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Entry
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- *606350 - APRATAXIN; APTX
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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">*606350</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFamily">Gene Family</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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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/606350">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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<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=ENSG00000137074;t=ENST00000379817" 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=54840" 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=606350" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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<div 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=ENSG00000137074;t=ENST00000379817" 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_001195248,NM_001195249,NM_001195250,NM_001195251,NM_001195252,NM_001195254,NM_001368995,NM_001368996,NM_001368997,NM_001368998,NM_001368999,NM_001369000,NM_001369001,NM_001369002,NM_001369003,NM_001369004,NM_001369005,NM_001369006,NM_001370669,NM_001370670,NM_001370673,NM_175069,NM_175073,NR_036577,NR_160920,NR_160921,NR_160922,NR_160923,NR_160924,NR_160925,NR_160926,NR_160927,NR_160928,NR_160929,NR_160930,NR_160931" 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_001195248" 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=606350" 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=05892&isoform_id=05892_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/APTX" 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/7020073,12804443,28329436,29890016,31455395,31455397,31455399,31455401,31455403,31455405,31874598,32394378,32479629,32527936,32527938,32527940,32527942,32527944,32527946,32527948,32527950,32527952,32527954,32527956,32527958,32527960,32527962,34538283,34538285,34538287,34538289,34538291,34538293,34538295,34538297,48428038,80747701,85397386,112180591,119578932,119578933,119578934,119578935,119578936,119578937,119578938,119578939,193786269,305410831,305410835,307746921,334291880,1589401458,1589401477,1589401483,1589401521,1589401526,1589401542,1589401550,1589401558,1589401564,1589401568,1589401571,1589401575,1622981402,1622981405,1622981813,1622981825,1658467959,1658470131,1658472267" 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/Q7Z2E3" 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=54840" 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=ENSG00000137074;t=ENST00000379817" 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=APTX" 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=APTX" 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+54840" 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/APTX" 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:54840" 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/54840" 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=chr9&hgg_gene=ENST00000379817.7&hgg_start=32972616&hgg_end=33025120&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/aptx" 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=606350[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=606350[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/APTX/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000137074" 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=APTX" 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=APTX" 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=APTX" 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=APTX&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/PA24915" 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:15984" 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/FBgn0038704.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:1913658" 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/APTX#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:1913658" 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/54840/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=54840" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-040628-2" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:54840" 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=APTX&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> 715366004<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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606350
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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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APRATAXIN; APTX
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
|
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</span>
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</p>
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</div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
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FLJ20157
|
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
|
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=APTX" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">APTX</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/9/125?start=-3&limit=10&highlight=125">9p21.1</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr9:32972616-33025120&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'})">9:32,972,616-33,025,120</a> </span>
|
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</em>
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</strong>
|
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
|
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<br />
|
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</div>
|
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<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
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</div>
|
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<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
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<tr class="active">
|
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<th>
|
|
Location
|
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</th>
|
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<th>
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|
Phenotype
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</th>
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<th>
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|
Phenotype <br /> MIM number
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</th>
|
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<th>
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Inheritance
|
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</th>
|
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<th>
|
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Phenotype <br /> mapping key
|
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</th>
|
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</tr>
|
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</thead>
|
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<tbody>
|
|
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|
<tr>
|
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<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/9/125?start=-3&limit=10&highlight=125">
