Biol. Chem. 288: 21824-21835, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23760502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23760502</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23760502[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/10.1074/jbc.M113.472654" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23760502">Bergeron et al. (2013)</a> identified an alternative translation initiation codon in the +3 reading frame of ATXN1. Translation of alternative ATXN1 (ALT-ATXN1) begins 30 nucleotides downstream of the initiation codon of full-length ATXN1 and ends at nucleotide 587, just prior to the CAG repeat region. The deduced 185-amino acid protein has a calculated molecular mass of 21 kD. ALT-ATXN1 contains 26 proline residues distributed throughout the molecule, and it has a putative N-terminal proline-lysine (PY)-type nuclear localization signal. ALT-ATXN1 shares no sequence similarity with ATXN1. <a href="#3" class="mim-tip-reference" title="Bergeron, D., Lapointe, C., Bissonnette, C., Tremblay, G., Motard, J., Roucou, X. <strong>An out-of-frame overlapping reading frame in the ataxin-1 coding sequence encodes a novel ataxin-1 interacting protein.</strong> J. Biol. Chem. 288: 21824-21835, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23760502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23760502</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23760502[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/10.1074/jbc.M113.472654" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23760502">Bergeron et al. (2013)</a> also identified a second putative 151-amino acid ALT-ATXN1 protein that is N-terminally truncated compared with the longer ALT-ATXN1 protein. Database analysis revealed orthologs of ALT-ATXN1 in several mammalian species and in chicken. Western blot analysis detected both ATXN1 and ALT-ATXN1 in normal human cerebellum and in primary cells cultured from a glioblastoma patient. Epitope-tagged ALT-ATXN1 colocalized with ATXN1 in nuclear inclusions and in the nucleoplasm of transfected cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23760502" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#1" class="mim-tip-reference" title="Banfi, S., Servadio, A., Chung, M., Kwiatkowski, T. J., Jr., McCall, A. E., Duvick, L. A., Shen, Y., Roth, E. J., Orr, H. T., Zoghbi, H. Y. <strong>Identification and characterization of the gene causing type 1 spinocerebellar ataxia.</strong> Nature Genet. 7: 513-520, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7951322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7951322</a>] [<a href="https://doi.org/10.1038/ng0894-513" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7951322">Banfi et al. (1994)</a> determined that ATXN1 gene spans 450 kb of genomic DNA and is organized into 9 exons. The first 7 fall in the 5-prime untranslated region, whereas the last 2 contain the coding region and a 7,277 bp 3-prime untranslated region. The first 4 noncoding exons undergo alternative splicing in several tissues. These features suggest that the transcriptional and translational regulation of ataxin-1 may be complex. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7951322" 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>Detailed linkage studies of families with SCA1 established the disease locus on chromosome 6 (see <a href="/entry/164400">164400</a>), and <a href="#34" class="mim-tip-reference" title="Volz, A., Boyle, J. M., Cann, H. M., Cottingham, R. W., Orr, H. T., Ziegler, A. <strong>Report of the second international workshop on human chromosome 6.</strong> Genomics 21: 464, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8088851/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8088851</a>] [<a href="https://doi.org/10.1006/geno.1994.1302" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8088851">Volz et al. (1994)</a> reported that the ATXN1 gene had been mapped to 6p23 by in situ hybridization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8088851" 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="#28" class="mim-tip-reference" title="Servadio, A., Koshy, B., Armstrong, D., Antalffy, B., Orr, H. T., Zoghbi, H. Y. <strong>Expression analysis of the ataxin-1 protein in tissues from normal and spinocerebellar ataxia type 1 individuals.</strong> Nature Genet. 10: 94-98, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7647801/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7647801</a>] [<a href="https://doi.org/10.1038/ng0595-94" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7647801">Servadio et al. (1995)</a> mapped the mouse homolog of the ATXN1 gene to mouse chromosome 13. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7647801" 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="#28" class="mim-tip-reference" title="Servadio, A., Koshy, B., Armstrong, D., Antalffy, B., Orr, H. T., Zoghbi, H. Y. <strong>Expression analysis of the ataxin-1 protein in tissues from normal and spinocerebellar ataxia type 1 individuals.</strong> Nature Genet. 10: 94-98, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7647801/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7647801</a>] [<a href="https://doi.org/10.1038/ng0595-94" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7647801">Servadio et al. (1995)</a> found that ATXN1 protein exhibited a normal nuclear/cytoplasmic localization in cultured cells and tissues from individuals with SCA1. Thus, the data showed that the mutant expanded ATXN1 alleles are faithfully translated into proteins of apparently normal stability and distribution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7647801" 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="#7" class="mim-tip-reference" title="Cummings, C. J., Reinstein, E., Sun, Y., Antalffy, B., Jiang, Y., Ciechanover, A., Orr, H. T., Beaudet, A. L., Zoghbi, H. Y. <strong>Mutation of the E6-AP ubiquitin ligase reduces nuclear inclusion frequency while accelerating polyglutamine-induced pathology in SCA1 mice.</strong> Neuron 24: 879-892, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10624951/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10624951</a>] [<a href="https://doi.org/10.1016/s0896-6273(00)81035-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10624951">Cummings et al. (1999)</a> found that wildtype ataxin-1 and mutant ataxin-1 with an expanded polyglutamine tract were polyubiquitinated equally well in transfected HeLa cells in vitro, but the mutant form was 3 times more resistant to degradation. Inhibiting proteasomal degradation promoted aggregation of mutant ataxin-1. Mouse Purkinje cells expressing mutant ataxin-1 but not the ubiquitin-protein ligase Ube3a (<a href="/entry/601623">601623</a>) showed fewer ubiquitin-positive nuclear inclusions than Sca1 mice, but the Purkinje cell pathology was markedly worse. <a href="#7" class="mim-tip-reference" title="Cummings, C. J., Reinstein, E., Sun, Y., Antalffy, B., Jiang, Y., Ciechanover, A., Orr, H. T., Beaudet, A. L., Zoghbi, H. Y. <strong>Mutation of the E6-AP ubiquitin ligase reduces nuclear inclusion frequency while accelerating polyglutamine-induced pathology in SCA1 mice.</strong> Neuron 24: 879-892, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10624951/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10624951</a>] [<a href="https://doi.org/10.1016/s0896-6273(00)81035-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10624951">Cummings et al. (1999)</a> concluded that nuclear inclusions are not necessary to induce neurodegeneration, but impaired proteasomal degradation of mutant ataxin-1 may contribute to SCA1 pathogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10624951" 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="Davidson, J. D., Riley, B., Burright, E. N., Duvick, L. A., Zoghbi, H. Y., Orr, H. T. <strong>Identification and characterization of an ataxin-1-interactin g protein: A1Up, a ubiquitin-like nuclear protein.</strong> Hum. Molec. Genet. 9: 2305-2312, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11001934/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11001934</a>] [<a href="https://doi.org/10.1093/oxfordjournals.hmg.a018922" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11001934">Davidson et al. (2000)</a> identified an ataxin-1-interacting protein, A1U (<a href="/entry/605440">605440</a>), that localized to the nucleus and cytoplasm of transfected COS-1 cells. A1U contains an N-terminal ubiquitin-like region and has substantial homology to human UBQLN2 (<a href="/entry/300264">300264</a>), a protein that binds the ATPase domain of the HSP70-like Stch protein (<a href="/entry/601100">601100</a>). The authors suggested that A1U may link ataxin-1 with the chaperone and ubiquitin/proteasome pathways, and that ataxin-1 may function in the formation and regulation of multimeric protein complexes within the nucleus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11001934" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using an in vitro RNA-binding assay, <a href="#36" class="mim-tip-reference" title="Yue, S., Serra, H. G., Zoghbi, H. Y., Orr, H. T. <strong>The spinocerebellar ataxia type 1 protein, ataxin-1, has RNA-binding activity that is inversely affected by the length of its polyglutamine tract.</strong> Hum. Molec. Genet. 10: 25-30, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11136710/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11136710</a>] [<a href="https://doi.org/10.1093/hmg/10.1.25" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11136710">Yue et al. (2001)</a> demonstrated that ataxin-1 binds RNA, and that this binding diminishes as the length of its polyglutamine tract increases. The authors suggested that ataxin-1 plays a role in RNA metabolism and that the expansion of the polyglutamine tract may alter this function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11136710" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#22" class="mim-tip-reference" title="Okazawa, H., Rich, T., Chang, A., Lin, X., Waragai, M., Kajikawa, M., Enokido, Y., Komuro, A., Kato, S., Shibata, M., Hatanaka, H., Mouradian, M. M., Sudol, M., Kanazawa, I. <strong>Interaction between mutant ataxin-1 and PQBP-1 affects transcription and cell death.</strong> Neuron 34: 701-713, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12062018/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12062018</a>] [<a href="https://doi.org/10.1016/s0896-6273(02)00697-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12062018">Okazawa et al. (2002)</a> proposed that modified transcription may underlie polyglutamine-mediated pathology and that polyglutamine-binding protein-1 (PQBP1; <a href="/entry/300463">300463</a>) may be involved in the pathology of SCA1. Using in vitro and in vivo assays, they showed that interaction between ataxin-1 and PQBP1 was positively influenced by expanded polyglutamine sequences. In immunoprecipitation experiments, mutant ataxin-1 enhanced interaction between PQBP1 and the RNA polymerase II (pol II) large subunit (<a href="/entry/180660">180660</a>), and the authors proposed that a ternary complex is formed by PQBP1 in the presence of mutant ataxin-1. PQBP1 and mutant ataxin-1 acted cooperatively in cell lines to repress transcription and induce cell death. <a href="#22" class="mim-tip-reference" title="Okazawa, H., Rich, T., Chang, A., Lin, X., Waragai, M., Kajikawa, M., Enokido, Y., Komuro, A., Kato, S., Shibata, M., Hatanaka, H., Mouradian, M. M., Sudol, M., Kanazawa, I. <strong>Interaction between mutant ataxin-1 and PQBP-1 affects transcription and cell death.</strong> Neuron 34: 701-713, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12062018/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12062018</a>] [<a href="https://doi.org/10.1016/s0896-6273(02)00697-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12062018">Okazawa et al. (2002)</a> hypothesized that high expression of PQBP1 in the cerebellum promotes mutant ataxin-1-induced cell death, contributing to the region-specific neurodegeneration seen in SCA1 patient tissues. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12062018" 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 investigate the effect of expanded poly(Q) repeats on ubiquitin/proteasome-dependent proteolysis, <a href="#33" class="mim-tip-reference" title="Verhoef, L. G. G. C., Lindsten, K., Masucci, M. G., Dantuma, N. P. <strong>Aggregate formation inhibits proteasomal degradation of polyglutamine proteins.</strong> Hum. Molec. Genet. 11: 2689-2700, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12374759/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12374759</a>] [<a href="https://doi.org/10.1093/hmg/11.22.2689" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12374759">Verhoef et al. (2002)</a> targeted these proteins for proteasomal degradation by the introduction of an N-end rule degradation signal (i.e., N-terminal arginine residue). While soluble poly(Q) proteins were degraded, they resisted proteasomal degradation once present in the aggregates. Stabilization was also observed for proteins that are co-aggregated via interaction with the expanded poly(Q) domain. Introduction of a degradation signal in ataxin-1/Q92 reduced the incidence of nuclear inclusions and the cellular toxicity, conceivably by accelerating the clearance of the soluble substrate. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12374759" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Chen, H.-K., Fernandez-Funez, P., Acevedo, S. F., Lam, Y. C., Kaytor, M. D., Fernandez, M. H., Aitken, A., Skoulakis, E. M. C., Orr, H. T., Botas, J., Zoghbi, H. Y. <strong>Interaction of Akt-phosphorylated ataxin-1 with 14-3-3 mediates neurodegeneration in spinocerebellar ataxia type 1.</strong> Cell 113: 457-468, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12757707/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12757707</a>] [<a href="https://doi.org/10.1016/s0092-8674(03)00349-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12757707">Chen et al. (2003)</a> discovered that the 14-3-3 protein (see <a href="/entry/113508">113508</a>), a multifunctional regulatory molecule, mediates the neurotoxicity of ataxin-1 by binding and stabilizing it, thereby slowing its normal degradation. The association of ataxin-1 with 14-3-3 was found to be regulated by AKT (<a href="/entry/164730">164730</a>) phosphorylation, and in a Drosophila model of SCA1, both 14-3-3 and Akt modulated neurodegeneration. The authors concluded that their finding that phosphatidylinositol 3-kinase/Akt signaling and 14-3-3 cooperate to modulate the neurotoxicity of ataxin-1 provides insight into SCA1 pathogenesis and identifies potential targets for therapeutic intervention. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12757707" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The pathologic hallmark of neurodegenerative disorders associated with expanded polyglutamine repeats (polyQ) is the cytoplasmic or intranuclear accumulation of polyglutamine inclusions. <a href="#11" class="mim-tip-reference" title="Emamian, E. S., Kaytor, M. D., Duvick, L. A., Zu, T., Tousey, S. K., Zoghbi, H. Y., Clark, H. B., Orr, H. T. <strong>Serine 776 of ataxin-1 is critical for polyglutamine-induced disease in SCA1 transgenic mice.</strong> Neuron 38: 375-387, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12741986/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12741986</a>] [<a href="https://doi.org/10.1016/s0896-6273(03)00258-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12741986">Emamian et al. (2003)</a> noted that the expanded tract may influence the behavior of the host protein and that elements of the protein outside of the polyglutamine tract may influence the course of disease. In vitro, <a href="#11" class="mim-tip-reference" title="Emamian, E. S., Kaytor, M. D., Duvick, L. A., Zu, T., Tousey, S. K., Zoghbi, H. Y., Clark, H. B., Orr, H. T. <strong>Serine 776 of ataxin-1 is critical for polyglutamine-induced disease in SCA1 transgenic mice.</strong> Neuron 38: 375-387, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12741986/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12741986</a>] [<a href="https://doi.org/10.1016/s0896-6273(03)00258-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12741986">Emamian et al. (2003)</a> found that ataxin-1 is phosphorylated at ser776 and that most cells expressing ataxin-1(82Q)-ser776 contained large nuclear inclusions (60%), compared to cells expressing a mutant ataxin-1(82Q)-ala776 (less than 0.1%). Ataxin-1(82Q)-ala776 transgenic mice expressed the protein in Purkinje cell nuclei, but progression and manifestations of disease were substantially reduced. The authors concluded that polyglutamine tract expansion and intranuclear localization are not sufficient to induce disease, and that the ser776 phosphorylation site has a critical role in SCA1 pathogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12741986" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By yeast 2-hybrid analysis, <a href="#13" class="mim-tip-reference" title="Hong, S., Ka, S., Kim, S., Park, Y., Kang, S. <strong>p80 coilin, a coiled body-specific protein, interacts with ataxin-1, the SCA1 gene product.</strong> Biochim. Biophys. Acta 1638: 35-42, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12757932/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12757932</a>] [<a href="https://doi.org/10.1016/s0925-4439(03)00038-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12757932">Hong et al. (2003)</a> found that ataxin-1 interacted with coilin (COIL; <a href="/entry/600272">600272</a>). Mutation analysis indicated that the C-terminal regions of both proteins mediated the interaction. HeLa cells cotransfected with ataxin-1 and coilin showed colocalization of the 2 proteins in aggregates in the nucleoplasm. A mutant form of ataxin-1 containing a polyglutamine expansion also interacted with coilin and localized with some coiled bodies, but it had no effect on their normal nuclear distribution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12757932" 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="#30" class="mim-tip-reference" title="Skinner, P. J., Koshy, B. T., Cummings, C. J., Klement, I. A., Helin, K., Servadio, A., Zoghbi, H. Y., Orr, H. T. <strong>Ataxin-1 with an expanded glutamine tract alters nuclear matrix-associated structures.</strong> Nature 389: 971-974, 1997. Note: Erratum: Nature 39: 307 only, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9353120/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9353120</a>] [<a href="https://doi.org/10.1038/40153" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9353120">Skinner et al. (1997)</a> and <a href="#19" class="mim-tip-reference" title="Matilla, A., Koshy, B. T., Cummings, C. J., Isobe, T., Orr, H. T., Zoghbi, H. Y. <strong>The cerebellar leucine-rich acidic nuclear protein interacts with ataxin-1.