|
|
9p21.1
|
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</a>
|
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</span>
|
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</td>
|
|
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|
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<td>
|
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<span class="mim-font">
|
|
Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/208920"> 208920 </a>
|
|
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/606350" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/606350" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
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<br />
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</div>
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<p>The APTX gene encodes aprataxin, a member of the histidine triad (HIT) superfamily, members of which have nucleotide-binding and diadenosine polyphosphate hydrolase activities (<a href="#6" class="mim-tip-reference" title="Date, H., Onodera, O., Tanaka, H., Iwabuchi, K., Uekawa, K., Igarashi, S., Koike, R., Hiroi, T., Yuasa, T., Awaya, Y., Sakai, T., and 9 others. <strong>Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene.</strong> Nature Genet. 29: 184-188, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11586299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11586299</a>] [<a href="https://doi.org/10.1038/ng1001-184" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11586299">Date et al., 2001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11586299" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By positional cloning, <a href="#6" class="mim-tip-reference" title="Date, H., Onodera, O., Tanaka, H., Iwabuchi, K., Uekawa, K., Igarashi, S., Koike, R., Hiroi, T., Yuasa, T., Awaya, Y., Sakai, T., and 9 others. <strong>Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene.</strong> Nature Genet. 29: 184-188, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11586299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11586299</a>] [<a href="https://doi.org/10.1038/ng1001-184" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11586299">Date et al. (2001)</a> and <a href="#13" class="mim-tip-reference" title="Moreira, M.-C., Barbot, C., Tachi, N., Kozuka, N., Uchida, E., Gibson, T., Mendonca, P., Costa, M., Barros, J., Yanagisawa, T., Watanabe, M., Ikeda, Y., Aoki, M., Nagata, T., Coutinho, P., Sequeiros, J., Koenig, M. <strong>The gene mutated in ataxia-oculomotor apraxia 1 encodes the new HIT/Zn-finger protein aprataxin.</strong> Nature Genet. 29: 189-193, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11586300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11586300</a>] [<a href="https://doi.org/10.1038/ng1001-189" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11586300">Moreira et al. (2001)</a> identified a novel gene encoding a member of the histidine triad superfamily, which had previously been identified as FLJ20157 (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=AK000164" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">AK000164</a>), as the causative gene in ataxia-oculomotor apraxia syndrome (EAOH; <a href="/entry/208920">208920</a>). <a href="#6" class="mim-tip-reference" title="Date, H., Onodera, O., Tanaka, H., Iwabuchi, K., Uekawa, K., Igarashi, S., Koike, R., Hiroi, T., Yuasa, T., Awaya, Y., Sakai, T., and 9 others. <strong>Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene.</strong> Nature Genet. 29: 184-188, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11586299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11586299</a>] [<a href="https://doi.org/10.1038/ng1001-184" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11586299">Date et al. (2001)</a> called the gene product aprataxin, with the gene symbol APTX. Although many HIT proteins had been identified (e.g., FHIT, <a href="/entry/601153">601153</a>; HINT, <a href="/entry/601314">601314</a>), aprataxin was the first to be linked to a distinct phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11586300+11586299" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Moreira, M.-C., Barbot, C., Tachi, N., Kozuka, N., Uchida, E., Gibson, T., Mendonca, P., Costa, M., Barros, J., Yanagisawa, T., Watanabe, M., Ikeda, Y., Aoki, M., Nagata, T., Coutinho, P., Sequeiros, J., Koenig, M. <strong>The gene mutated in ataxia-oculomotor apraxia 1 encodes the new HIT/Zn-finger protein aprataxin.</strong> Nature Genet. 29: 189-193, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11586300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11586300</a>] [<a href="https://doi.org/10.1038/ng1001-189" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11586300">Moreira et al. (2001)</a> identified 2 major mRNA species of APTX resulting from alternative splicing of exon 3: a short form of 168 amino acids and the first ATG codon in exon 3, and a long form with an additional 115 nucleotides of the 5-prime portion of exon 3, resulting in the addition of another 174 amino acids (for a total of 342 amino acids) and the first codon ATG codon in exon 1. The calculated molecular mass of the long form is 39.1 kD (<a href="#17" class="mim-tip-reference" title="Sano, Y., Date, H., Igarashi, S., Onodera, O., Oyake, M., Takahashi, T., Hayashi, S., Morimatsu, M., Takahashi, H., Makifuchi, T., Fukuhara, N., Tsuji, S. <strong>Aprataxin, the causative protein for EAOH is a nuclear protein with a potential role as a DNA repair protein.</strong> Ann. Neurol. 55: 241-249, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14755728/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14755728</a>] [<a href="https://doi.org/10.1002/ana.10808" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14755728">Sano et al., 2004</a>). <a href="#13" class="mim-tip-reference" title="Moreira, M.-C., Barbot, C., Tachi, N., Kozuka, N., Uchida, E., Gibson, T., Mendonca, P., Costa, M., Barros, J., Yanagisawa, T., Watanabe, M., Ikeda, Y., Aoki, M., Nagata, T., Coutinho, P., Sequeiros, J., Koenig, M. <strong>The gene mutated in ataxia-oculomotor apraxia 1 encodes the new HIT/Zn-finger protein aprataxin.</strong> Nature Genet. 29: 189-193, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11586300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11586300</a>] [<a href="https://doi.org/10.1038/ng1001-189" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11586300">Moreira et al. (2001)</a> and <a href="#6" class="mim-tip-reference" title="Date, H., Onodera, O., Tanaka, H., Iwabuchi, K., Uekawa, K., Igarashi, S., Koike, R., Hiroi, T., Yuasa, T., Awaya, Y., Sakai, T., and 9 others. <strong>Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene.</strong> Nature Genet. 29: 184-188, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11586299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11586299</a>] [<a href="https://doi.org/10.1038/ng1001-184" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11586299">Date et al. (2001)</a> numbered mutations according to both the long and short forms of the transcript. <a href="#13" class="mim-tip-reference" title="Moreira, M.-C., Barbot, C., Tachi, N., Kozuka, N., Uchida, E., Gibson, T., Mendonca, P., Costa, M., Barros, J., Yanagisawa, T., Watanabe, M., Ikeda, Y., Aoki, M., Nagata, T., Coutinho, P., Sequeiros, J., Koenig, M. <strong>The gene mutated in ataxia-oculomotor apraxia 1 encodes the new HIT/Zn-finger protein aprataxin.</strong> Nature Genet. 29: 189-193, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11586300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11586300</a>] [<a href="https://doi.org/10.1038/ng1001-189" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11586300">Moreira et al. (2001)</a> demonstrated by RT-PCR that the APTX gene is ubiquitously expressed. The long transcript is the major form found in human cell lines, with the shorter frameshifted form present in lower amounts; liver tissue has equal amounts of the 2 transcripts. By Northern blot analysis, <a href="#6" class="mim-tip-reference" title="Date, H., Onodera, O., Tanaka, H., Iwabuchi, K., Uekawa, K., Igarashi, S., Koike, R., Hiroi, T., Yuasa, T., Awaya, Y., Sakai, T., and 9 others. <strong>Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene.</strong> Nature Genet. 29: 184-188, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11586299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11586299</a>] [<a href="https://doi.org/10.1038/ng1001-184" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11586299">Date et al. (2001)</a> demonstrated ubiquitous expression of the 2.2-kb long form and limited expression of the 1.35-kb short form. <a href="#13" class="mim-tip-reference" title="Moreira, M.-C., Barbot, C., Tachi, N., Kozuka, N., Uchida, E., Gibson, T., Mendonca, P., Costa, M., Barros, J., Yanagisawa, T., Watanabe, M., Ikeda, Y., Aoki, M., Nagata, T., Coutinho, P., Sequeiros, J., Koenig, M. <strong>The gene mutated in ataxia-oculomotor apraxia 1 encodes the new HIT/Zn-finger protein aprataxin.</strong> Nature Genet. 29: 189-193, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11586300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11586300</a>] [<a href="https://doi.org/10.1038/ng1001-189" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11586300">Moreira et al. (2001)</a> noted that the long form of aprataxin is predicted to have a nuclear localization, based on the presence of a nuclear localization signal and a putative DNA-binding site. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11586300+11586299+14755728" 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 quantitative RT-PCR, <a href="#17" class="mim-tip-reference" title="Sano, Y., Date, H., Igarashi, S., Onodera, O., Oyake, M., Takahashi, T., Hayashi, S., Morimatsu, M., Takahashi, H., Makifuchi, T., Fukuhara, N., Tsuji, S. <strong>Aprataxin, the causative protein for EAOH is a nuclear protein with a potential role as a DNA repair protein.</strong> Ann. Neurol. 55: 241-249, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14755728/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14755728</a>] [<a href="https://doi.org/10.1002/ana.10808" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14755728">Sano et al. (2004)</a> confirmed that the long form of aprataxin is the dominant tissue isoform in brain, heart, lung, kidney, liver, and trachea. They also confirmed nuclear localization of the long form. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14755728" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#6" class="mim-tip-reference" title="Date, H., Onodera, O., Tanaka, H., Iwabuchi, K., Uekawa, K., Igarashi, S., Koike, R., Hiroi, T., Yuasa, T., Awaya, Y., Sakai, T., and 9 others. <strong>Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene.</strong> Nature Genet. 29: 184-188, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11586299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11586299</a>] [<a href="https://doi.org/10.1038/ng1001-184" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11586299">Date et al. (2001)</a> showed by homology search that both forms of aprataxin have a highly conserved HIT motif (His-X-His-X-His-X-X, where X is a hydrophobic amino acid), an essential motif for HIT proteins. HIT proteins have been classified into 2 branches: the fragile HIT protein family found only in animals and fungi, and the ancient HIT nucleotide-binding protein (HINT) family that has representatives in all cellular life. Phylogenetic tree analysis showed that aprataxin is the third member of the HIT protein superfamily. The mutations found in patients with early-onset ataxia with oculomotor apraxia and hypoalbuminemia involved highly conserved amino acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11586299" 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>The APTX gene maps to chromosome 9p13.3 (<a href="#6" class="mim-tip-reference" title="Date, H., Onodera, O., Tanaka, H., Iwabuchi, K., Uekawa, K., Igarashi, S., Koike, R., Hiroi, T., Yuasa, T., Awaya, Y., Sakai, T., and 9 others. <strong>Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene.</strong> Nature Genet. 29: 184-188, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11586299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11586299</a>] [<a href="https://doi.org/10.1038/ng1001-184" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11586299">Date et al., 2001</a>; <a href="#13" class="mim-tip-reference" title="Moreira, M.-C., Barbot, C., Tachi, N., Kozuka, N., Uchida, E., Gibson, T., Mendonca, P., Costa, M., Barros, J., Yanagisawa, T., Watanabe, M., Ikeda, Y., Aoki, M., Nagata, T., Coutinho, P., Sequeiros, J., Koenig, M. <strong>The gene mutated in ataxia-oculomotor apraxia 1 encodes the new HIT/Zn-finger protein aprataxin.</strong> Nature Genet. 29: 189-193, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11586300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11586300</a>] [<a href="https://doi.org/10.1038/ng1001-189" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11586300">Moreira et al., 2001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11586300+11586299" 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="#17" class="mim-tip-reference" title="Sano, Y., Date, H., Igarashi, S., Onodera, O., Oyake, M., Takahashi, T., Hayashi, S., Morimatsu, M., Takahashi, H., Makifuchi, T., Fukuhara, N., Tsuji, S. <strong>Aprataxin, the causative protein for EAOH is a nuclear protein with a potential role as a DNA repair protein.</strong> Ann. Neurol. 55: 241-249, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14755728/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14755728</a>] [<a href="https://doi.org/10.1002/ana.10808" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14755728">Sano et al. (2004)</a> demonstrated in vitro that the long form of aprataxin, but not the short form, interacts with the C-terminal domain of the XRCC1 (<a href="/entry/194360">194360</a>) gene, suggesting that the N-terminal region of aprataxin is essential for the interaction. <a href="#17" class="mim-tip-reference" title="Sano, Y., Date, H., Igarashi, S., Onodera, O., Oyake, M., Takahashi, T., Hayashi, S., Morimatsu, M., Takahashi, H., Makifuchi, T., Fukuhara, N., Tsuji, S. <strong>Aprataxin, the causative protein for EAOH is a nuclear protein with a potential role as a DNA repair protein.</strong> Ann. Neurol. 