</strong> Nature 389: 974-978, 1997. Note: Erratum: Nature 391: 818 only, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9353121/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9353121</a>] [<a href="https://doi.org/10.1038/40159" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9353121">Matilla et al. (1997)</a> showed that, in transfected cells, both wildtype (30 glutamines) and mutant (82 glutamines) Atx1 localized to small dense nuclear bodies. <a href="#32" class="mim-tip-reference" title="Tsai, C.-C., Kao, H.-Y., Mitzutani, A., Banayo, E., Rajan, H., McKeown, M., Evans, R. M. <strong>Ataxin 1, a SCA1 neurodegenerative disorder protein, is functionally linked to the silencing mediator of retinoid and thyroid hormone receptors.</strong> Proc. Nat. Acad. Sci. 101: 4047-4052, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15016912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15016912</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15016912[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/10.1073/pnas.0400615101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15016912">Tsai et al. (2004)</a> demonstrated that Atx1 interacts with the transcriptional corepressor SMRT (silencing mediator for retinoid and thyroid hormone receptors; <a href="/entry/600848">600848</a>) and with histone deacetylase-3 (HDAC3; <a href="/entry/605166">605166</a>). Atx1 binds chromosomes and mediates transcriptional repression when tethered to DNA. Interaction with SMRT-related factors is a conserved feature of Atx1, because Atx1 also binds SMRTER, a Drosophila cognate of SMRT. Significantly, mutant Atx1 forms aggregates in Drosophila, and such mutant Atx1-mediated aggregates sequester SMRTER. Consistently, the neurodegenerative eye phenotype in Drosophila caused by mutant Atx1 was enhanced by a Smrter mutation and, conversely, was suppressed by a chromosomal duplication that contained the wildtype Smrter gene. <a href="#32" class="mim-tip-reference" title="Tsai, C.-C., Kao, H.-Y., Mitzutani, A., Banayo, E., Rajan, H., McKeown, M., Evans, R. M. <strong>Ataxin 1, a SCA1 neurodegenerative disorder protein, is functionally linked to the silencing mediator of retinoid and thyroid hormone receptors.</strong> Proc. Nat. Acad. Sci. 101: 4047-4052, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15016912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15016912</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15016912[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/10.1073/pnas.0400615101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15016912">Tsai et al. (2004)</a> interpreted their results as suggesting that Atx1 is a transcriptional factor whose mutant form exerts its deleterious effects in part by perturbing corepressor-dependent transcriptional pathways. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9353120+9353121+15016912" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By yeast 2-hybrid and mutation analysis, <a href="#21" class="mim-tip-reference" title="Mizutani, A., Wang, L., Rajan, H., Vig, P. J. S., Alaynick, W. A., Thaler, J. P., Tsai, C.-C. <strong>Boat, an AXH domain protein, suppresses the cytotoxicity of mutant ataxin-1.</strong> EMBO J. 24: 3339-3351, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16121196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16121196</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16121196[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/sj.emboj.7600785" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16121196">Mizutani et al. (2005)</a> showed that AXH domain of ATXN1 was required for its interaction with SMRT. Yeast 2-hybrid analysis also showed that ATXN1 interacted with BOAT (ATXN1L), and <a href="#21" class="mim-tip-reference" title="Mizutani, A., Wang, L., Rajan, H., Vig, P. J. S., Alaynick, W. A., Thaler, J. P., Tsai, C.-C. <strong>Boat, an AXH domain protein, suppresses the cytotoxicity of mutant ataxin-1.</strong> EMBO J. 24: 3339-3351, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16121196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16121196</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16121196[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/sj.emboj.7600785" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16121196">Mizutani et al. (2005)</a> confirmed the interaction between BOAT and ATXN1 in human cell culture and Drosophila. Truncation analysis showed that the NBA domain of BOAT mediated its self-association and interaction with ATXN1, whereas the SAR and NBA domains of ATXN1 mediated its self-association and interaction with BOAT. Mutation analysis and reporter gene assays revealed that the AXH domain of ATXN1 was required for transcriptional repression, likely due to its interaction with SMRT. Truncation analysis and reporter gene assays revealed that ATXN1 contains a C-terminal transcriptional repressive domain, whereas BOAT contains independent N- and C-terminal transcriptional repressive domains. Immunoprecipitation analysis showed that endogenous BOAT, SMRT, and ATXN1 interacted in a complex in HeLa cells. Expression of ATXN1 with a polyglutamine expansion (82Q) caused an abnormal eye phenotype in Drosophila, and this phenotype was reversed by coexpression of BOAT. Expression of ATXN1 without the polyglutamine tract (0Q) also caused an abnormal eye phenotype in Drosophila, although it was less severe than that caused by ATXN1(82Q). SCA1 mice, which express human mutant ATXN1 in Purkinje cells, showed reduced expression of both Boat and Smrt compared with wildtype mice. <a href="#21" class="mim-tip-reference" title="Mizutani, A., Wang, L., Rajan, H., Vig, P. J. S., Alaynick, W. A., Thaler, J. P., Tsai, C.-C. <strong>Boat, an AXH domain protein, suppresses the cytotoxicity of mutant ataxin-1.</strong> EMBO J. 24: 3339-3351, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16121196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16121196</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16121196[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/sj.emboj.7600785" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16121196">Mizutani et al. (2005)</a> hypothesized that BOAT inhibits mutant ATXN1 toxicity by dimerizing with ATXN1 and reducing mutant ATXN1 self-association. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16121196" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="Lam, Y. C., Bowman, A. B., Jafar-Nejad, P., Lim, J., Richman, R., Fryer, J. D., Hyun, E. D., Duvick, L. A., Orr, H. T., Botas, J., Zoghbi, H. Y. <strong>ATAXIN-1 interacts with the repressor Capicua in its native complex to cause SCA1 neuropathology.</strong> Cell 127: 1335-1347, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17190598/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17190598</a>] [<a href="https://doi.org/10.1016/j.cell.2006.11.038" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17190598">Lam et al. (2006)</a> examined soluble protein complexes from mouse cerebellum and found that the majority of wildtype and expanded Atxn1 assembles into large stable complexes containing the transcriptional repressor Capicua (Cic; <a href="/entry/612082">612082</a>). Atxn1 directly bound Cic and modulated Cic repressor activity in Drosophila and mammalian cells, and its loss decreased the steady state level of Cic. Interestingly, the S776A mutation, which abrogates the neurotoxicity of expanded Atxn1, substantially reduced the association of mutant Atxn1 with Cic in vivo. <a href="#16" class="mim-tip-reference" title="Lam, Y. C., Bowman, A. B., Jafar-Nejad, P., Lim, J., Richman, R., Fryer, J. D., Hyun, E. D., Duvick, L. A., Orr, H. T., Botas, J., Zoghbi, H. Y. <strong>ATAXIN-1 interacts with the repressor Capicua in its native complex to cause SCA1 neuropathology.</strong> Cell 127: 1335-1347, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17190598/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17190598</a>] [<a href="https://doi.org/10.1016/j.cell.2006.11.038" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17190598">Lam et al. (2006)</a> concluded that their data provided insight into the function of Atxn1 and suggested that the neuropathology of SCA1 (<a href="/entry/164400">164400</a>), caused by expansion of the ATXN1 polyglutamine tract, depends on native, not novel, protein interactions. <a href="#16" class="mim-tip-reference" title="Lam, Y. C., Bowman, A. B., Jafar-Nejad, P., Lim, J., Richman, R., Fryer, J. D., Hyun, E. D., Duvick, L. A., Orr, H. T., Botas, J., Zoghbi, H. Y. <strong>ATAXIN-1 interacts with the repressor Capicua in its native complex to cause SCA1 neuropathology.</strong> Cell 127: 1335-1347, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17190598/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17190598</a>] [<a href="https://doi.org/10.1016/j.cell.2006.11.038" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17190598">Lam et al. (2006)</a> found that the majority of CIC associates with ATXN1 in vivo and that ATXN1 binds CIC through an 8-amino-acid sequence conserved across species. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17190598" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using yeast 2-hybrid screens, coaffinity purification analysis of transfected HEK293 cells, and bioinformatic analysis, <a href="#18" class="mim-tip-reference" title="Lim, J., Hao, T., Shaw, C., Patel, A. J., Szabo, G., Rual, J.-F., Fisk, C. J., Li, N., Smolyar, A., Hill, D. E., Barabasi, A.-L., Vidal, M., Zoghbi, H. Y. <strong>A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration.</strong> Cell 125: 801-814, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16713569/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16713569</a>] [<a href="https://doi.org/10.1016/j.cell.2006.03.032" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16713569">Lim et al. (2006)</a> developed an interaction network for 54 human proteins involved in 23 inherited ataxias. By database analysis, they expanded the core network to include more distantly related interacting proteins that could function as genetic modifiers. A majority (18 of 23) of ataxia-causing proteins interacted either directly or indirectly. ATXN1 showed strong direct interactions with ATXN2 (<a href="/entry/601517">601517</a>) and RBPMS (<a href="/entry/601558">601558</a>), and the N-terminal portion of ATXN1 was required for interaction with RBPMS. RBPMS was a main hub in the network and interacted with many proteins, including 2 cerebellar ataxia-associated proteins, ATN1 (<a href="/entry/607462">607462</a>) and QK1 (<a href="/entry/609590">609590</a>). The ATXN1 interactor COIL also interacted with the ataxia-associated protein puratrophin-1 (PLEKHG4; <a href="/entry/609526">609526</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16713569" 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="#17" class="mim-tip-reference" title="Lim, J., Crespo-Barreto, J., Jafar-Nejad, P., Bowman, A. B., Richman, R., Hill, D. E., Orr, H. T., Zoghbi, H. Y. <strong>Opposing effects of polyglutamine expansion on native protein complexes contribute to SCA1.</strong> Nature 452: 713-718, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18337722/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18337722</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18337722[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature06731" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18337722">Lim et al. (2008)</a> demonstrated that the expanded polyglutamine tract of ATXN1 differentially affects the function of the host protein in the context of different endogenous protein complexes. Polyglutamine expansion in ATXN1 favors the formation of a particular protein complex containing RBM17 (<a href="/entry/606935">606935</a>), contributing to SCA1 neuropathology by means of a gain-of-function mechanism. Concomitantly, polyglutamine expansion attenuates the formation and function of another protein complex containing ATXN1 and capicua, contributing to SCA1 through a partial loss-of-function mechanism. <a href="#17" class="mim-tip-reference" title="Lim, J., Crespo-Barreto, J., Jafar-Nejad, P., Bowman, A. B., Richman, R., Hill, D. E., Orr, H. T., Zoghbi, H. Y. <strong>Opposing effects of polyglutamine expansion on native protein complexes contribute to SCA1.</strong> Nature 452: 713-718, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18337722/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18337722</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18337722[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature06731" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18337722">Lim et al. (2008)</a> concluded that their model provides mechanistic insight into the molecular pathogenesis of SCA1 as well as other polyglutamine diseases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18337722" 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>Notch signaling involves proteolytic release of the Notch intracellular domain (NICD), followed by NICD-dependent gene activation. <a href="#31" class="mim-tip-reference" title="Tong, X., Gui, H., Jin, F., Heck, B. W., Lin, P., Ma, J., Fondell, J. D., Tsai, C.-C. <strong>Ataxin-1 and brother of ataxin-1 are components of the Notch signalling pathway.</strong> EMBO Rep. 12: 428-435, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21475249/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21475249</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21475249[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/embor.2011.49" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21475249">Tong et al. (2011)</a> found that expression of human BOAT1 in Drosophila wing disrupted Notch signaling, leading to wing defects. Coimmunoprecipitation analysis of HEK293 cells revealed that both BOAT1 and ATXN1 precipitated CBF1 (RBPJ; <a href="/entry/147183">147183</a>), which functions as a transcriptional activator when associated with NICD. Protein pull-down and yeast 2-hybrid analyses confirmed the interactions and showed that BOAT1 and ATXN1 competed for CBF1 binding. Coimmunoprecipitation experiments showed that NICD disrupted CBF1-BOAT/ATXN1 interactions. Reporter gene assays revealed that both BOAT1 and ATXN1 inhibited CBF1 activity at the HEY1 (<a href="/entry/602953">602953</a>) promoter. Chromatin immunoprecipitation assays showed that Boat1 and Atxn1, in addition to Smrt, occupied the Hey1 promoter in differentiating mouse C2C12 myoblasts. Atxn1 bound the Hey1 promoter transiently, whereas Boat1 and Smrt remained bound to the Hey1 promoter under the same conditions. <a href="#31" class="mim-tip-reference" title="Tong, X., Gui, H., Jin, F., Heck, B. W., Lin, P., Ma, J., Fondell, J. D., Tsai, C.-C. <strong>Ataxin-1 and brother of ataxin-1 are components of the Notch signalling pathway.</strong> EMBO Rep. 12: 428-435, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21475249/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21475249</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21475249[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/embor.2011.49" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21475249">Tong et al. (2011)</a> concluded that BOAT1 and ATXN1 are chromatin-binding factors that repress Notch signaling in the absence of NCID by acting as CBF1 corepressors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21475249" 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>Alternative ATXN1</em></strong></p><p>
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Using coimmunoprecipitation and protein pull-down assays, <a href="#3" class="mim-tip-reference" title="Bergeron, D., Lapointe, C., Bissonnette, C., Tremblay, G., Motard, J., Roucou, X. <strong>An out-of-frame overlapping reading frame in the ataxin-1 coding sequence encodes a novel ataxin-1 interacting protein.</strong> J. Biol. Chem. 288: 21824-21835, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23760502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23760502</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23760502[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/10.1074/jbc.M113.472654" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23760502">Bergeron et al. (2013)</a> found that ALT-ATXN1 interacted directly with ATXN1. Deletion analysis revealed that ALT-ATXN1 interacted with an N-terminal domain of ATXN1 and not with the polyglutamine track. Neither ATXN1 nor ALT-ATXN1 directly affected expression or solubility of the other protein, and ALT-ATXN1 translation was independent of the number of CAG repeats in the transcript. ATXN1 spontaneously formed intranuclear inclusion in the absence of ALT-ATXN1 and recruited ALT-ATXN1 to these inclusions. ALT-ATXN1 also bound to poly(A) RNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23760502" 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><strong><em>ATXN1 Polyglutamine Expansion in SCA1</em></strong></p><p>
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<a href="#24" class="mim-tip-reference" title="Orr, H. T., Chung, M., Banfi, S., Kwiatkowski, T. J., Jr., Servadio, A., Beaudet, A. L., McCall, A. E., Duvick, L. A., Ranum, L. P. W., Zoghbi, H. Y. <strong>Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1.</strong> Nature Genet. 4: 221-226, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8358429/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8358429</a>] [<a href="https://doi.org/10.1038/ng0793-221" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8358429">Orr et al. (1993)</a> demonstrated that the basic defect in spinocerebellar ataxia-1 (<a href="/entry/164400">164400</a>) consists of expansion of a trinucleotide CAG repeat (<a href="#0001">601556.0001</a>) and <a href="#1" class="mim-tip-reference" title="Banfi, S., Servadio, A., Chung, M., Kwiatkowski, T. J., Jr., McCall, A. E., Duvick, L. A., Shen, Y., Roth, E. J., Orr, H. T., Zoghbi, H. Y. <strong>Identification and characterization of the gene causing type 1 spinocerebellar ataxia.</strong> Nature Genet. 7: 513-520, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7951322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7951322</a>] [<a href="https://doi.org/10.1038/ng0894-513" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7951322">Banfi et al. (1994)</a> identified the gene as ataxin-1. Both groups showed that the repeat is present not only in genomic DNA but also in a 10-kb mRNA transcript. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7951322+8358429" 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="#29" class="mim-tip-reference" title="Sisodia, S. S. <strong>Nuclear inclusions in glutamine repeat disorders: are they pernicious, coincidental, or beneficial?</strong> Cell 95: 1-4, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9778239/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9778239</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81743-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9778239">Sisodia (1998)</a> reviewed the significance of nuclear inclusions in glutamine repeat disorders. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9778239" 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="#25" class="mim-tip-reference" title="Orr, H. T., Zoghbi, H. Y. <strong>SCA1 molecular genetics: a history of a 13 year collaboration against glutamines.</strong> Hum. Molec. Genet. 10: 2307-2311, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11673415/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11673415</a>] [<a href="https://doi.org/10.1093/hmg/10.20.2307" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11673415">Orr and Zoghbi (2001)</a> reviewed the history of unraveling the molecular pathogenesis of SCA1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11673415" 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>Genetic Anticipation</em></strong></p><p>