55: 241-249, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14755728/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14755728</a>] [<a href="https://doi.org/10.1002/ana.10808" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14755728">Sano et al. (2004)</a> noted that the N terminus of the long form of aprataxin is homologous with the polynucleotide kinase 3-prime phosphatase gene (PNKP; <a href="/entry/605610">605610</a>). <a href="#21" class="mim-tip-reference" title="Whitehouse, C. J., Taylor, R. M., Thistlethwaite, A., Zhang, H., Karimi-Busheri, F., Lasko, D. D., Weinfeld, M., Caldecott, K. W. <strong>XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair.</strong> Cell 104: 107-117, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11163244/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11163244</a>] [<a href="https://doi.org/10.1016/s0092-8674(01)00195-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11163244">Whitehouse et al. (2001)</a> reported that XRCC1 interacts with PNKP in addition to its interactions with DNA polymerase-beta (POLB; <a href="/entry/174760">174760</a>) and DNA ligase III (LIG3; <a href="/entry/600940">600940</a>), forming a multiprotein complex that repairs single-strand breaks, typical of those induced by reactive oxygen species and ionizing radiation. <a href="#17" class="mim-tip-reference" title="Sano, Y., Date, H., Igarashi, S., Onodera, O., Oyake, M., Takahashi, T., Hayashi, S., Morimatsu, M., Takahashi, H., Makifuchi, T., Fukuhara, N., Tsuji, S. <strong>Aprataxin, the causative protein for EAOH is a nuclear protein with a potential role as a DNA repair protein.</strong> Ann. Neurol. 55: 241-249, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14755728/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14755728</a>] [<a href="https://doi.org/10.1002/ana.10808" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14755728">Sano et al. (2004)</a> suggested that aprataxin may be involved in this repair complex, and that accumulation of damaged DNA underlies the pathophysiologic mechanisms of EAOH. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11163244+14755728" 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="Gueven, N., Becherel, O. J., Kijas, A. W., Chen, P., Howe, O., Rudolph, J. H., Gatti, R., Date, H., Onodera, O., Taucher-Scholz, G., Lavin, M. F. <strong>Aprataxin, a novel protein that protects against genotoxic stress.</strong> Hum. Molec. Genet. 13: 1081-1093, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15044383/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15044383</a>] [<a href="https://doi.org/10.1093/hmg/ddh122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15044383">Gueven et al. (2004)</a> demonstrated that aprataxin is a nuclear protein, present in both the nucleoplasm and the nucleolus. Mutations in the APTX gene destabilized the aprataxin protein, and fusion constructs of enhanced green fluorescent protein and aprataxin, representing deletions of putative functional domains, generated highly unstable products. Cells from EAOH patients were characterized by enhanced sensitivity to agents that caused single-strand breaks in DNA, but there was no evidence for a gross defect in single-strand break repair. Sensitivity to hydrogen peroxide and the resulting genome instability were corrected by transfection with full-length aprataxin cDNA. Aprataxin interacted with the repair proteins XRCC1, PARP1 (<a href="/entry/173870">173870</a>), and p53 (<a href="/entry/191170">191170</a>) and colocalized with XRCC1 along charged particle tracks on chromatin. The authors concluded that aprataxin may influence the cellular response to genotoxic stress interacting with a number of proteins involved in DNA repair. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15044383" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Clements, P. M., Breslin, C., Deeks, E. D., Byrd, P. J., Ju, L., Bieganowski, P., Brenner, C., Moreira, M. C., Talyor, A. M., Caldecott, K. W. <strong>The ataxia-oculomotor apraxia 1 gene product has a role distinct from ATM and interacts with the DNA strand break repair proteins XRCC1 and XRCC4.</strong> DNA Repair 3: 1493-1502, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15380105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15380105</a>] [<a href="https://doi.org/10.1016/j.dnarep.2004.06.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15380105">Clements et al. (2004)</a> reported that cell lines derived from patients with ataxia-oculomotor apraxia-1 (AOA1; <a href="/entry/208920">208920</a>) exhibit neither radioresistant DNA synthesis nor a reduced ability to phosphorylate downstream targets of ATM (<a href="/entry/607585">607585</a>) following DNA damage, suggesting that AOA1 lacks the cell cycle checkpoint defects that are characteristic of ataxia telangiectasia. In addition, AOA1 primary fibroblasts exhibit only mild sensitivity to ionizing radiation, hydrogen peroxide, and methyl methanesulfonate. Strikingly, however, aprataxin physically interacts in vitro and in vivo with the DNA strand break repair proteins XRCC1 and XRCC4 (<a href="/entry/194363">194363</a>). Aprataxin possesses a divergent forkhead-associated (FHA) domain that closely resembles the FHA domain present in polynucleotide kinase (PNKP; <a href="/entry/605610">605610</a>), and appears to mediate the interactions with CK2 (see <a href="/entry/115440">115440</a>)-phosphorylated XRCC1 and XRCC4 through this domain. <a href="#4" class="mim-tip-reference" title="Clements, P. M., Breslin, C., Deeks, E. D., Byrd, P. J., Ju, L., Bieganowski, P., Brenner, C., Moreira, M. C., Talyor, A. M., Caldecott, K. W. <strong>The ataxia-oculomotor apraxia 1 gene product has a role distinct from ATM and interacts with the DNA strand break repair proteins XRCC1 and XRCC4.</strong> DNA Repair 3: 1493-1502, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15380105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15380105</a>] [<a href="https://doi.org/10.1016/j.dnarep.2004.06.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15380105">Clements et al. (2004)</a> concluded that aprataxin is therefore physically associated with both the DNA single-strand and double-strand break repair machinery, raising the possibility that AOA1 is a novel DNA damage response-defective disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15380105" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Luo, H., Chan, D. W., Yang, T., Rodriguez, M., Chen, B. P., Leng, M., Mu, J. J., Chen, D., Songyang, Z., Wang, Y., Qin, J. <strong>A new XRCC1-containing complex and its role in cellular survival of methyl methanesulfonate treatment.</strong> Molec. Cell Biol. 24: 8356-8365, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15367657/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15367657</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15367657[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1128/MCB.24.19.8356-8365.2004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15367657">Luo et al. (2004)</a> provided biochemical data to demonstrate that 2 preformed XRCC1 protein complexes exist in cycling HeLa cells. One complex contains known enzymes that are important for single-stranded break repair, including DNA ligase III (LIG3), PNKP, and polymerase-beta (<a href="/entry/174760">174760</a>); the other is a novel complex that contains LIG3 and aprataxin. <a href="#12" class="mim-tip-reference" title="Luo, H., Chan, D. W., Yang, T., Rodriguez, M., Chen, B. P., Leng, M., Mu, J. J., Chen, D., Songyang, Z., Wang, Y., Qin, J. <strong>A new XRCC1-containing complex and its role in cellular survival of methyl methanesulfonate treatment.</strong> Molec. Cell Biol. 24: 8356-8365, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15367657/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15367657</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15367657[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1128/MCB.24.19.8356-8365.2004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15367657">Luo et al. (2004)</a> characterized the new XRCC1 complex. XRCC1 is phosphorylated in vivo and in vitro by CK2, and CK2 phosphorylation of XRCC1 on ser518, thr519, and thr523 largely determines aprataxin binding to XRCC1 through its FHA domain. An acute loss of aprataxin by small interfering RNA renders HeLa cells sensitive to methyl methanesulfonate treatment by a mechanism of shortened half-life of XRCC1. Thus, <a href="#12" class="mim-tip-reference" title="Luo, H., Chan, D. W., Yang, T., Rodriguez, M., Chen, B. P., Leng, M., Mu, J. J., Chen, D., Songyang, Z., Wang, Y., Qin, J. <strong>A new XRCC1-containing complex and its role in cellular survival of methyl methanesulfonate treatment.</strong> Molec. Cell Biol. 24: 8356-8365, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15367657/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15367657</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15367657[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1128/MCB.24.19.8356-8365.2004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15367657">Luo et al. (2004)</a> concluded that aprataxin plays a role to maintain the steady-state protein level of XRCC1. <a href="#12" class="mim-tip-reference" title="Luo, H., Chan, D. W., Yang, T., Rodriguez, M., Chen, B. P., Leng, M., Mu, J. J., Chen, D., Songyang, Z., Wang, Y., Qin, J. <strong>A new XRCC1-containing complex and its role in cellular survival of methyl methanesulfonate treatment.</strong> Molec. Cell Biol. 24: 8356-8365, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15367657/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15367657</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15367657[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1128/MCB.24.19.8356-8365.2004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15367657">Luo et al. (2004)</a> concluded that collectively, their data provide insights into the single-strand break repair molecular machinery in the cell and point to involvement of aprataxin in this process, thus linking single-stranded break repair to the neurologic disease AOA1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15367657" 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>Aprataxin associates with DNA repair proteins XRCC1 and XRCC4, which are partners of DNA ligase III and ligase IV (<a href="/entry/601837">601837</a>), respectively, suggestive of a role in DNA repair. Consistent with this, APTX-defective cell lines are sensitive to agents that cause single-strand breaks and exhibit an increased incidence of induced chromosomal aberrations. Using purified aprataxin protein and extracts derived from either APTX-defective chicken DT40 cells or Aptx -/- mouse primary neural cells, <a href="#1" class="mim-tip-reference" title="Ahel, I., Rass, U., El-Khamisy, S. F., Katyal, S., Clements, P. M., McKinnon, P. J., Caldecott, K. W., West, S. C. <strong>The neurodegenerative disease protein aprataxin resolves abortive DNA ligation intermediates.</strong> Nature 443: 713-716, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16964241/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16964241</a>] [<a href="https://doi.org/10.1038/nature05164" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16964241">Ahel et al. (2006)</a> showed that aprataxin resolves abortive DNA ligation intermediates. Specifically, aprataxin catalyzes the nucleophilic release of adenylate groups covalently linked to 5-prime-phosphate termini at single-strand nicks and gaps, resulting in the production of 5-prime-phosphate termini that can be efficiently rejoined. <a href="#1" class="mim-tip-reference" title="Ahel, I., Rass, U., El-Khamisy, S. F., Katyal, S., Clements, P. M., McKinnon, P. J., Caldecott, K. W., West, S. C. <strong>The neurodegenerative disease protein aprataxin resolves abortive DNA ligation intermediates.</strong> Nature 443: 713-716, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16964241/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16964241</a>] [<a href="https://doi.org/10.1038/nature05164" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16964241">Ahel et al. (2006)</a> suggested that neurologic disorders associated with APTX mutations may be caused by the gradual accumulation of unrepaired DNA strand breaks resulting from abortive DNA ligation events. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16964241" 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="Hirano, M., Yamamoto, A., Mori, T., Lan, L., Iwamoto, T., Aoki, M., Shimada, K., Furiya, Y., Kariya, S., Asai, H., Yasui, A., Nishiwaki, T., Imoto, K., Kobayashi, N., Kiriyama, T., Nagata, T., Konishi, N., Itoyama, Y., Ueno, S. <strong>DNA single-strand break repair is impaired in aprataxin-related ataxia.</strong> Ann. Neurol. 61: 162-174, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17315206/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17315206</a>] [<a href="https://doi.org/10.1002/ana.21078" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17315206">Hirano et al. (2007)</a> demonstrated that XRCC1 and APTX accumulated to laser-induced single-strand DNA breaks and UV-induced cyclobutane pyrimidine dimers within minutes of irradiation in HeLa and Chinese hamster ovary cells. Recruitment of APTX was dependent on the presence of XRCC1. APTX mutant proteins accumulated in DNA lesions but showed impaired stability, most likely due to activation of the ubiquitin-proteasomal pathway. Fibroblasts isolated from patients with EAOH showed increased sensitivity to reactive oxygen species and decreased repair of single-strand DNA breaks compared to controls, which could be partially rescued by antioxidant treatment. Accumulated oxidative DNA damage was confirmed in EAOH cerebellar cells. The findings indicated that loss of APTX function results in impaired repair of single-strand DNA breaks and that increased reactive oxygen species contribute to the disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17315206" 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>Aprataxin has been shown to interact with PARP1, a key player in the detection of DNA single-strand breaks. <a href="#9" class="mim-tip-reference" title="Harris, J. L., Jakob, B., Taucher-Scholz, G., Dianov, G. L., Becherel, O. J., Lavin, M. F. <strong>Aprataxin, poly-ADP ribose polymerase 1 (PARP-1) and apurinic endonuclease 1 (APE1) function together to protect the genome against oxidative damage.</strong> Hum. Molec. Genet. 