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<a href="#6" class="mim-tip-reference" title="Chung, M., Ranum, L. P. W., Duvick, L. A., Servadio, A., Zoghbi, H. Y., Orr, H. T. <strong>Evidence for a mechanism predisposing to intergenerational CAG repeat instability in spinocerebellar ataxia type 1.</strong> Nature Genet. 5: 254-258, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8275090/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8275090</a>] [<a href="https://doi.org/10.1038/ng1193-254" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8275090">Chung et al. (1993)</a> found that 63% of paternal transmissions of the mutant allele show an increase in repeat number, whereas 69% of maternal transmissions show no change or a decrease in repeat number. Sequence analysis showed that 98% of unexpanded alleles had an interrupted repeat configuration, whereas a contiguous repeat (CAG)n was found in expanded alleles. This indicated that the repeat instability in ATXN1 is more complex than a simple variation in repeat number and that the loss of an interruption predisposes the ATXN1 (CAG)n to expansion. <a href="#20" class="mim-tip-reference" title="Matilla, T., Volpini, V., Genis, D., Rosell, J., Corral, J., Davalos, A., Molins, A., Estivill, X. <strong>Presymptomatic analysis of spinocerebellar ataxia type 1 (SCA1) via the expansion of the SCA1 CAG-repeat in a large pedigree displaying anticipation and parental male bias.</strong> Hum. Molec. Genet. 2: 2123-2128, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8111382/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8111382</a>] [<a href="https://doi.org/10.1093/hmg/2.12.2123" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8111382">Matilla et al. (1993)</a> studied the expansion of the ATXN1 gene CAG repeat in a large family in which spinocerebellar ataxia showed the phenomenon of anticipation. There were 41 affected members with no juvenile cases of SCA1, the mean age of onset being 36 years. The family also showed the phenomenon of parental male bias; i.e., the age of onset was younger and the duration of illness before death was shorter in the members of the family who inherited the disorder from the father. In this large Spanish kindred, <a href="#20" class="mim-tip-reference" title="Matilla, T., Volpini, V., Genis, D., Rosell, J., Corral, J., Davalos, A., Molins, A., Estivill, X. <strong>Presymptomatic analysis of spinocerebellar ataxia type 1 (SCA1) via the expansion of the SCA1 CAG-repeat in a large pedigree displaying anticipation and parental male bias.</strong> Hum. Molec. Genet. 2: 2123-2128, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8111382/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8111382</a>] [<a href="https://doi.org/10.1093/hmg/2.12.2123" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8111382">Matilla et al. (1993)</a> found 9 clinically unaffected persons between ages 18 and 40 years who had expansions of the CAG repeat within the pathogenetic range. In 22 other genetically 'at risk' individuals, they found that the number of (CAG)n repeats in the ATXN1 gene was within the normal range. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8111382+8275090" 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="Jodice, C., Malaspina, P., Persichetti, F., Novelletto, A., Spadaro, M., Giunti, P., Morocutti, C., Terrenato, L., Harding, A. E., Frontali, M. <strong>Effect of trinucleotide repeat length and parental sex on phenotypic variation in spinocerebellar ataxia 1.</strong> Am. J. Hum. Genet. 54: 959-965, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8198139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8198139</a>]" pmid="8198139">Jodice et al. (1994)</a> found trinucleotide repeat expansion in 64 subjects from 19 families: 57 patients with SCA1 and 7 subjects predicted, by haplotype analysis, to carry the mutation. Comparison with a large set of normal chromosomes showed 2 distinct distributions with a much wider variation among expanded chromosomes. The sex of the transmitting parent played a major role in the size distribution of expanded alleles, those with more than 54 repeats being transmitted by affected fathers exclusively. Alleles with 46 to 54 repeats were transmitted by affected fathers and mothers in equal proportions. On the other hand, the sex ratio of offspring receiving either more than 54 or less than 54 repeats approached the expected 50:50. If a steady-state distribution of repeat numbers is assumed to persist through the generations, this raises the question as to why affected females transmitting alleles with more than 54 repeats are lacking, while females receiving more than 54 repeats exist. This may be explained, at least in part, by reduced biologic fitness. Detailed clinical follow-up of a subset of patients by <a href="#14" class="mim-tip-reference" title="Jodice, C., Malaspina, P., Persichetti, F., Novelletto, A., Spadaro, M., Giunti, P., Morocutti, C., Terrenato, L., Harding, A. E., Frontali, M. <strong>Effect of trinucleotide repeat length and parental sex on phenotypic variation in spinocerebellar ataxia 1.</strong> Am. J. Hum. Genet. 54: 959-965, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8198139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8198139</a>]" pmid="8198139">Jodice et al. (1994)</a> demonstrated significant relationships between increasing repeat number on expanded chromosomes and earlier age at onset, faster progression of the disease, and earlier age at death. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8198139" 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>Association with Schizophrenia</em></strong></p><p>
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For discussion of a possible association between the ATXN1 CAG repeat and risk of schizophrenia, see SCZD3 (<a href="/entry/600511">600511</a>).</p>
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<p>In order to determine how the human ATXN1 gene acquired the CAG repeat structure with interruptions, <a href="#15" class="mim-tip-reference" title="Kurosaki, T., Ninokata, A., Wang, L., Ueda, S. <strong>Evolutionary scenario for acquisition of CAG repeats in human SCA1 gene.</strong> Gene 373: 23-27, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16497448/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16497448</a>] [<a href="https://doi.org/10.1016/j.gene.2005.12.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16497448">Kurosaki et al. (2006)</a> analyzed the Atxn1 gene in many primate species, rat, and mouse. They found no repeats in the corresponding region of rodent, prosimian, and New World monkey Atxn1 genes. They found perfect uninterrupted CAG repeats in Old World monkeys and interrupted CAG repeats in hominoids. <a href="#15" class="mim-tip-reference" title="Kurosaki, T., Ninokata, A., Wang, L., Ueda, S. <strong>Evolutionary scenario for acquisition of CAG repeats in human SCA1 gene.</strong> Gene 373: 23-27, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16497448/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16497448</a>] [<a href="https://doi.org/10.1016/j.gene.2005.12.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16497448">Kurosaki et al. (2006)</a> concluded that there was no repetitive CAG structure in the common ancestor of primates and that the interrupted repetitive structure of the human ATXN1 gene was gradually acquired during evolution of the simian lineage. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16497448" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#2" class="mim-tip-reference" title="Banfi, S., Servadio, A., Chung, M.-y., Capozzoli, F., Duvick, L. A., Elde, R., Zoghbi, H. Y., Orr, H. T. <strong>Cloning and developmental expression analysis of the murine homolog of the spinocerebellar ataxia type 1 gene (Sca1).</strong> Hum. Molec. Genet. 5: 33-40, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8789437/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8789437</a>] [<a href="https://doi.org/10.1093/hmg/5.1.33" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8789437">Banfi et al. (1996)</a> found that murine Sca1 and human ataxin-1 are highly homologous but the CAG repeat is virtually absent in the mouse sequence, suggesting that the polyglutamine stretch is not essential for the normal function of ataxin-1 in mice. Cellular and developmental expression of the murine homolog was examined using RNA in situ hybridization. During cerebellar development, there is a transient burst of Sca1 expression at postnatal day 14, when the murine cerebellar cortex becomes physiologically functional. There was also marked expression of Sca1 in mesenchymal cells of the intervertebral discs during development of the spinal column. The results suggested to the authors that the normal Sca1 gene has a role at specific stages of both cerebellar and vertebral column development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8789437" 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>PQBP1 (<a href="/entry/300463">300463</a>) is a polyglutamine-binding nuclear protein which has been shown to interact with ataxin-1. <a href="#23" class="mim-tip-reference" title="Okuda, T., Hattori, H., Takeuchi, S., Shimizu, J., Ueda, H., Palvimo, J. J., Kanazawa, I., Kawano, H., Nakagawa, M., Okazawa, H. <strong>PQBP-1 transgenic mice show a late-onset motor neuron disease-like phenotype.</strong> Hum. Molec. Genet. 12: 711-725, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12651867/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12651867</a>] [<a href="https://doi.org/10.1093/hmg/ddg084" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12651867">Okuda et al. (2003)</a> generated transgenic mice overexpressing human PQBP1. The mice showed a late-onset and gradually progressive motor neuron disease-like phenotype suggestive of the neurogenic muscular atrophy observed in SCA1 patients. Ataxia could not be discriminated from predominant progressive weakness. Pathologic examinations of the transgenic mice revealed loss of Purkinje and granular cells in the cerebellum as well as loss of motor neurons in the spinal anterior horn, corresponding to the pathology of human SCA1. <a href="#23" class="mim-tip-reference" title="Okuda, T., Hattori, H., Takeuchi, S., Shimizu, J., Ueda, H., Palvimo, J. J., Kanazawa, I., Kawano, H., Nakagawa, M., Okazawa, H. <strong>PQBP-1 transgenic mice show a late-onset motor neuron disease-like phenotype.</strong> Hum. Molec. Genet. 12: 711-725, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12651867/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12651867</a>] [<a href="https://doi.org/10.1093/hmg/ddg084" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12651867">Okuda et al. (2003)</a> concluded that excessive action of PQBP1 causes neuronal dysfunction and that PQBP1 may be involved in the pathology of SCA1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12651867" 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="#35" class="mim-tip-reference" title="Watase, K., Venken, K. J. T., Sun, Y., Orr, H. T., Zoghbi, H. Y. <strong>Regional differences of somatic CAG repeat instability do not account for selective neuronal vulnerability in a knock-in mouse model of SCA1.</strong> Hum. Molec. Genet. 12: 2789-2795, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12952864/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12952864</a>] [<a href="https://doi.org/10.1093/hmg/ddg300" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12952864">Watase et al. (2003)</a> investigated the pattern of CAG repeat instability in a knockin mouse model of SCA1. Small pool (SP)-PCR analysis on DNA from various neuronal and nonneuronal tissues revealed that somatic repeat instability was highest in the striatum. In the 2 SCA1-vulnerable tissues, cerebellum and spinal cord, there were substantial differences in the profile of mosaicism. <a href="#35" class="mim-tip-reference" title="Watase, K., Venken, K. J. T., Sun, Y., Orr, H. T., Zoghbi, H. Y. <strong>Regional differences of somatic CAG repeat instability do not account for selective neuronal vulnerability in a knock-in mouse model of SCA1.</strong> Hum. Molec. Genet. 12: 2789-2795, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12952864/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12952864</a>] [<a href="https://doi.org/10.1093/hmg/ddg300" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12952864">Watase et al. (2003)</a> suggested that in SCA1 there is no clear causal relationship between the degree of somatic instability and selective neuronal vulnerability. The finding that somatic instability is most pronounced in the striatum of various knockin models of polyglutamine diseases may suggest a role of trans-acting tissue- or cell-specific factors in mediating the instability. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12952864" 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="#26" class="mim-tip-reference" title="Serra, H. G., Byam, C. E., Lande, J. D., Tousey, S. K., Zoghbi, H. Y., Orr, H. T. <strong>Gene profiling links SCA1 pathophysiology to glutamate signaling in Purkinje cells of transgenic mice.</strong> Hum. Molec. Genet. 13: 2535-2543, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15317756/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15317756</a>] [<a href="https://doi.org/10.1093/hmg/ddh268" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15317756">Serra et al. (2004)</a> used DNA microarrays to determine the pattern of gene expression in SCA1 transgenic mice at 5 weeks (prior to onset of pathology) and at 12 weeks (midpoint of disease progression). By comparing the pattern of gene expression in the SCA1 ataxic B05-ataxin-1(82Q) transgenic mouse line with those seen in 2 nonataxic lines, A02-ataxin-1(30Q) and K772T(82Q), 9 genes were identified whose expression was consistently altered in the cerebellum of B05(82Q) mice at 5 and 12 weeks of age. Five of the genes formed a biologic cohort centered on glutamate signaling pathways in Purkinje cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15317756" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using a conditional transgenic mouse model of SCA1, <a href="#27" class="mim-tip-reference" title="Serra, H. G., Duvick, L., Zu, T., Carlson, K., Stevens, S., Jorgensen, N., Lysholm, A., Burright, E., Zoghbi, H. Y., Clark, H. B., Andresen, J. M., Orr, H. T. <strong>ROR-alpha-mediated Purkinje cell development determines disease severity in adult SCA1 mice.</strong> Cell 127: 697-708, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17110330/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17110330</a>] [<a href="https://doi.org/10.1016/j.cell.2006.09.036" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17110330">Serra et al. (2006)</a> showed that delaying postnatal expression of mutant human ATXN1 until completion of cerebellar maturation led to a substantial reduction in disease severity in adults compared with early postnatal expression of mutant ATXN1. Microarray analysis revealed that genes regulated by Rora (<a href="/entry/600825">600825</a>), a transcription factor critical for cerebellar development, were downregulated at an early stage of disease in Purkinje cells of SCA1 transgenic mice. Rora mRNA and protein levels were reduced in Purkinje cells of SCA1 transgenic mice, and the effect of mutant ATXN1 on Rora protein levels appeared to be independent of its effect on Rora mRNA levels. Partial loss of Rora enhanced the pathogenicity of mutant ATXN1 in transgenic mice. Coimmunoprecipitation and pull-down analyses suggested the existence of a complex containing Atxn1, Rora, and the Rora coactivator Tip60 (HTATIP; <a href="/entry/601409">601409</a>), with Atxn1 and Tip60 interacting directly. <a href="#27" class="mim-tip-reference" title="Serra, H. G., Duvick, L., Zu, T., Carlson, K., Stevens, S., Jorgensen, N., Lysholm, A., Burright, E., Zoghbi, H. Y., Clark, H. B., Andresen, J. M., Orr, H. T. <strong>ROR-alpha-mediated Purkinje cell development determines disease severity in adult SCA1 mice.</strong> Cell 127: 697-708, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17110330/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17110330</a>] [<a href="https://doi.org/10.1016/j.cell.2006.09.036" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17110330">Serra et al. (2006)</a> concluded that RORA and TIP60 have a role in SCA1 and proposed that their findings provide a mechanism by which compromised cerebellar development contributes to the severity of neurodegeneration in an adult. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17110330" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="Lam, Y. C., Bowman, A. B., Jafar-Nejad, P., Lim, J., Richman, R., Fryer, J. D., Hyun, E. D., Duvick, L. A., Orr, H. T., Botas, J., Zoghbi, H. Y. <strong>ATAXIN-1 interacts with the repressor Capicua in its native complex to cause SCA1 neuropathology.</strong> Cell 127: 1335-1347, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17190598/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17190598</a>] [<a href="https://doi.org/10.1016/j.cell.2006.11.038" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17190598">Lam et al. (2006)</a> determined that wildtype and polyglutamine-expanded Atxn1 associate into a group of large protein complexes containing the transcriptional repressor Capicua (CIC; <a href="/entry/612082">612082</a>) in mouse cerebellum and differentially modify CIC activity. However, although specific interactions had been clearly implicated in neurotoxicity, it was unclear whether the neurotoxicity of the mutant protein occurred in its native state by association into normal endogenous protein complexes or by the aberrant interactions and new complexes formed by the misfolding or aggregating Atxn1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17190598" 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>Studies of the pathogenesis of SCA1 supported a model in which the expanded glutamine tract in the ATXN1 gene causes toxicity by modulating the normal activities of that gene. To explore native interactions that modify the toxicity of ATXN1, <a href="#4" class="mim-tip-reference" title="Bowman, A. B., Lam, Y. C., Jafar-Nejad, P., Chen, H.-K., Richman, R., Samaco, R. C., Fryer, J. D., Kahle, J. J., Orr, H. T., Zoghbi, H. Y. <strong>Duplication of Atxn1l suppresses SCA1 neuropathology by decreasing incorporation of polyglutamine-expanded ataxin-1 into native complexes.</strong> Nature Genet. 39: 373-379, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17322884/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17322884</a>] [<a href="https://doi.org/10.1038/ng1977" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17322884">Bowman et al. (2007)</a> generated a targeted duplication of mouse Ataxn1l and tested the role of this protein in SCA1 pathology. Using a knockin mouse model of SCA1 that recapitulates the selective neurodegeneration seen in affected individuals, <a href="#4" class="mim-tip-reference" title="Bowman, A. B., Lam, Y. C., Jafar-Nejad, P., Chen, H.-K., Richman, R., Samaco, R. C., Fryer, J. D., Kahle, J. J., Orr, H. T., Zoghbi, H. Y. <strong>Duplication of Atxn1l suppresses SCA1 neuropathology by decreasing incorporation of polyglutamine-expanded ataxin-1 into native complexes.</strong> Nature Genet. 39: 373-379, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17322884/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17322884</a>] [<a href="https://doi.org/10.1038/ng1977" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17322884">Bowman et al. (2007)</a> found that elevated Atxn1l levels suppress neuropathology by displacing mutant Atxn1 from its native complex with Capicua. The results provided genetic evidence that the selective neuropathology of SCA1 arises from modulation of a core functional activity of ATXN1, and they underscored the importance of studying the paralogs of genes mutated in neurodegenerative diseases to gain insight into mechanisms of pathogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17322884" 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="Duvick, L., Barnes, J., Ebner, B., Agrawal, S., Andresen, M., Lim, J., Giesler, G. J., Zoghbi, H. Y., Orr, H. T. <strong>SCA1-like disease in mice expressing wild-type ataxin-1 with a serine to aspartic acid replacement at residue 776.</strong> Neuron 67: 929-935, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20869591/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20869591</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20869591[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.2010.08.022" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20869591">Duvick et al. (2010)</a> observed that transgenic Atxn1 mice with a wildtype glutamine tract (30Q) and expression of a ser776-to-asp (S776D) phosphogenic substitution developed pathologic changes in cerebellar Purkinje cells, such as dendritic atrophy and decreased arborization of climbing fibers, that resembled those of mice carrying only an expanded polyglutamine tract (82Q). D776/30Q mice also showed progressive motor dysfunction, similar to S776/82Q mice. However, the D776/30Q genotype did not induce cell death. The study showed that a single amino acid substitution outside of the polyQ tract converted wildtype Atxn1 into a toxic protein with the pathogenic capabilities of the protein with an expanded polyQ tract. Moreover, the D776 substitution enhanced the pathogenicity of Atxn1(82Q). The results supported a model in which disease pathogenesis involves changes in regions of the protein in addition to the polyglutamine tract. Alteration at ser776 was critical for neuronal dysfunction, but an expanded polyglutamine tract was necessary for neuronal death. <a href="#9" class="mim-tip-reference" title="Duvick, L., Barnes, J., Ebner, B., Agrawal, S., Andresen, M., Lim, J., Giesler, G. J., Zoghbi, H. Y., Orr, H. T. <strong>SCA1-like disease in mice expressing wild-type ataxin-1 with a serine to aspartic acid replacement at residue 776.</strong> Neuron 67: 929-935, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20869591/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20869591</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20869591[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.2010.08.022" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20869591">Duvick et al. (2010)</a> concluded that disease initiation and late-stage induction of neuronal death are distinct disease phases, and suggested that inhibiting phosphorylation may be a therapeutic strategy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20869591" 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 determine the long-term effects of exercise, <a href="#12" class="mim-tip-reference" title="Fryer, J. D., Yu, P., Kang, H., Mandel-Brehm, C., Carter, A. N., Crespo-Barreto, J., Gao, V., Flora, A., Shaw, C., Orr, H. T., Zoghbi, H. Y. <strong>Exercise and genetic rescue of SCA1 via the transcriptional repressor Capicua.</strong> Science 334: 690-693, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22053053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22053053</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22053053[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1212673" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22053053">Fryer et al. (2011)</a> implemented a mild exercise regimen in a mouse model of SCA1 and found a considerable improvement in survival accompanied by upregulation of epidermal growth factor and consequential downregulation of Capicua, which is an ATXN1 interactor. Offspring of Capicua mutant mice bred to Sca1 mice showed significant improvement of all disease phenotypes. Although polyglutamine-expanded Atxn1 caused some loss of Capicua function, further reduction of Capicua levels--either genetically or by exercise--mitigated the disease phenotypes by dampening the toxic gain of function. <a href="#12" class="mim-tip-reference" title="Fryer, J. D., Yu, P., Kang, H., Mandel-Brehm, C., Carter, A. N., Crespo-Barreto, J., Gao, V., Flora, A., Shaw, C., Orr, H. T., Zoghbi, H. Y. <strong>Exercise and genetic rescue of SCA1 via the transcriptional repressor Capicua.</strong> Science 334: 690-693, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22053053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22053053</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22053053[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1212673" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22053053">Fryer et al. (2011)</a> concluded that exercise might have long-term beneficial effects in other ataxias and neurodegenerative diseases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22053053" 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="#10" class="mim-tip-reference" title="Edamakanti, C. R., Do, J., Didonna, A., Martina, M., Opal, P. <strong>Mutant ataxin1 disrupts cerebellar development in spinocerebellar ataxia type 1.</strong> J. Clin. Invest. 128: 2252-2265, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29533923/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29533923</a>] [<a href="https://doi.org/10.1172/JCI96765" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29533923">Edamakanti et al. (2018)</a> studied SCA1 knockin mice in which one allele expressed Atxn1 with a pathogenic polyglutamine expansion and the other allele expressed normal mouse Atxn1. Knockin mice showed increased proliferation of postnatal cerebellar stem cells. These hyperproliferating stem cells tended to differentiate into GABAergic interneurons rather than astrocytes, which gave rise to a greater number of basket cells and stellate cells than Purkinje neurons. Cultures of cerebellar stem cells from knockin mice showed increased proliferation and differentiation in vitro, consistent with the in vivo analysis. The altered stem-cell phenotype in knockin mice appeared to be caused by a cell-autonomous gain of Atxn1 function within the cerebellar stem cells themselves. The authors also showed that more GABAergic synapses in the cerebella of knockin mice resulted in increased inhibitory synaptic connections to Purkinje neurons and disrupted cerebellar Purkinje cell function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29533923" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=601556[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<strong>.0001 SPINOCEREBELLAR ATAXIA 1</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs193922926 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs193922926;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs193922926" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs193922926" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>The cause of spinocerebellar ataxia-1 (SCA1; <a href="/entry/164400">164400</a>) is an expansion of a (CAG)n repeat in the gene encoding ataxin-1 located on 6p (<a href="#24" class="mim-tip-reference" title="Orr, H. T., Chung, M., Banfi, S., Kwiatkowski, T. J., Jr., Servadio, A., Beaudet, A. L., McCall, A. E., Duvick, L. A., Ranum, L. P. W., Zoghbi, H. Y. <strong>Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1.</strong> Nature Genet. 4: 221-226, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8358429/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8358429</a>] [<a href="https://doi.org/10.1038/ng0793-221" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8358429">Orr et al., 1993</a>; <a href="#1" class="mim-tip-reference" title="Banfi, S., Servadio, A., Chung, M., Kwiatkowski, T. J., Jr., McCall, A. E., Duvick, L. A., Shen, Y., Roth, E. J., Orr, H. T., Zoghbi, H. Y. <strong>Identification and characterization of the gene causing type 1 spinocerebellar ataxia.</strong> Nature Genet. 7: 513-520, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7951322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7951322</a>] [<a href="https://doi.org/10.1038/ng0894-513" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7951322">Banfi et al., 1994</a>). Most unexpanded alleles have an interrupted repeat configuration, whereas a contiguous repeat (CAG)n is found in expanded alleles. The repeat instability in ATXN1 is probably more complex than a simple variation in repeat number; the loss of an interruption predisposes the ATXN1 (CAG)n repeat to expansion. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7951322+8358429" 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="#37" class="mim-tip-reference" title="Zuhlke, C., Dalski, A., Hellenbroich, Y., Bubel, S., Schwinger, E., Burk, K. <strong>Spinocerebellar ataxia type 1 (SCA1): Phenotype-genotype correlation studies in intermediate alleles.</strong> Europ. J. Hum. Genet. 10: 204-209, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11973625/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11973625</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200788" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11973625">Zuhlke et al. (2002)</a> analyzed the CAG repeat length and composition in the ATXN1 gene in 16 individuals with alleles ranging from 36 to 43 triplets. Alleles with 36 to 38 triplets were present in individuals with ataxia but without additional characteristic features of SCA1. SCA1 phenotypes were found for patients with 41 and 43 triplets. The 39 triplet allele missing CAT interruptions was associated with symptoms characteristic for SCA1 in 4 patients, whereas the interrupted allele with 39 triplets did not cause characteristic SCA1 features in 1 individual. These findings suggested a change from normal to pathologic alleles at 39 triplets depending on the presence of CAT interruptions in the CAG repeat. Stable inheritance of the uninterrupted 39 triplet allele was observed in 1 familial case of SCA1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11973625" 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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Banfi, S., Servadio, A., Chung, M., Kwiatkowski, T. J., Jr., McCall, A. E., Duvick, L. A., Shen, Y., Roth, E. J., Orr, H. T., Zoghbi, H. Y.
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<strong>Identification and characterization of the gene causing type 1 spinocerebellar ataxia.</strong>
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Nature Genet. 7: 513-520, 1994.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7951322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7951322</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7951322" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng0894-513" target="_blank">Full Text</a>]
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Banfi, S., Servadio, A., Chung, M.-y., Capozzoli, F., Duvick, L. A., Elde, R., Zoghbi, H. Y., Orr, H. T.
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<strong>Cloning and developmental expression analysis of the murine homolog of the spinocerebellar ataxia type 1 gene (Sca1).</strong>
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Hum. Molec. Genet. 5: 33-40, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8789437/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8789437</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8789437" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Bergeron, D., Lapointe, C., Bissonnette, C., Tremblay, G., Motard, J., Roucou, X.
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<strong>An out-of-frame overlapping reading frame in the ataxin-1 coding sequence encodes a novel ataxin-1 interacting protein.</strong>
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J. Biol. Chem. 288: 21824-21835, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23760502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23760502</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23760502[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=23760502" 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.M113.472654" target="_blank">Full Text</a>]
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|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Bowman2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bowman, A. B., Lam, Y. C., Jafar-Nejad, P., Chen, H.-K., Richman, R., Samaco, R. C., Fryer, J. D., Kahle, J. J., Orr, H. T., Zoghbi, H. Y.
|
|
<strong>Duplication of Atxn1l suppresses SCA1 neuropathology by decreasing incorporation of polyglutamine-expanded ataxin-1 into native complexes.</strong>
|
|
Nature Genet. 39: 373-379, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17322884/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17322884</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17322884" 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/ng1977" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Chen2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chen, H.-K., Fernandez-Funez, P., Acevedo, S. F., Lam, Y. C., Kaytor, M. D., Fernandez, M. H., Aitken, A., Skoulakis, E. M. C., Orr, H. T., Botas, J., Zoghbi, H. Y.
|
|
<strong>Interaction of Akt-phosphorylated ataxin-1 with 14-3-3 mediates neurodegeneration in spinocerebellar ataxia type 1.</strong>
|
|
Cell 113: 457-468, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12757707/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12757707</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12757707" 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/s0092-8674(03)00349-0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Chung1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chung, M., Ranum, L. P. W., Duvick, L. A., Servadio, A., Zoghbi, H. Y., Orr, H. T.
|
|
<strong>Evidence for a mechanism predisposing to intergenerational CAG repeat instability in spinocerebellar ataxia type 1.</strong>
|
|
Nature Genet. 5: 254-258, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8275090/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8275090</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8275090" 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/ng1193-254" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Cummings1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cummings, C. J., Reinstein, E., Sun, Y., Antalffy, B., Jiang, Y., Ciechanover, A., Orr, H. T., Beaudet, A. L., Zoghbi, H. Y.
|
|
<strong>Mutation of the E6-AP ubiquitin ligase reduces nuclear inclusion frequency while accelerating polyglutamine-induced pathology in SCA1 mice.</strong>
|
|
Neuron 24: 879-892, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10624951/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10624951</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10624951" 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(00)81035-1" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Davidson2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Davidson, J. D., Riley, B., Burright, E. N., Duvick, L. A., Zoghbi, H. Y., Orr, H. T.
|
|
<strong>Identification and characterization of an ataxin-1-interactin g protein: A1Up, a ubiquitin-like nuclear protein.</strong>
|
|
Hum. Molec. Genet. 9: 2305-2312, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11001934/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11001934</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11001934" 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/oxfordjournals.hmg.a018922" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Duvick2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Duvick, L., Barnes, J., Ebner, B., Agrawal, S., Andresen, M., Lim, J., Giesler, G. J., Zoghbi, H. Y., Orr, H. T.
|
|
<strong>SCA1-like disease in mice expressing wild-type ataxin-1 with a serine to aspartic acid replacement at residue 776.</strong>
|
|
Neuron 67: 929-935, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20869591/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20869591</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20869591[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=20869591" 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/j.neuron.2010.08.022" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Edamakanti2018" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Edamakanti, C. R., Do, J., Didonna, A., Martina, M., Opal, P.
|
|
<strong>Mutant ataxin1 disrupts cerebellar development in spinocerebellar ataxia type 1.</strong>
|
|
J. Clin. Invest. 128: 2252-2265, 2018.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29533923/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29533923</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29533923" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI96765" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Emamian2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Emamian, E. S., Kaytor, M. D., Duvick, L. A., Zu, T., Tousey, S. K., Zoghbi, H. Y., Clark, H. B., Orr, H. T.
|
|
<strong>Serine 776 of ataxin-1 is critical for polyglutamine-induced disease in SCA1 transgenic mice.</strong>
|
|
Neuron 38: 375-387, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12741986/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12741986</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12741986" 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(03)00258-7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Fryer2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fryer, J. D., Yu, P., Kang, H., Mandel-Brehm, C., Carter, A. N., Crespo-Barreto, J., Gao, V., Flora, A., Shaw, C., Orr, H. T., Zoghbi, H. Y.