18: 4102-4117, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19643912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19643912</a>] [<a href="https://doi.org/10.1093/hmg/ddp359" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19643912">Harris et al. (2009)</a> reported reduced expression of PARP1, apurinic endonuclease-1 (APEX1; <a href="/entry/107748">107748</a>) and OGG1 (<a href="/entry/601982">601982</a>) in AOA1 cells and demonstrated a requirement for PARP1 in the recruitment of aprataxin to sites of DNA single-strand breaks. Mouse embryonic fibroblasts (MEFs) derived from Parp1-knockout mice showed reduced levels of aprataxin and reduced DNA-adenylate hydrolysis; however, inhibition of PARP1 activity did not affect aprataxin activity in vitro. Rather, aprataxin failed to relocalize to sites of DNA single-strand breaks in Parp1-null MEFs compared to wildtype cells, and inhibition of PARP1 activity resulted in delayed recruitment of aprataxin to DNA breaks. There were elevated levels of oxidative DNA damage in AOA1 cells coupled with reduced base excision and gap filling repair efficiencies indicative of a synergy between aprataxin, PARP1, APE1 and OGG1 in the DNA damage response. <a href="#9" class="mim-tip-reference" title="Harris, J. L., Jakob, B., Taucher-Scholz, G., Dianov, G. L., Becherel, O. J., Lavin, M. F. <strong>Aprataxin, poly-ADP ribose polymerase 1 (PARP-1) and apurinic endonuclease 1 (APE1) function together to protect the genome against oxidative damage.</strong> Hum. Molec. Genet. 18: 4102-4117, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19643912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19643912</a>] [<a href="https://doi.org/10.1093/hmg/ddp359" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19643912">Harris et al. (2009)</a> proposed both direct and indirect modulating functions for aprataxin on base excision repair. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19643912" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Tumbale, P., Williams, J. S., Schellenberg, M. J., Kunkel, T. A., Williams, R. S. <strong>Aprataxin resolves adenylated RNA-DNA junctions to maintain genome integrity.</strong> Nature 506: 111-115, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24362567/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24362567</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24362567[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/nature12824" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24362567">Tumbale et al. (2014)</a> examined the importance of APTX to RNase-H2-dependent excision repair (RER) of a lesion that is very frequently introduced into DNA, a ribonucleotide. <a href="#20" class="mim-tip-reference" title="Tumbale, P., Williams, J. S., Schellenberg, M. J., Kunkel, T. A., Williams, R. S. <strong>Aprataxin resolves adenylated RNA-DNA junctions to maintain genome integrity.</strong> Nature 506: 111-115, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24362567/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24362567</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24362567[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/nature12824" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24362567">Tumbale et al. (2014)</a> showed that ligases generate adenylated 5-prime ends containing a ribose characteristic of RNase H2 incision. APTX efficiently repairs adenylated RNA-DNA, and acting in an RNA-DNA damage response, promotes cellular survival and prevents S-phase checkpoint activation in budding yeast undergoing RER. Structure-function studies of human APTX-RNA-DNA-AMP-zinc complexes define a mechanism for detecting and reversing adenylation at RNA-DNA junctions. This involves A-form RNA binding, proper protein folding, and conformational changes, all of which are affected by heritable APTX mutations in ataxia with oculomotor apraxia-1 (<a href="/entry/208920">208920</a>). <a href="#20" class="mim-tip-reference" title="Tumbale, P., Williams, J. S., Schellenberg, M. J., Kunkel, T. A., Williams, R. S. <strong>Aprataxin resolves adenylated RNA-DNA junctions to maintain genome integrity.</strong> Nature 506: 111-115, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24362567/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24362567</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24362567[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/nature12824" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24362567">Tumbale et al. (2014)</a> concluded that accumulation of adenylated RNA-DNA may contribute to neurologic disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24362567" 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="Garcia-Diaz, B., Barca, E., Balreira, A., Lopez, L. C., Tadesse, S., Krishna, S., Naini, A., Mariotti, C., Castellotti, B., Quinzii, C. M. <strong>Lack of aprataxin impairs mitochondrial functions via downregulation of the APE1/NRF1/NRF2 pathway.</strong> Hum. Molec. Genet. 24: 4516-4529, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25976310/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25976310</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25976310[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddv183" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25976310">Garcia-Diaz et al. (2015)</a> found that most, but not all, cell lines derived from AOA1 patient fibroblasts showed coenzyme Q10 (CoQ10) deficiency due to reduced mRNA and protein expression of PDSS1 (<a href="/entry/607429">607429</a>), the first committed enzyme of CoQ10 biosynthesis. Low PDSS1 was caused by reduced activity of a transcriptional regulatory pathway that included APE1, NRF1 (<a href="/entry/600879">600879</a>), and NRF2 (see <a href="/entry/600609">600609</a>). Knockdown of APTX or APE1 in HeLa cells recapitulated CoQ10 deficiency and other mitochondrial abnormalities, and these abnormalities were reversed by upregulation of NRF2. <a href="#7" class="mim-tip-reference" title="Garcia-Diaz, B., Barca, E., Balreira, A., Lopez, L. C., Tadesse, S., Krishna, S., Naini, A., Mariotti, C., Castellotti, B., Quinzii, C. M. <strong>Lack of aprataxin impairs mitochondrial functions via downregulation of the APE1/NRF1/NRF2 pathway.</strong> Hum. Molec. Genet. 24: 4516-4529, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25976310/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25976310</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25976310[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddv183" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25976310">Garcia-Diaz et al. (2015)</a> concluded that mitochondrial dysfunction in APTX-depleted cells is not due to involvement of APTX in mtDNA repair, but rather to a role for APTX in transcriptional regulation of mitochondrial function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25976310" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#6" class="mim-tip-reference" title="Date, H., Onodera, O., Tanaka, H., Iwabuchi, K., Uekawa, K., Igarashi, S., Koike, R., Hiroi, T., Yuasa, T., Awaya, Y., Sakai, T., and 9 others. <strong>Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene.</strong> Nature Genet. 29: 184-188, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11586299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11586299</a>] [<a href="https://doi.org/10.1038/ng1001-184" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11586299">Date et al. (2001)</a> and <a href="#13" class="mim-tip-reference" title="Moreira, M.-C., Barbot, C., Tachi, N., Kozuka, N., Uchida, E., Gibson, T., Mendonca, P., Costa, M., Barros, J., Yanagisawa, T., Watanabe, M., Ikeda, Y., Aoki, M., Nagata, T., Coutinho, P., Sequeiros, J., Koenig, M. <strong>The gene mutated in ataxia-oculomotor apraxia 1 encodes the new HIT/Zn-finger protein aprataxin.</strong> Nature Genet. 29: 189-193, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11586300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11586300</a>] [<a href="https://doi.org/10.1038/ng1001-189" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11586300">Moreira et al. (2001)</a> identified mutations in the APTX gene as the cause of ataxia-oculomotor apraxia-1 (AOA1; <a href="/entry/208920">208920</a>). <a href="#6" class="mim-tip-reference" title="Date, H., Onodera, O., Tanaka, H., Iwabuchi, K., Uekawa, K., Igarashi, S., Koike, R., Hiroi, T., Yuasa, T., Awaya, Y., Sakai, T., and 9 others. <strong>Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene.</strong> Nature Genet. 29: 184-188, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11586299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11586299</a>] [<a href="https://doi.org/10.1038/ng1001-184" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11586299">Date et al. (2001)</a> observed that an insertion or deletion mutation resulted in a severe phenotype with childhood onset, whereas missense mutations resulted in a mild phenotype with relatively late age at onset; in their pedigree 2637 with compound heterozygosity for val89-to-gly (V89G; <a href="#0004">606350.0004</a>) and pro32-to-leu (P32L; <a href="#0002">606350.0002</a>), the age at onset was 25 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11586300+11586299" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Castellotti, B., Mariotti, C., Rimoldi, M., Fancellu, R., Plumari, M., Caimi, S., Uziel, G., Nardocci, N., Moroni, I., Zorzi, G., Pareyson, D., Di Bella, D., Di Donato, S., Taroni, F., Gellera, C. <strong>Ataxia with oculomotor apraxia type 1 (AOA1): novel and recurrent aprataxin mutations, coenzyme Q10 analyses, and clinical findings in Italian patients.</strong> Neurogenetics 12: 193-201, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21465257/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21465257</a>] [<a href="https://doi.org/10.1007/s10048-011-0281-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21465257">Castellotti et al. (2011)</a> identified recessive APTX mutations in 13 (6.4%) of 204 Italian probands with progressive cerebellar ataxia. The most common mutation was W279X (<a href="#0006">606350.0006</a>), which was found in homozygous state in 7 patients and in compound heterozygosity with another pathogenic APTX mutation in 1 patient. Three additional novel mutations were identified. The patients had a homogeneous phenotype consistent with AOA1. Western blot analysis of patient lymphocytes showed severely decreased levels of APTX protein, consistent with loss of function as a disease mechanism. There were no genotype/phenotype correlations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21465257" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#6" class="mim-tip-reference" title="Date, H., Onodera, O., Tanaka, H., Iwabuchi, K., Uekawa, K., Igarashi, S., Koike, R., Hiroi, T., Yuasa, T., Awaya, Y., Sakai, T., and 9 others. <strong>Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene.</strong> Nature Genet. 29: 184-188, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11586299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11586299</a>] [<a href="https://doi.org/10.1038/ng1001-184" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11586299">Date et al. (2001)</a> found that affected individuals in 3 pedigrees with EAOH (<a href="/entry/208920">208920</a>) carried a homozygous insertion of a T after nucleotide 167 (167delT; nucleotide number starting at the first ATG codon of the short form), which results in a frameshift with a premature stop. Affected individuals in these 3 families were homozygous; in 3 other pedigrees affected members had this mutation in heterozygous state in combination with a different mutation. Among their patients, <a href="#13" class="mim-tip-reference" title="Moreira, M.-C., Barbot, C., Tachi, N., Kozuka, N., Uchida, E., Gibson, T., Mendonca, P., Costa, M., Barros, J., Yanagisawa, T., Watanabe, M., Ikeda, Y., Aoki, M., Nagata, T., Coutinho, P., Sequeiros, J., Koenig, M. <strong>The gene mutated in ataxia-oculomotor apraxia 1 encodes the new HIT/Zn-finger protein aprataxin.</strong> Nature Genet. 29: 189-193, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11586300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11586300</a>] [<a href="https://doi.org/10.1038/ng1001-189" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11586300">Moreira et al. (2001)</a> found that the Japanese founding haplotypes were associated with the same mutation, which they called 689insT according to the gene's long transcript. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11586300+11586299" 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>The second most common mutation found by <a href="#6" class="mim-tip-reference" title="Date, H., Onodera, O., Tanaka, H., Iwabuchi, K., Uekawa, K., Igarashi, S., Koike, R., Hiroi, T., Yuasa, T., Awaya, Y., Sakai, T., and 9 others. <strong>Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene.</strong> Nature Genet. 29: 184-188, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11586299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11586299</a>] [<a href="https://doi.org/10.1038/ng1001-184" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11586299">Date et al. (2001)</a> in families with EAOH (<a href="/entry/208920">208920</a>) was a C-to-T transition resulting in a pro32-to-leu amino acid change. This mutation removes a proline residue that is highly conserved among all the subfamilies of HIT proteins. <a href="#13" class="mim-tip-reference" title="Moreira, M.-C., Barbot, C., Tachi, N., Kozuka, N., Uchida, E., Gibson, T., Mendonca, P., Costa, M., Barros, J., Yanagisawa, T., Watanabe, M., Ikeda, Y., Aoki, M., Nagata, T., Coutinho, P., Sequeiros, J., Koenig, M. <strong>The gene mutated in ataxia-oculomotor apraxia 1 encodes the new HIT/Zn-finger protein aprataxin.</strong> Nature Genet. 29: 189-193, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11586300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11586300</a>] [<a href="https://doi.org/10.1038/ng1001-189" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11586300">Moreira et al. (2001)</a> designated this mutation PRO206LEU according to the APTX gene's long transcript. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11586300+11586299" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 ATAXIA, EARLY-ONSET, WITH OCULOMOTOR APRAXIA AND HYPOALBUMINEMIA</strong>
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APTX, 1-BP DEL, 318T
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587776594 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776594;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=rs587776594" 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=rs587776594" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004677" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004677" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004677</a>