|
|
<strong>Exercise and genetic rescue of SCA1 via the transcriptional repressor Capicua.</strong>
|
|
Science 334: 690-693, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22053053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22053053</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22053053[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=22053053" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1212673" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Hong2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hong, S., Ka, S., Kim, S., Park, Y., Kang, S.
|
|
<strong>p80 coilin, a coiled body-specific protein, interacts with ataxin-1, the SCA1 gene product.</strong>
|
|
Biochim. Biophys. Acta 1638: 35-42, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12757932/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12757932</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12757932" 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/s0925-4439(03)00038-3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Jodice1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jodice, C., Malaspina, P., Persichetti, F., Novelletto, A., Spadaro, M., Giunti, P., Morocutti, C., Terrenato, L., Harding, A. E., Frontali, M.
|
|
<strong>Effect of trinucleotide repeat length and parental sex on phenotypic variation in spinocerebellar ataxia 1.</strong>
|
|
Am. J. Hum. Genet. 54: 959-965, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8198139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8198139</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8198139" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Kurosaki2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kurosaki, T., Ninokata, A., Wang, L., Ueda, S.
|
|
<strong>Evolutionary scenario for acquisition of CAG repeats in human SCA1 gene.</strong>
|
|
Gene 373: 23-27, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16497448/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16497448</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16497448" 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/j.gene.2005.12.017" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Lam2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lam, Y. C., Bowman, A. B., Jafar-Nejad, P., Lim, J., Richman, R., Fryer, J. D., Hyun, E. D., Duvick, L. A., Orr, H. T., Botas, J., Zoghbi, H. Y.
|
|
<strong>ATAXIN-1 interacts with the repressor Capicua in its native complex to cause SCA1 neuropathology.</strong>
|
|
Cell 127: 1335-1347, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17190598/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17190598</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17190598" 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/j.cell.2006.11.038" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Lim2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lim, J., Crespo-Barreto, J., Jafar-Nejad, P., Bowman, A. B., Richman, R., Hill, D. E., Orr, H. T., Zoghbi, H. Y.
|
|
<strong>Opposing effects of polyglutamine expansion on native protein complexes contribute to SCA1.</strong>
|
|
Nature 452: 713-718, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18337722/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18337722</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18337722[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=18337722" 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/nature06731" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Lim2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lim, J., Hao, T., Shaw, C., Patel, A. J., Szabo, G., Rual, J.-F., Fisk, C. J., Li, N., Smolyar, A., Hill, D. E., Barabasi, A.-L., Vidal, M., Zoghbi, H. Y.
|
|
<strong>A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration.</strong>
|
|
Cell 125: 801-814, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16713569/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16713569</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16713569" 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/j.cell.2006.03.032" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Matilla1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Matilla, A., Koshy, B. T., Cummings, C. J., Isobe, T., Orr, H. T., Zoghbi, H. Y.
|
|
<strong>The cerebellar leucine-rich acidic nuclear protein interacts with ataxin-1.</strong>
|
|
Nature 389: 974-978, 1997. Note: Erratum: Nature 391: 818 only, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9353121/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9353121</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9353121" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/40159" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Matilla1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Matilla, T., Volpini, V., Genis, D., Rosell, J., Corral, J., Davalos, A., Molins, A., Estivill, X.
|
|
<strong>Presymptomatic analysis of spinocerebellar ataxia type 1 (SCA1) via the expansion of the SCA1 CAG-repeat in a large pedigree displaying anticipation and parental male bias.</strong>
|
|
Hum. Molec. Genet. 2: 2123-2128, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8111382/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8111382</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8111382" 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/2.12.2123" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Mizutani2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mizutani, A., Wang, L., Rajan, H., Vig, P. J. S., Alaynick, W. A., Thaler, J. P., Tsai, C.-C.
|
|
<strong>Boat, an AXH domain protein, suppresses the cytotoxicity of mutant ataxin-1.</strong>
|
|
EMBO J. 24: 3339-3351, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16121196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16121196</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16121196[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=16121196" 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/sj.emboj.7600785" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Okazawa2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Okazawa, H., Rich, T., Chang, A., Lin, X., Waragai, M., Kajikawa, M., Enokido, Y., Komuro, A., Kato, S., Shibata, M., Hatanaka, H., Mouradian, M. M., Sudol, M., Kanazawa, I.
|
|
<strong>Interaction between mutant ataxin-1 and PQBP-1 affects transcription and cell death.</strong>
|
|
Neuron 34: 701-713, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12062018/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12062018</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12062018" 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(02)00697-9" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Okuda2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Okuda, T., Hattori, H., Takeuchi, S., Shimizu, J., Ueda, H., Palvimo, J. J., Kanazawa, I., Kawano, H., Nakagawa, M., Okazawa, H.
|
|
<strong>PQBP-1 transgenic mice show a late-onset motor neuron disease-like phenotype.</strong>
|
|
Hum. Molec. Genet. 12: 711-725, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12651867/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12651867</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12651867" 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/ddg084" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Orr1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Orr, H. T., Chung, M., Banfi, S., Kwiatkowski, T. J., Jr., Servadio, A., Beaudet, A. L., McCall, A. E., Duvick, L. A., Ranum, L. P. W., Zoghbi, H. Y.
|
|
<strong>Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1.</strong>
|
|
Nature Genet. 4: 221-226, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8358429/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8358429</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8358429" 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/ng0793-221" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Orr2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Orr, H. T., Zoghbi, H. Y.
|
|
<strong>SCA1 molecular genetics: a history of a 13 year collaboration against glutamines.</strong>
|
|
Hum. Molec. Genet. 10: 2307-2311, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11673415/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11673415</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11673415" 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/10.20.2307" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Serra2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Serra, H. G., Byam, C. E., Lande, J. D., Tousey, S. K., Zoghbi, H. Y., Orr, H. T.
|
|
<strong>Gene profiling links SCA1 pathophysiology to glutamate signaling in Purkinje cells of transgenic mice.</strong>
|
|
Hum. Molec. Genet. 13: 2535-2543, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15317756/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15317756</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15317756" 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/ddh268" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Serra2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Serra, H. G., Duvick, L., Zu, T., Carlson, K., Stevens, S., Jorgensen, N., Lysholm, A., Burright, E., Zoghbi, H. Y., Clark, H. B., Andresen, J. M., Orr, H. T.
|
|
<strong>ROR-alpha-mediated Purkinje cell development determines disease severity in adult SCA1 mice.</strong>
|
|
Cell 127: 697-708, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17110330/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17110330</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17110330" 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/j.cell.2006.09.036" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Servadio1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Servadio, A., Koshy, B., Armstrong, D., Antalffy, B., Orr, H. T., Zoghbi, H. Y.
|
|
<strong>Expression analysis of the ataxin-1 protein in tissues from normal and spinocerebellar ataxia type 1 individuals.</strong>
|
|
Nature Genet. 10: 94-98, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7647801/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7647801</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7647801" 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/ng0595-94" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Sisodia1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sisodia, S. S.
|
|
<strong>Nuclear inclusions in glutamine repeat disorders: are they pernicious, coincidental, or beneficial?</strong>
|
|
Cell 95: 1-4, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9778239/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9778239</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9778239" 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/s0092-8674(00)81743-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Skinner1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Skinner, P. J., Koshy, B. T., Cummings, C. J., Klement, I. A., Helin, K., Servadio, A., Zoghbi, H. Y., Orr, H. T.
|
|
<strong>Ataxin-1 with an expanded glutamine tract alters nuclear matrix-associated structures.</strong>
|
|
Nature 389: 971-974, 1997. Note: Erratum: Nature 39: 307 only, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9353120/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9353120</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9353120" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/40153" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Tong2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tong, X., Gui, H., Jin, F., Heck, B. W., Lin, P., Ma, J., Fondell, J. D., Tsai, C.-C.
|
|
<strong>Ataxin-1 and brother of ataxin-1 are components of the Notch signalling pathway.</strong>
|
|
EMBO Rep. 12: 428-435, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21475249/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21475249</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21475249[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=21475249" 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/embor.2011.49" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Tsai2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tsai, C.-C., Kao, H.-Y., Mitzutani, A., Banayo, E., Rajan, H., McKeown, M., Evans, R. M.
|
|
<strong>Ataxin 1, a SCA1 neurodegenerative disorder protein, is functionally linked to the silencing mediator of retinoid and thyroid hormone receptors.</strong>
|
|
Proc. Nat. Acad. Sci. 101: 4047-4052, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15016912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15016912</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15016912[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=15016912" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.0400615101" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Verhoef2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Verhoef, L. G. G. C., Lindsten, K., Masucci, M. G., Dantuma, N. P.
|
|
<strong>Aggregate formation inhibits proteasomal degradation of polyglutamine proteins.</strong>
|
|
Hum. Molec. Genet. 11: 2689-2700, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12374759/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12374759</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12374759" 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/11.22.2689" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Volz1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Volz, A., Boyle, J. M., Cann, H. M., Cottingham, R. W., Orr, H. T., Ziegler, A.
|
|
<strong>Report of the second international workshop on human chromosome 6.</strong>
|
|
Genomics 21: 464, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8088851/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8088851</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8088851" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1994.1302" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Watase2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Watase, K., Venken, K. J. T., Sun, Y., Orr, H. T., Zoghbi, H. Y.
|
|
<strong>Regional differences of somatic CAG repeat instability do not account for selective neuronal vulnerability in a knock-in mouse model of SCA1.</strong>
|
|
Hum. Molec. Genet. 12: 2789-2795, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12952864/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12952864</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12952864" 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/ddg300" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Yue2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yue, S., Serra, H. G., Zoghbi, H. Y., Orr, H. T.
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<strong>The spinocerebellar ataxia type 1 protein, ataxin-1, has RNA-binding activity that is inversely affected by the length of its polyglutamine tract.</strong>
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Hum. Molec. Genet. 10: 25-30, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11136710/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11136710</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11136710" 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/10.1.25" target="_blank">Full Text</a>]
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<a id="37" class="mim-anchor"></a>
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<a id="Zuhlke2002" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zuhlke, C., Dalski, A., Hellenbroich, Y., Bubel, S., Schwinger, E., Burk, K.
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<strong>Spinocerebellar ataxia type 1 (SCA1): Phenotype-genotype correlation studies in intermediate alleles.</strong>
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Europ. J. Hum. Genet. 10: 204-209, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11973625/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11973625</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11973625" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/sj.ejhg.5200788" target="_blank">Full Text</a>]
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Bao Lige - updated : 08/20/2018
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<div class="row collapse" id="mimCollapseContributors">
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<span class="mim-text-font">
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Patricia A. Hartz - updated : 11/1/2013<br>Cassandra L. Kniffin - updated : 5/20/2013<br>Ada Hamosh - updated : 11/29/2011<br>Patricia A. Hartz - updated : 10/21/2011<br>Matthew B. Gross - updated : 5/7/2009<br>Patricia A. Hartz - updated : 1/14/2009<br>Ada Hamosh - updated : 5/21/2008<br>George E. Tiller - updated : 6/21/2007<br>Victor A. McKusick - updated : 4/4/2007<br>Patricia A. Hartz - updated : 8/9/2006<br>George E. Tiller - updated : 1/31/2006<br>Patricia A. Hartz - updated : 10/20/2005<br>Patricia A. Hartz - updated : 8/23/2005<br>George E. Tiller - updated : 2/17/2005<br>Victor A. McKusick - updated : 5/13/2004<br>George E. Tiller - updated : 2/12/2004<br>Dawn Watkins-Chow - updated : 12/2/2003<br>Cassandra L. Kniffin - updated : 9/22/2003<br>Stylianos E. Antonarakis - updated : 7/3/2003<br>Michael B. Petersen - updated : 11/1/2002<br>Cassandra L. Kniffin - reorganized : 8/14/2002<br>George E. Tiller - updated : 2/13/2002<br>George E. Tiller - updated : 3/15/2001<br>George E. Tiller - updated : 12/12/2000<br>Stylianos E. Antonarakis - updated : 10/8/1998<br>Stylianos E. Antonarakis - updated : 10/8/1998<br>Ethylin Wang Jabs - updated : 7/21/1997
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<a id="creationDate" class="mim-anchor"></a>
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Creation Date:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 12/5/1996
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<span class="mim-text-font">
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alopez : 10/31/2019
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<span class="mim-text-font">
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mgross : 08/20/2018<br>alopez : 06/23/2016<br>mgross : 12/22/2015<br>mgross : 11/1/2013<br>carol : 5/28/2013<br>ckniffin : 5/20/2013<br>terry : 12/20/2012<br>alopez : 11/30/2011<br>terry : 11/29/2011<br>mgross : 10/26/2011<br>mgross : 10/21/2011<br>terry : 10/21/2011<br>terry : 11/3/2010<br>wwang : 5/11/2009<br>mgross : 5/7/2009<br>mgross : 1/14/2009<br>alopez : 5/27/2008<br>alopez : 5/27/2008<br>terry : 5/21/2008<br>terry : 5/21/2008<br>terry : 9/20/2007<br>wwang : 6/25/2007<br>terry : 6/21/2007<br>alopez : 4/10/2007<br>terry : 4/4/2007<br>wwang : 8/17/2006<br>wwang : 8/10/2006<br>terry : 8/9/2006<br>wwang : 2/6/2006<br>terry : 1/31/2006<br>mgross : 10/26/2005<br>terry : 10/20/2005<br>mgross : 8/23/2005<br>wwang : 2/22/2005<br>terry : 2/17/2005<br>tkritzer : 11/9/2004<br>terry : 11/2/2004<br>alopez : 5/13/2004<br>alopez : 5/13/2004<br>terry : 5/13/2004<br>cwells : 2/12/2004<br>mgross : 12/2/2003<br>carol : 11/14/2003<br>carol : 9/25/2003<br>ckniffin : 9/22/2003<br>carol : 7/7/2003<br>mgross : 7/3/2003<br>cwells : 11/1/2002<br>carol : 8/14/2002<br>ckniffin : 8/13/2002<br>cwells : 2/18/2002<br>cwells : 2/13/2002<br>cwells : 3/20/2001<br>cwells : 3/15/2001<br>cwells : 3/13/2001<br>carol : 12/13/2000<br>terry : 12/12/2000<br>carol : 10/8/1998<br>carol : 10/8/1998<br>terry : 9/9/1998<br>mark : 8/1/1997<br>mark : 8/1/1997<br>terry : 12/5/1996<br>terry : 12/5/1996<br>mark : 12/5/1996
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<span class="mim-font">
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<strong>*</strong> 601556
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<h3>
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ATAXIN 1; ATXN1
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Other entities represented in this entry:
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<span class="h3 mim-font">
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ATXN1, ALTERNATIVE READING FRAME, INCLUDED
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<span class="h4 mim-font">
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ALT-ATXN1, INCLUDED
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: ATXN1</em></strong>
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<strong>SNOMEDCT:</strong> 715748006;
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<em>
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Cytogenetic location: 6p22.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 6:16,299,112-16,761,460 </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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<strong>Gene-Phenotype Relationships</strong>
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<table class="table table-bordered table-condensed small mim-table-padding">
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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<span class="mim-font">
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6p22.3
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<span class="mim-font">
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Spinocerebellar ataxia 1
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</span>
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</td>
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<td>
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<span class="mim-font">
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164400
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<span class="mim-font">
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Autosomal dominant
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<span class="mim-font">
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3
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<span class="mim-font">
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<strong>TEXT</strong>
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<span class="mim-font">
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<strong>Description</strong>
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<span class="mim-text-font">
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<p>ATXN1 binds RNA, associates with large protein complexes, and interacts with a vast network of proteins. ATXN1 is thought to be involved in transcriptional repression and to regulate Notch (see 190198)- and Capicua (CIC; 612082)-controlled developmental processes (summary by Bergeron et al., 2013). </p>
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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 class="mim-text-font">
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<p>Using DNA fragments from a cosmid clone shown to contain the CAG trinucleotide repeat identified as the cause of spinocerebellar ataxia-1 (SCA1; 164400) by Orr et al. (1993), Banfi et al. (1994) screened 2 human fetal brain and 1 human adult cerebellar cDNA libraries to isolate the ATXN1 transcript. Banfi et al. (1994) demonstrated that the ATXN1 gene encodes an 816-amino acid protein with a molecular mass of 87 kD. The (CAG)n repeat, coding for a polyglutamine tract, lies within the coding region, and the protein is transcribed from both the wildtype and the CAG-expanded ATXN1 allele. </p><p>Mizutani et al. (2005) stated that the deduced 816-amino acid ATXN1 protein has an N-terminal BOAT (ATXN1L; 614301) and ataxin-1 (NBA) domain, followed by the polyglutamine tract, a self-association region (SAR), and a C-terminal ATXN1 and HBP1 (616714) (AXH) domain. </p><p>By immunoblot analysis, Servadio et al. (1995) demonstrated that the ATXN1 protein was present in various brain regions and in nonneuronal tissues, such as heart, skeletal muscle, and liver. Whereas it was located predominantly in cytoplasm in nonneuronal tissue, it was found in nuclei in neurons of the basal ganglia, pons, and cortex, and in both cytoplasm and nuclei of Purkinje cells of the cerebellum. Servadio et al. (1995) found that the protein varied in its size and electrophoretic migration properties according to the size of the (CAG)n repeat. </p><p><strong><em>Alternative ATXN1</em></strong></p><p>
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Bergeron et al. (2013) identified an alternative translation initiation codon in the +3 reading frame of ATXN1. Translation of alternative ATXN1 (ALT-ATXN1) begins 30 nucleotides downstream of the initiation codon of full-length ATXN1 and ends at nucleotide 587, just prior to the CAG repeat region. The deduced 185-amino acid protein has a calculated molecular mass of 21 kD. ALT-ATXN1 contains 26 proline residues distributed throughout the molecule, and it has a putative N-terminal proline-lysine (PY)-type nuclear localization signal. ALT-ATXN1 shares no sequence similarity with ATXN1. Bergeron et al. (2013) also identified a second putative 151-amino acid ALT-ATXN1 protein that is N-terminally truncated compared with the longer ALT-ATXN1 protein. Database analysis revealed orthologs of ALT-ATXN1 in several mammalian species and in chicken. Western blot analysis detected both ATXN1 and ALT-ATXN1 in normal human cerebellum and in primary cells cultured from a glioblastoma patient. Epitope-tagged ALT-ATXN1 colocalized with ATXN1 in nuclear inclusions and in the nucleoplasm of transfected cells. </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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<span class="mim-text-font">
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<p>Banfi et al. (1994) determined that ATXN1 gene spans 450 kb of genomic DNA and is organized into 9 exons. The first 7 fall in the 5-prime untranslated region, whereas the last 2 contain the coding region and a 7,277 bp 3-prime untranslated region. The first 4 noncoding exons undergo alternative splicing in several tissues. These features suggest that the transcriptional and translational regulation of ataxin-1 may be complex. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>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>Detailed linkage studies of families with SCA1 established the disease locus on chromosome 6 (see 164400), and Volz et al. (1994) reported that the ATXN1 gene had been mapped to 6p23 by in situ hybridization. </p><p>Servadio et al. (1995) mapped the mouse homolog of the ATXN1 gene to mouse chromosome 13. </p>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<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>Servadio et al. (1995) found that ATXN1 protein exhibited a normal nuclear/cytoplasmic localization in cultured cells and tissues from individuals with SCA1. Thus, the data showed that the mutant expanded ATXN1 alleles are faithfully translated into proteins of apparently normal stability and distribution. </p><p>Cummings et al. (1999) found that wildtype ataxin-1 and mutant ataxin-1 with an expanded polyglutamine tract were polyubiquitinated equally well in transfected HeLa cells in vitro, but the mutant form was 3 times more resistant to degradation. Inhibiting proteasomal degradation promoted aggregation of mutant ataxin-1. Mouse Purkinje cells expressing mutant ataxin-1 but not the ubiquitin-protein ligase Ube3a (601623) showed fewer ubiquitin-positive nuclear inclusions than Sca1 mice, but the Purkinje cell pathology was markedly worse. Cummings et al. (1999) concluded that nuclear inclusions are not necessary to induce neurodegeneration, but impaired proteasomal degradation of mutant ataxin-1 may contribute to SCA1 pathogenesis. </p><p>Davidson et al. (2000) identified an ataxin-1-interacting protein, A1U (605440), that localized to the nucleus and cytoplasm of transfected COS-1 cells. A1U contains an N-terminal ubiquitin-like region and has substantial homology to human UBQLN2 (300264), a protein that binds the ATPase domain of the HSP70-like Stch protein (601100). The authors suggested that A1U may link ataxin-1 with the chaperone and ubiquitin/proteasome pathways, and that ataxin-1 may function in the formation and regulation of multimeric protein complexes within the nucleus. </p><p>Using an in vitro RNA-binding assay, Yue et al. (2001) demonstrated that ataxin-1 binds RNA, and that this binding diminishes as the length of its polyglutamine tract increases. The authors suggested that ataxin-1 plays a role in RNA metabolism and that the expansion of the polyglutamine tract may alter this function. </p><p>Okazawa et al. (2002) proposed that modified transcription may underlie polyglutamine-mediated pathology and that polyglutamine-binding protein-1 (PQBP1; 300463) may be involved in the pathology of SCA1. Using in vitro and in vivo assays, they showed that interaction between ataxin-1 and PQBP1 was positively influenced by expanded polyglutamine sequences. In immunoprecipitation experiments, mutant ataxin-1 enhanced interaction between PQBP1 and the RNA polymerase II (pol II) large subunit (180660), and the authors proposed that a ternary complex is formed by PQBP1 in the presence of mutant ataxin-1. PQBP1 and mutant ataxin-1 acted cooperatively in cell lines to repress transcription and induce cell death. Okazawa et al. (2002) hypothesized that high expression of PQBP1 in the cerebellum promotes mutant ataxin-1-induced cell death, contributing to the region-specific neurodegeneration seen in SCA1 patient tissues. </p><p>To investigate the effect of expanded poly(Q) repeats on ubiquitin/proteasome-dependent proteolysis, Verhoef et al. (2002) targeted these proteins for proteasomal degradation by the introduction of an N-end rule degradation signal (i.e., N-terminal arginine residue). While soluble poly(Q) proteins were degraded, they resisted proteasomal degradation once present in the aggregates. Stabilization was also observed for proteins that are co-aggregated via interaction with the expanded poly(Q) domain. Introduction of a degradation signal in ataxin-1/Q92 reduced the incidence of nuclear inclusions and the cellular toxicity, conceivably by accelerating the clearance of the soluble substrate. </p><p>Chen et al. (2003) discovered that the 14-3-3 protein (see 113508), a multifunctional regulatory molecule, mediates the neurotoxicity of ataxin-1 by binding and stabilizing it, thereby slowing its normal degradation. The association of ataxin-1 with 14-3-3 was found to be regulated by AKT (164730) phosphorylation, and in a Drosophila model of SCA1, both 14-3-3 and Akt modulated neurodegeneration. The authors concluded that their finding that phosphatidylinositol 3-kinase/Akt signaling and 14-3-3 cooperate to modulate the neurotoxicity of ataxin-1 provides insight into SCA1 pathogenesis and identifies potential targets for therapeutic intervention. </p><p>The pathologic hallmark of neurodegenerative disorders associated with expanded polyglutamine repeats (polyQ) is the cytoplasmic or intranuclear accumulation of polyglutamine inclusions. Emamian et al. (2003) noted that the expanded tract may influence the behavior of the host protein and that elements of the protein outside of the polyglutamine tract may influence the course of disease. In vitro, Emamian et al. (2003) found that ataxin-1 is phosphorylated at ser776 and that most cells expressing ataxin-1(82Q)-ser776 contained large nuclear inclusions (60%), compared to cells expressing a mutant ataxin-1(82Q)-ala776 (less than 0.1%). Ataxin-1(82Q)-ala776 transgenic mice expressed the protein in Purkinje cell nuclei, but progression and manifestations of disease were substantially reduced. The authors concluded that polyglutamine tract expansion and intranuclear localization are not sufficient to induce disease, and that the ser776 phosphorylation site has a critical role in SCA1 pathogenesis. </p><p>By yeast 2-hybrid analysis, Hong et al. (2003) found that ataxin-1 interacted with coilin (COIL; 600272). Mutation analysis indicated that the C-terminal regions of both proteins mediated the interaction. HeLa cells cotransfected with ataxin-1 and coilin showed colocalization of the 2 proteins in aggregates in the nucleoplasm. A mutant form of ataxin-1 containing a polyglutamine expansion also interacted with coilin and localized with some coiled bodies, but it had no effect on their normal nuclear distribution. </p><p>Skinner et al. (1997) and Matilla et al. (1997) showed that, in transfected cells, both wildtype (30 glutamines) and mutant (82 glutamines) Atx1 localized to small dense nuclear bodies. Tsai et al. (2004) demonstrated that Atx1 interacts with the transcriptional corepressor SMRT (silencing mediator for retinoid and thyroid hormone receptors; 600848) and with histone deacetylase-3 (HDAC3; 605166). Atx1 binds chromosomes and mediates transcriptional repression when tethered to DNA. Interaction with SMRT-related factors is a conserved feature of Atx1, because Atx1 also binds SMRTER, a Drosophila cognate of SMRT. Significantly, mutant Atx1 forms aggregates in Drosophila, and such mutant Atx1-mediated aggregates sequester SMRTER. Consistently, the neurodegenerative eye phenotype in Drosophila caused by mutant Atx1 was enhanced by a Smrter mutation and, conversely, was suppressed by a chromosomal duplication that contained the wildtype Smrter gene. Tsai et al. (2004) interpreted their results as suggesting that Atx1 is a transcriptional factor whose mutant form exerts its deleterious effects in part by perturbing corepressor-dependent transcriptional pathways. </p><p>By yeast 2-hybrid and mutation analysis, Mizutani et al. (2005) showed that AXH domain of ATXN1 was required for its interaction with SMRT. Yeast 2-hybrid analysis also showed that ATXN1 interacted with BOAT (ATXN1L), and Mizutani et al. (2005) confirmed the interaction between BOAT and ATXN1 in human cell culture and Drosophila. Truncation analysis showed that the NBA domain of BOAT mediated its self-association and interaction with ATXN1, whereas the SAR and NBA domains of ATXN1 mediated its self-association and interaction with BOAT. Mutation analysis and reporter gene assays revealed that the AXH domain of ATXN1 was required for transcriptional repression, likely due to its interaction with SMRT. Truncation analysis and reporter gene assays revealed that ATXN1 contains a C-terminal transcriptional repressive domain, whereas BOAT contains independent N- and C-terminal transcriptional repressive domains. Immunoprecipitation analysis showed that endogenous BOAT, SMRT, and ATXN1 interacted in a complex in HeLa cells. Expression of ATXN1 with a polyglutamine expansion (82Q) caused an abnormal eye phenotype in Drosophila, and this phenotype was reversed by coexpression of BOAT. Expression of ATXN1 without the polyglutamine tract (0Q) also caused an abnormal eye phenotype in Drosophila, although it was less severe than that caused by ATXN1(82Q). SCA1 mice, which express human mutant ATXN1 in Purkinje cells, showed reduced expression of both Boat and Smrt compared with wildtype mice. Mizutani et al. (2005) hypothesized that BOAT inhibits mutant ATXN1 toxicity by dimerizing with ATXN1 and reducing mutant ATXN1 self-association. </p><p>Lam et al. (2006) examined soluble protein complexes from mouse cerebellum and found that the majority of wildtype and expanded Atxn1 assembles into large stable complexes containing the transcriptional repressor Capicua (Cic; 612082). Atxn1 directly bound Cic and modulated Cic repressor activity in Drosophila and mammalian cells, and its loss decreased the steady state level of Cic. Interestingly, the S776A mutation, which abrogates the neurotoxicity of expanded Atxn1, substantially reduced the association of mutant Atxn1 with Cic in vivo. Lam et al. (2006) concluded that their data provided insight into the function of Atxn1 and suggested that the neuropathology of SCA1 (164400), caused by expansion of the ATXN1 polyglutamine tract, depends on native, not novel, protein interactions. Lam et al. (2006) found that the majority of CIC associates with ATXN1 in vivo and that ATXN1 binds CIC through an 8-amino-acid sequence conserved across species. </p><p>Using yeast 2-hybrid screens, coaffinity purification analysis of transfected HEK293 cells, and bioinformatic analysis, Lim et al. (2006) developed an interaction network for 54 human proteins involved in 23 inherited ataxias. By database analysis, they expanded the core network to include more distantly related interacting proteins that could function as genetic modifiers. A majority (18 of 23) of ataxia-causing proteins interacted either directly or indirectly. ATXN1 showed strong direct interactions with ATXN2 (601517) and RBPMS (601558), and the N-terminal portion of ATXN1 was required for interaction with RBPMS. RBPMS was a main hub in the network and interacted with many proteins, including 2 cerebellar ataxia-associated proteins, ATN1 (607462) and QK1 (609590). The ATXN1 interactor COIL also interacted with the ataxia-associated protein puratrophin-1 (PLEKHG4; 609526). </p><p>Lim et al. (2008) demonstrated that the expanded polyglutamine tract of ATXN1 differentially affects the function of the host protein in the context of different endogenous protein complexes. Polyglutamine expansion in ATXN1 favors the formation of a particular protein complex containing RBM17 (606935), contributing to SCA1 neuropathology by means of a gain-of-function mechanism. Concomitantly, polyglutamine expansion attenuates the formation and function of another protein complex containing ATXN1 and capicua, contributing to SCA1 through a partial loss-of-function mechanism. Lim et al. (2008) concluded that their model provides mechanistic insight into the molecular pathogenesis of SCA1 as well as other polyglutamine diseases. </p><p>Notch signaling involves proteolytic release of the Notch intracellular domain (NICD), followed by NICD-dependent gene activation. Tong et al. (2011) found that expression of human BOAT1 in Drosophila wing disrupted Notch signaling, leading to wing defects. Coimmunoprecipitation analysis of HEK293 cells revealed that both BOAT1 and ATXN1 precipitated CBF1 (RBPJ; 147183), which functions as a transcriptional activator when associated with NICD. Protein pull-down and yeast 2-hybrid analyses confirmed the interactions and showed that BOAT1 and ATXN1 competed for CBF1 binding. Coimmunoprecipitation experiments showed that NICD disrupted CBF1-BOAT/ATXN1 interactions. Reporter gene assays revealed that both BOAT1 and ATXN1 inhibited CBF1 activity at the HEY1 (602953) promoter. Chromatin immunoprecipitation assays showed that Boat1 and Atxn1, in addition to Smrt, occupied the Hey1 promoter in differentiating mouse C2C12 myoblasts. Atxn1 bound the Hey1 promoter transiently, whereas Boat1 and Smrt remained bound to the Hey1 promoter under the same conditions. Tong et al. (2011) concluded that BOAT1 and ATXN1 are chromatin-binding factors that repress Notch signaling in the absence of NCID by acting as CBF1 corepressors. </p><p><strong><em>Alternative ATXN1</em></strong></p><p>
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Using coimmunoprecipitation and protein pull-down assays, Bergeron et al. (2013) found that ALT-ATXN1 interacted directly with ATXN1. Deletion analysis revealed that ALT-ATXN1 interacted with an N-terminal domain of ATXN1 and not with the polyglutamine track. Neither ATXN1 nor ALT-ATXN1 directly affected expression or solubility of the other protein, and ALT-ATXN1 translation was independent of the number of CAG repeats in the transcript. ATXN1 spontaneously formed intranuclear inclusion in the absence of ALT-ATXN1 and recruited ALT-ATXN1 to these inclusions. ALT-ATXN1 also bound to poly(A) RNA. </p>
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<strong>Molecular Genetics</strong>
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<p><strong><em>ATXN1 Polyglutamine Expansion in SCA1</em></strong></p><p>
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Orr et al. (1993) demonstrated that the basic defect in spinocerebellar ataxia-1 (164400) consists of expansion of a trinucleotide CAG repeat (601556.0001) and Banfi et al. (1994) identified the gene as ataxin-1. Both groups showed that the repeat is present not only in genomic DNA but also in a 10-kb mRNA transcript. </p><p>Sisodia (1998) reviewed the significance of nuclear inclusions in glutamine repeat disorders. </p><p>Orr and Zoghbi (2001) reviewed the history of unraveling the molecular pathogenesis of SCA1. </p><p><strong><em>Genetic Anticipation</em></strong></p><p>
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Chung et al. (1993) found that 63% of paternal transmissions of the mutant allele show an increase in repeat number, whereas 69% of maternal transmissions show no change or a decrease in repeat number. Sequence analysis showed that 98% of unexpanded alleles had an interrupted repeat configuration, whereas a contiguous repeat (CAG)n was found in expanded alleles. This indicated that the repeat instability in ATXN1 is more complex than a simple variation in repeat number and that the loss of an interruption predisposes the ATXN1 (CAG)n to expansion. Matilla et al. (1993) studied the expansion of the ATXN1 gene CAG repeat in a large family in which spinocerebellar ataxia showed the phenomenon of anticipation. There were 41 affected members with no juvenile cases of SCA1, the mean age of onset being 36 years. The family also showed the phenomenon of parental male bias; i.e., the age of onset was younger and the duration of illness before death was shorter in the members of the family who inherited the disorder from the father. In this large Spanish kindred, Matilla et al. (1993) found 9 clinically unaffected persons between ages 18 and 40 years who had expansions of the CAG repeat within the pathogenetic range. In 22 other genetically 'at risk' individuals, they found that the number of (CAG)n repeats in the ATXN1 gene was within the normal range. </p><p>Jodice et al. (1994) found trinucleotide repeat expansion in 64 subjects from 19 families: 57 patients with SCA1 and 7 subjects predicted, by haplotype analysis, to carry the mutation. Comparison with a large set of normal chromosomes showed 2 distinct distributions with a much wider variation among expanded chromosomes. The sex of the transmitting parent played a major role in the size distribution of expanded alleles, those with more than 54 repeats being transmitted by affected fathers exclusively. Alleles with 46 to 54 repeats were transmitted by affected fathers and mothers in equal proportions. On the other hand, the sex ratio of offspring receiving either more than 54 or less than 54 repeats approached the expected 50:50. If a steady-state distribution of repeat numbers is assumed to persist through the generations, this raises the question as to why affected females transmitting alleles with more than 54 repeats are lacking, while females receiving more than 54 repeats exist. This may be explained, at least in part, by reduced biologic fitness. Detailed clinical follow-up of a subset of patients by Jodice et al. (1994) demonstrated significant relationships between increasing repeat number on expanded chromosomes and earlier age at onset, faster progression of the disease, and earlier age at death. </p><p><strong><em>Association with Schizophrenia</em></strong></p><p>
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For discussion of a possible association between the ATXN1 CAG repeat and risk of schizophrenia, see SCZD3 (600511).</p>
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<span class="mim-font">
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<strong>Evolution</strong>
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<p>In order to determine how the human ATXN1 gene acquired the CAG repeat structure with interruptions, Kurosaki et al. (2006) analyzed the Atxn1 gene in many primate species, rat, and mouse. They found no repeats in the corresponding region of rodent, prosimian, and New World monkey Atxn1 genes. They found perfect uninterrupted CAG repeats in Old World monkeys and interrupted CAG repeats in hominoids. Kurosaki et al. (2006) concluded that there was no repetitive CAG structure in the common ancestor of primates and that the interrupted repetitive structure of the human ATXN1 gene was gradually acquired during evolution of the simian lineage. </p>
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<strong>Animal Model</strong>
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<p>Banfi et al. (1996) found that murine Sca1 and human ataxin-1 are highly homologous but the CAG repeat is virtually absent in the mouse sequence, suggesting that the polyglutamine stretch is not essential for the normal function of ataxin-1 in mice. Cellular and developmental expression of the murine homolog was examined using RNA in situ hybridization. During cerebellar development, there is a transient burst of Sca1 expression at postnatal day 14, when the murine cerebellar cortex becomes physiologically functional. There was also marked expression of Sca1 in mesenchymal cells of the intervertebral discs during development of the spinal column. The results suggested to the authors that the normal Sca1 gene has a role at specific stages of both cerebellar and vertebral column development. </p><p>PQBP1 (300463) is a polyglutamine-binding nuclear protein which has been shown to interact with ataxin-1. Okuda et al. (2003) generated transgenic mice overexpressing human PQBP1. The mice showed a late-onset and gradually progressive motor neuron disease-like phenotype suggestive of the neurogenic muscular atrophy observed in SCA1 patients. Ataxia could not be discriminated from predominant progressive weakness. Pathologic examinations of the transgenic mice revealed loss of Purkinje and granular cells in the cerebellum as well as loss of motor neurons in the spinal anterior horn, corresponding to the pathology of human SCA1. Okuda et al. (2003) concluded that excessive action of PQBP1 causes neuronal dysfunction and that PQBP1 may be involved in the pathology of SCA1. </p><p>Watase et al. (2003) investigated the pattern of CAG repeat instability in a knockin mouse model of SCA1. Small pool (SP)-PCR analysis on DNA from various neuronal and nonneuronal tissues revealed that somatic repeat instability was highest in the striatum. In the 2 SCA1-vulnerable tissues, cerebellum and spinal cord, there were substantial differences in the profile of mosaicism. Watase et al. (2003) suggested that in SCA1 there is no clear causal relationship between the degree of somatic instability and selective neuronal vulnerability. The finding that somatic instability is most pronounced in the striatum of various knockin models of polyglutamine diseases may suggest a role of trans-acting tissue- or cell-specific factors in mediating the instability. </p><p>Serra et al. (2004) used DNA microarrays to determine the pattern of gene expression in SCA1 transgenic mice at 5 weeks (prior to onset of pathology) and at 12 weeks (midpoint of disease progression). By comparing the pattern of gene expression in the SCA1 ataxic B05-ataxin-1(82Q) transgenic mouse line with those seen in 2 nonataxic lines, A02-ataxin-1(30Q) and K772T(82Q), 9 genes were identified whose expression was consistently altered in the cerebellum of B05(82Q) mice at 5 and 12 weeks of age. Five of the genes formed a biologic cohort centered on glutamate signaling pathways in Purkinje cells. </p><p>Using a conditional transgenic mouse model of SCA1, Serra et al. (2006) showed that delaying postnatal expression of mutant human ATXN1 until completion of cerebellar maturation led to a substantial reduction in disease severity in adults compared with early postnatal expression of mutant ATXN1. Microarray analysis revealed that genes regulated by Rora (600825), a transcription factor critical for cerebellar development, were downregulated at an early stage of disease in Purkinje cells of SCA1 transgenic mice. Rora mRNA and protein levels were reduced in Purkinje cells of SCA1 transgenic mice, and the effect of mutant ATXN1 on Rora protein levels appeared to be independent of its effect on Rora mRNA levels. Partial loss of Rora enhanced the pathogenicity of mutant ATXN1 in transgenic mice. Coimmunoprecipitation and pull-down analyses suggested the existence of a complex containing Atxn1, Rora, and the Rora coactivator Tip60 (HTATIP; 601409), with Atxn1 and Tip60 interacting directly. Serra et al. (2006) concluded that RORA and TIP60 have a role in SCA1 and proposed that their findings provide a mechanism by which compromised cerebellar development contributes to the severity of neurodegeneration in an adult. </p><p>Lam et al. (2006) determined that wildtype and polyglutamine-expanded Atxn1 associate into a group of large protein complexes containing the transcriptional repressor Capicua (CIC; 612082) in mouse cerebellum and differentially modify CIC activity. However, although specific interactions had been clearly implicated in neurotoxicity, it was unclear whether the neurotoxicity of the mutant protein occurred in its native state by association into normal endogenous protein complexes or by the aberrant interactions and new complexes formed by the misfolding or aggregating Atxn1. </p><p>Studies of the pathogenesis of SCA1 supported a model in which the expanded glutamine tract in the ATXN1 gene causes toxicity by modulating the normal activities of that gene. To explore native interactions that modify the toxicity of ATXN1, Bowman et al. (2007) generated a targeted duplication of mouse Ataxn1l and tested the role of this protein in SCA1 pathology. Using a knockin mouse model of SCA1 that recapitulates the selective neurodegeneration seen in affected individuals, Bowman et al. (2007) found that elevated Atxn1l levels suppress neuropathology by displacing mutant Atxn1 from its native complex with Capicua. The results provided genetic evidence that the selective neuropathology of SCA1 arises from modulation of a core functional activity of ATXN1, and they underscored the importance of studying the paralogs of genes mutated in neurodegenerative diseases to gain insight into mechanisms of pathogenesis. </p><p>Duvick et al. (2010) observed that transgenic Atxn1 mice with a wildtype glutamine tract (30Q) and expression of a ser776-to-asp (S776D) phosphogenic substitution developed pathologic changes in cerebellar Purkinje cells, such as dendritic atrophy and decreased arborization of climbing fibers, that resembled those of mice carrying only an expanded polyglutamine tract (82Q). D776/30Q mice also showed progressive motor dysfunction, similar to S776/82Q mice. However, the D776/30Q genotype did not induce cell death. The study showed that a single amino acid substitution outside of the polyQ tract converted wildtype Atxn1 into a toxic protein with the pathogenic capabilities of the protein with an expanded polyQ tract. Moreover, the D776 substitution enhanced the pathogenicity of Atxn1(82Q). The results supported a model in which disease pathogenesis involves changes in regions of the protein in addition to the polyglutamine tract. Alteration at ser776 was critical for neuronal dysfunction, but an expanded polyglutamine tract was necessary for neuronal death. Duvick et al. (2010) concluded that disease initiation and late-stage induction of neuronal death are distinct disease phases, and suggested that inhibiting phosphorylation may be a therapeutic strategy. </p><p>To determine the long-term effects of exercise, Fryer et al. (2011) implemented a mild exercise regimen in a mouse model of SCA1 and found a considerable improvement in survival accompanied by upregulation of epidermal growth factor and consequential downregulation of Capicua, which is an ATXN1 interactor. Offspring of Capicua mutant mice bred to Sca1 mice showed significant improvement of all disease phenotypes. Although polyglutamine-expanded Atxn1 caused some loss of Capicua function, further reduction of Capicua levels--either genetically or by exercise--mitigated the disease phenotypes by dampening the toxic gain of function. Fryer et al. (2011) concluded that exercise might have long-term beneficial effects in other ataxias and neurodegenerative diseases. </p><p>Edamakanti et al. (2018) studied SCA1 knockin mice in which one allele expressed Atxn1 with a pathogenic polyglutamine expansion and the other allele expressed normal mouse Atxn1. Knockin mice showed increased proliferation of postnatal cerebellar stem cells. These hyperproliferating stem cells tended to differentiate into GABAergic interneurons rather than astrocytes, which gave rise to a greater number of basket cells and stellate cells than Purkinje neurons. Cultures of cerebellar stem cells from knockin mice showed increased proliferation and differentiation in vitro, consistent with the in vivo analysis. The altered stem-cell phenotype in knockin mice appeared to be caused by a cell-autonomous gain of Atxn1 function within the cerebellar stem cells themselves. The authors also showed that more GABAergic synapses in the cerebella of knockin mice resulted in increased inhibitory synaptic connections to Purkinje neurons and disrupted cerebellar Purkinje cell function. </p>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>1 Selected Example):</strong>
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</span>
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</h4>
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<h4>
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<span class="mim-font">
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<strong>.0001 SPINOCEREBELLAR ATAXIA 1</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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ATXN1, (CAG)n REPEAT EXPANSION
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<br />
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SNP: rs193922926,
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ClinVar: RCV000008537
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<span class="mim-text-font">
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<p>The cause of spinocerebellar ataxia-1 (SCA1; 164400) is an expansion of a (CAG)n repeat in the gene encoding ataxin-1 located on 6p (Orr et al., 1993; Banfi et al., 1994). Most unexpanded alleles have an interrupted repeat configuration, whereas a contiguous repeat (CAG)n is found in expanded alleles. The repeat instability in ATXN1 is probably more complex than a simple variation in repeat number; the loss of an interruption predisposes the ATXN1 (CAG)n repeat to expansion. </p><p>Zuhlke et al. (2002) analyzed the CAG repeat length and composition in the ATXN1 gene in 16 individuals with alleles ranging from 36 to 43 triplets. Alleles with 36 to 38 triplets were present in individuals with ataxia but without additional characteristic features of SCA1. SCA1 phenotypes were found for patients with 41 and 43 triplets. The 39 triplet allele missing CAT interruptions was associated with symptoms characteristic for SCA1 in 4 patients, whereas the interrupted allele with 39 triplets did not cause characteristic SCA1 features in 1 individual. These findings suggested a change from normal to pathologic alleles at 39 triplets depending on the presence of CAT interruptions in the CAG repeat. Stable inheritance of the uninterrupted 39 triplet allele was observed in 1 familial case of SCA1. </p>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<p />
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<ol>
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Banfi, S., Servadio, A., Chung, M., Kwiatkowski, T. J., Jr., McCall, A. E., Duvick, L. A., Shen, Y., Roth, E. J., Orr, H. T., Zoghbi, H. Y.
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<strong>Identification and characterization of the gene causing type 1 spinocerebellar ataxia.</strong>
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Nature Genet. 7: 513-520, 1994.
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[PubMed: 7951322]
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[Full Text: https://doi.org/10.1038/ng0894-513]
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<li>
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<p class="mim-text-font">
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Banfi, S., Servadio, A., Chung, M.-y., Capozzoli, F., Duvick, L. A., Elde, R., Zoghbi, H. Y., Orr, H. T.
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<strong>Cloning and developmental expression analysis of the murine homolog of the spinocerebellar ataxia type 1 gene (Sca1).</strong>
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Hum. Molec. Genet. 5: 33-40, 1996.
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[PubMed: 8789437]
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[Full Text: https://doi.org/10.1093/hmg/5.1.33]
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<p class="mim-text-font">
|
|
Bergeron, D., Lapointe, C., Bissonnette, C., Tremblay, G., Motard, J., Roucou, X.
|
|
<strong>An out-of-frame overlapping reading frame in the ataxin-1 coding sequence encodes a novel ataxin-1 interacting protein.</strong>
|
|
J. Biol. Chem. 288: 21824-21835, 2013.
|
|
|
|
|
|
[PubMed: 23760502]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M113.472654]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bowman, A. B., Lam, Y. C., Jafar-Nejad, P., Chen, H.-K., Richman, R., Samaco, R. C., Fryer, J. D., Kahle, J. J., Orr, H. T., Zoghbi, H. Y.
|
|
<strong>Duplication of Atxn1l suppresses SCA1 neuropathology by decreasing incorporation of polyglutamine-expanded ataxin-1 into native complexes.</strong>
|
|
Nature Genet. 39: 373-379, 2007.
|
|
|
|
|
|
[PubMed: 17322884]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1977]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chen, H.-K., Fernandez-Funez, P., Acevedo, S. F., Lam, Y. C., Kaytor, M. D., Fernandez, M. H., Aitken, A., Skoulakis, E. M. C., Orr, H. T., Botas, J., Zoghbi, H. Y.
|
|
<strong>Interaction of Akt-phosphorylated ataxin-1 with 14-3-3 mediates neurodegeneration in spinocerebellar ataxia type 1.</strong>
|
|
Cell 113: 457-468, 2003.
|
|
|
|
|
|
[PubMed: 12757707]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0092-8674(03)00349-0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chung, M., Ranum, L. P. W., Duvick, L. A., Servadio, A., Zoghbi, H. Y., Orr, H. T.
|
|
<strong>Evidence for a mechanism predisposing to intergenerational CAG repeat instability in spinocerebellar ataxia type 1.</strong>
|
|
Nature Genet. 5: 254-258, 1993.
|
|
|
|
|
|
[PubMed: 8275090]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1193-254]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cummings, C. J., Reinstein, E., Sun, Y., Antalffy, B., Jiang, Y., Ciechanover, A., Orr, H. T., Beaudet, A. L., Zoghbi, H. Y.
|
|
<strong>Mutation of the E6-AP ubiquitin ligase reduces nuclear inclusion frequency while accelerating polyglutamine-induced pathology in SCA1 mice.</strong>
|
|
Neuron 24: 879-892, 1999.
|
|
|
|
|
|
[PubMed: 10624951]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0896-6273(00)81035-1]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Davidson, J. D., Riley, B., Burright, E. N., Duvick, L. A., Zoghbi, H. Y., Orr, H. T.
|
|
<strong>Identification and characterization of an ataxin-1-interactin g protein: A1Up, a ubiquitin-like nuclear protein.</strong>
|
|
Hum. Molec. Genet. 9: 2305-2312, 2000.
|
|
|
|
|
|
[PubMed: 11001934]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/oxfordjournals.hmg.a018922]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Duvick, L., Barnes, J., Ebner, B., Agrawal, S., Andresen, M., Lim, J., Giesler, G. J., Zoghbi, H. Y., Orr, H. T.
|
|
<strong>SCA1-like disease in mice expressing wild-type ataxin-1 with a serine to aspartic acid replacement at residue 776.</strong>
|
|
Neuron 67: 929-935, 2010.
|
|
|
|
|
|
[PubMed: 20869591]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.neuron.2010.08.022]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Edamakanti, C. R., Do, J., Didonna, A., Martina, M., Opal, P.
|
|
<strong>Mutant ataxin1 disrupts cerebellar development in spinocerebellar ataxia type 1.</strong>
|
|
J. Clin. Invest. 128: 2252-2265, 2018.
|
|
|
|
|
|
[PubMed: 29533923]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI96765]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Emamian, E. S., Kaytor, M. D., Duvick, L. A., Zu, T., Tousey, S. K., Zoghbi, H. Y., Clark, H. B., Orr, H. T.
|
|
<strong>Serine 776 of ataxin-1 is critical for polyglutamine-induced disease in SCA1 transgenic mice.</strong>
|
|
Neuron 38: 375-387, 2003.
|
|
|
|
|
|
[PubMed: 12741986]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0896-6273(03)00258-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fryer, J. D., Yu, P., Kang, H., Mandel-Brehm, C., Carter, A. N., Crespo-Barreto, J., Gao, V., Flora, A., Shaw, C., Orr, H. T., Zoghbi, H. Y.
|
|
<strong>Exercise and genetic rescue of SCA1 via the transcriptional repressor Capicua.</strong>
|
|
Science 334: 690-693, 2011.
|
|
|
|
|
|
[PubMed: 22053053]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1212673]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hong, S., Ka, S., Kim, S., Park, Y., Kang, S.
|
|
<strong>p80 coilin, a coiled body-specific protein, interacts with ataxin-1, the SCA1 gene product.</strong>
|
|
Biochim. Biophys. Acta 1638: 35-42, 2003.
|
|
|
|
|
|
[PubMed: 12757932]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0925-4439(03)00038-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jodice, C., Malaspina, P., Persichetti, F., Novelletto, A., Spadaro, M., Giunti, P., Morocutti, C., Terrenato, L., Harding, A. E., Frontali, M.
|
|
<strong>Effect of trinucleotide repeat length and parental sex on phenotypic variation in spinocerebellar ataxia 1.</strong>
|
|
Am. J. Hum. Genet. 54: 959-965, 1994.
|
|
|
|
|
|
[PubMed: 8198139]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kurosaki, T., Ninokata, A., Wang, L., Ueda, S.
|
|
<strong>Evolutionary scenario for acquisition of CAG repeats in human SCA1 gene.</strong>
|
|
Gene 373: 23-27, 2006.
|
|
|
|
|
|
[PubMed: 16497448]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.gene.2005.12.017]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lam, Y. C., Bowman, A. B., Jafar-Nejad, P., Lim, J., Richman, R., Fryer, J. D., Hyun, E. D., Duvick, L. A., Orr, H. T., Botas, J., Zoghbi, H. Y.
|
|
<strong>ATAXIN-1 interacts with the repressor Capicua in its native complex to cause SCA1 neuropathology.</strong>
|
|
Cell 127: 1335-1347, 2006.
|
|
|
|
|
|
[PubMed: 17190598]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.cell.2006.11.038]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lim, J., Crespo-Barreto, J., Jafar-Nejad, P., Bowman, A. B., Richman, R., Hill, D. E., Orr, H. T., Zoghbi, H. Y.
|
|
<strong>Opposing effects of polyglutamine expansion on native protein complexes contribute to SCA1.</strong>
|
|
Nature 452: 713-718, 2008.
|
|
|
|
|
|
[PubMed: 18337722]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature06731]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lim, J., Hao, T., Shaw, C., Patel, A. J., Szabo, G., Rual, J.-F., Fisk, C. J., Li, N., Smolyar, A., Hill, D. E., Barabasi, A.-L., Vidal, M., Zoghbi, H. Y.
|
|
<strong>A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration.</strong>
|
|
Cell 125: 801-814, 2006.
|
|
|
|
|
|
[PubMed: 16713569]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.cell.2006.03.032]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Matilla, A., Koshy, B. T., Cummings, C. J., Isobe, T., Orr, H. T., Zoghbi, H. Y.
|
|
<strong>The cerebellar leucine-rich acidic nuclear protein interacts with ataxin-1.</strong>
|
|
Nature 389: 974-978, 1997. Note: Erratum: Nature 391: 818 only, 1998.
|
|
|
|
|
|
[PubMed: 9353121]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/40159]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Matilla, T., Volpini, V., Genis, D., Rosell, J., Corral, J., Davalos, A., Molins, A., Estivill, X.
|
|
<strong>Presymptomatic analysis of spinocerebellar ataxia type 1 (SCA1) via the expansion of the SCA1 CAG-repeat in a large pedigree displaying anticipation and parental male bias.</strong>
|
|
Hum. Molec. Genet. 2: 2123-2128, 1993.
|
|
|
|
|
|
[PubMed: 8111382]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/2.12.2123]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mizutani, A., Wang, L., Rajan, H., Vig, P. J. S., Alaynick, W. A., Thaler, J. P., Tsai, C.-C.
|
|
<strong>Boat, an AXH domain protein, suppresses the cytotoxicity of mutant ataxin-1.</strong>
|
|
EMBO J. 24: 3339-3351, 2005.
|
|
|
|
|
|
[PubMed: 16121196]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.emboj.7600785]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Okazawa, H., Rich, T., Chang, A., Lin, X., Waragai, M., Kajikawa, M., Enokido, Y., Komuro, A., Kato, S., Shibata, M., Hatanaka, H., Mouradian, M. M., Sudol, M., Kanazawa, I.
|
|
<strong>Interaction between mutant ataxin-1 and PQBP-1 affects transcription and cell death.</strong>
|
|
Neuron 34: 701-713, 2002.
|
|
|
|
|
|
[PubMed: 12062018]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0896-6273(02)00697-9]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Okuda, T., Hattori, H., Takeuchi, S., Shimizu, J., Ueda, H., Palvimo, J. J., Kanazawa, I., Kawano, H., Nakagawa, M., Okazawa, H.
|
|
<strong>PQBP-1 transgenic mice show a late-onset motor neuron disease-like phenotype.</strong>
|
|
Hum. Molec. Genet. 12: 711-725, 2003.
|
|
|
|
|
|
[PubMed: 12651867]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddg084]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Orr, H. T., Chung, M., Banfi, S., Kwiatkowski, T. J., Jr., Servadio, A., Beaudet, A. L., McCall, A. E., Duvick, L. A., Ranum, L. P. W., Zoghbi, H. Y.
|
|
<strong>Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1.</strong>
|
|
Nature Genet. 4: 221-226, 1993.
|
|
|
|
|
|
[PubMed: 8358429]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0793-221]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Orr, H. T., Zoghbi, H. Y.
|
|
<strong>SCA1 molecular genetics: a history of a 13 year collaboration against glutamines.</strong>
|
|
Hum. Molec. Genet. 10: 2307-2311, 2001.
|
|
|
|
|
|
[PubMed: 11673415]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/10.20.2307]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Serra, H. G., Byam, C. E., Lande, J. D., Tousey, S. K., Zoghbi, H. Y., Orr, H. T.
|
|
<strong>Gene profiling links SCA1 pathophysiology to glutamate signaling in Purkinje cells of transgenic mice.</strong>
|
|
Hum. Molec. Genet. 13: 2535-2543, 2004.
|
|
|
|
|
|
[PubMed: 15317756]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddh268]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Serra, H. G., Duvick, L., Zu, T., Carlson, K., Stevens, S., Jorgensen, N., Lysholm, A., Burright, E., Zoghbi, H. Y., Clark, H. B., Andresen, J. M., Orr, H. T.
|
|
<strong>ROR-alpha-mediated Purkinje cell development determines disease severity in adult SCA1 mice.</strong>
|
|
Cell 127: 697-708, 2006.
|
|
|
|
|
|
[PubMed: 17110330]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.cell.2006.09.036]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Servadio, A., Koshy, B., Armstrong, D., Antalffy, B., Orr, H. T., Zoghbi, H. Y.
|
|
<strong>Expression analysis of the ataxin-1 protein in tissues from normal and spinocerebellar ataxia type 1 individuals.</strong>
|
|
Nature Genet. 10: 94-98, 1995.
|
|
|
|
|
|
[PubMed: 7647801]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0595-94]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sisodia, S. S.
|
|
<strong>Nuclear inclusions in glutamine repeat disorders: are they pernicious, coincidental, or beneficial?</strong>
|
|
Cell 95: 1-4, 1998.
|
|
|
|
|
|
[PubMed: 9778239]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0092-8674(00)81743-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Skinner, P. J., Koshy, B. T., Cummings, C. J., Klement, I. A., Helin, K., Servadio, A., Zoghbi, H. Y., Orr, H. T.
|
|
<strong>Ataxin-1 with an expanded glutamine tract alters nuclear matrix-associated structures.</strong>
|
|
Nature 389: 971-974, 1997. Note: Erratum: Nature 39: 307 only, 1998.
|
|
|
|
|
|
[PubMed: 9353120]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/40153]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tong, X., Gui, H., Jin, F., Heck, B. W., Lin, P., Ma, J., Fondell, J. D., Tsai, C.-C.
|
|
<strong>Ataxin-1 and brother of ataxin-1 are components of the Notch signalling pathway.</strong>
|
|
EMBO Rep. 12: 428-435, 2011.
|
|
|
|
|
|
[PubMed: 21475249]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/embor.2011.49]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tsai, C.-C., Kao, H.-Y., Mitzutani, A., Banayo, E., Rajan, H., McKeown, M., Evans, R. M.
|
|
<strong>Ataxin 1, a SCA1 neurodegenerative disorder protein, is functionally linked to the silencing mediator of retinoid and thyroid hormone receptors.</strong>
|
|
Proc. Nat. Acad. Sci. 101: 4047-4052, 2004.
|
|
|
|
|
|
[PubMed: 15016912]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0400615101]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Verhoef, L. G. G. C., Lindsten, K., Masucci, M. G., Dantuma, N. P.
|
|
<strong>Aggregate formation inhibits proteasomal degradation of polyglutamine proteins.</strong>
|
|
Hum. Molec. Genet. 11: 2689-2700, 2002.
|
|
|
|
|
|
[PubMed: 12374759]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/11.22.2689]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Volz, A., Boyle, J. M., Cann, H. M., Cottingham, R. W., Orr, H. T., Ziegler, A.
|
|
<strong>Report of the second international workshop on human chromosome 6.</strong>
|
|
Genomics 21: 464, 1994.
|
|
|
|
|
|
[PubMed: 8088851]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1994.1302]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
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Watase, K., Venken, K. J. T., Sun, Y., Orr, H. T., Zoghbi, H. Y.
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<strong>Regional differences of somatic CAG repeat instability do not account for selective neuronal vulnerability in a knock-in mouse model of SCA1.</strong>
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Hum. Molec. Genet. 12: 2789-2795, 2003.
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[PubMed: 12952864]
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[Full Text: https://doi.org/10.1093/hmg/ddg300]
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Yue, S., Serra, H. G., Zoghbi, H. Y., Orr, H. T.
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<strong>The spinocerebellar ataxia type 1 protein, ataxin-1, has RNA-binding activity that is inversely affected by the length of its polyglutamine tract.</strong>
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Hum. Molec. Genet. 10: 25-30, 2001.
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[PubMed: 11136710]
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[Full Text: https://doi.org/10.1093/hmg/10.1.25]
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Zuhlke, C., Dalski, A., Hellenbroich, Y., Bubel, S., Schwinger, E., Burk, K.
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<strong>Spinocerebellar ataxia type 1 (SCA1): Phenotype-genotype correlation studies in intermediate alleles.</strong>
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Europ. J. Hum. Genet. 10: 204-209, 2002.
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[PubMed: 11973625]
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[Full Text: https://doi.org/10.1038/sj.ejhg.5200788]
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Bao Lige - updated : 08/20/2018<br>Patricia A. Hartz - updated : 11/1/2013<br>Cassandra L. Kniffin - updated : 5/20/2013<br>Ada Hamosh - updated : 11/29/2011<br>Patricia A. Hartz - updated : 10/21/2011<br>Matthew B. Gross - updated : 5/7/2009<br>Patricia A. Hartz - updated : 1/14/2009<br>Ada Hamosh - updated : 5/21/2008<br>George E. Tiller - updated : 6/21/2007<br>Victor A. McKusick - updated : 4/4/2007<br>Patricia A. Hartz - updated : 8/9/2006<br>George E. Tiller - updated : 1/31/2006<br>Patricia A. Hartz - updated : 10/20/2005<br>Patricia A. Hartz - updated : 8/23/2005<br>George E. Tiller - updated : 2/17/2005<br>Victor A. McKusick - updated : 5/13/2004<br>George E. Tiller - updated : 2/12/2004<br>Dawn Watkins-Chow - updated : 12/2/2003<br>Cassandra L. Kniffin - updated : 9/22/2003<br>Stylianos E. Antonarakis - updated : 7/3/2003<br>Michael B. Petersen - updated : 11/1/2002<br>Cassandra L. Kniffin - reorganized : 8/14/2002<br>George E. Tiller - updated : 2/13/2002<br>George E. Tiller - updated : 3/15/2001<br>George E. Tiller - updated : 12/12/2000<br>Stylianos E. Antonarakis - updated : 10/8/1998<br>Stylianos E. Antonarakis - updated : 10/8/1998<br>Ethylin Wang Jabs - updated : 7/21/1997
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Victor A. McKusick : 12/5/1996
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