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<p>In one pedigree, <a href="#6" class="mim-tip-reference" title="Date, H., Onodera, O., Tanaka, H., Iwabuchi, K., Uekawa, K., Igarashi, S., Koike, R., Hiroi, T., Yuasa, T., Awaya, Y., Sakai, T., and 9 others. <strong>Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene.</strong> Nature Genet. 29: 184-188, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11586299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11586299</a>] [<a href="https://doi.org/10.1038/ng1001-184" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11586299">Date et al. (2001)</a> observed that members with EAOH (<a href="/entry/208920">208920</a>) were homozygous for a 318delT single-nucleotide deletion resulting in a frameshift with a premature stop. In 3 pedigrees, the 167insT (<a href="#0001">606350.0001</a>), P32L (<a href="#0002">606350.0002</a>), and 318delT mutations were present in compound heterozygous state. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11586299" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 ATAXIA, EARLY-ONSET, WITH OCULOMOTOR APRAXIA AND HYPOALBUMINEMIA</strong>
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APTX, VAL89GLY
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908132 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908132;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=rs121908132" 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=rs121908132" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004678" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004678" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004678</a>
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<p>In a family with EAOH (<a href="/entry/208920">208920</a>), <a href="#6" class="mim-tip-reference" title="Date, H., Onodera, O., Tanaka, H., Iwabuchi, K., Uekawa, K., Igarashi, S., Koike, R., Hiroi, T., Yuasa, T., Awaya, Y., Sakai, T., and 9 others. <strong>Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene.</strong> Nature Genet. 29: 184-188, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11586299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11586299</a>] [<a href="https://doi.org/10.1038/ng1001-184" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11586299">Date et al. (2001)</a> observed that affected members had a val89-to-gly (V89G) missense mutation involving one of the highly conserved hydrophobic amino acids of the histidine triad. As the HIT motif forms part of the phosphate binding loop, the V89G mutation probably affects the phosphate-binding activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11586299" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 ATAXIA, EARLY-ONSET, WITH OCULOMOTOR APRAXIA AND HYPOALBUMINEMIA</strong>
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APTX, HIS27ARG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908133 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908133;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=rs121908133" 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=rs121908133" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004679" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004679" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004679</a>
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<p>In a Japanese brother and sister with EAOH (<a href="/entry/208920">208920</a>) born of consanguineous parents, <a href="#18" class="mim-tip-reference" title="Shimazaki, H., Takiyama, Y., Sakoe, K., Ikeguchi, K., Niijima, K., Kaneko, J., Namekawa, M., Ogawa, T., Date, H., Tsuji, S., Nakano, I., Nishizawa, M. <strong>Early-onset ataxia with ocular motor apraxia and hypoalbuminemia: the aprataxin gene mutations.</strong> Neurology 59: 590-595, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12196655/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12196655</a>] [<a href="https://doi.org/10.1212/wnl.59.4.590" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12196655">Shimazaki et al. (2002)</a> identified a homozygous missense mutation in the aprataxin gene, an 80A-G transition which resulted in a his27-to-arg substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12196655" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0006" class="mim-anchor"></a>
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<h4>
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<strong>.0006 ATAXIA, EARLY-ONSET, WITH OCULOMOTOR APRAXIA AND HYPOALBUMINEMIA</strong>
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APTX, TRP279TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104894103 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894103;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs104894103?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894103" 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=rs104894103" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004681 OR RCV000197775 OR RCV002512761 OR RCV004757946" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004681, RCV000197775, RCV002512761, RCV004757946" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004681...</a>
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<p>In patients with EAOH (<a href="/entry/208920">208920</a>) from 5 Portuguese families, <a href="#13" class="mim-tip-reference" title="Moreira, M.-C., Barbot, C., Tachi, N., Kozuka, N., Uchida, E., Gibson, T., Mendonca, P., Costa, M., Barros, J., Yanagisawa, T., Watanabe, M., Ikeda, Y., Aoki, M., Nagata, T., Coutinho, P., Sequeiros, J., Koenig, M. <strong>The gene mutated in ataxia-oculomotor apraxia 1 encodes the new HIT/Zn-finger protein aprataxin.</strong> Nature Genet. 29: 189-193, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11586300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11586300</a>] [<a href="https://doi.org/10.1038/ng1001-189" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11586300">Moreira et al. (2001)</a> identified an 837G-A transition in exon 6 of the APTX gene, resulting in a trp279-to-ter (W279X) mutation, in association with a founding haplotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11586300" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In an Italian patient with classic EAOH, <a href="#19" class="mim-tip-reference" title="Tranchant, C., Fleury, M., Moreira, M. C., Koenig, M., Warter, J. M. <strong>Phenotypic variability of aprataxin gene mutations.</strong> Neurology 60: 868-870, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12629250/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12629250</a>] [<a href="https://doi.org/10.1212/01.wnl.0000048562.88536.a4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12629250">Tranchant et al. (2003)</a> identified homozygosity for the W279X mutation. Two French sibs were found to have compound heterozygosity for the W279X mutation and a missense mutation. Their phenotype was mild, with later onset of ataxia, no hypoalbuminemia, and no oculomotor apraxia. The authors noted the phenotypic variability and suggested that the missense mutation in the French sibs likely produced a semifunctional protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12629250" 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="Quinzii, C. M., Kattah, A. G., Naini, A., Akman, H. O., Mootha, V. K., DiMauro, S., Hirano, M. <strong>Coenzyme Q deficiency and cerebellar ataxia associated with an aprataxin mutation.</strong> Neurology 64: 539-541, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15699391/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15699391</a>] [<a href="https://doi.org/10.1212/01.WNL.0000150588.75281.58" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15699391">Quinzii et al. (2005)</a> identified a homozygous W279X mutation in 3 sibs originally reported by <a href="#14" class="mim-tip-reference" title="Musumeci, O., Naini, A., Slonim, A. E., Skavin, N., Hadjigeorgiou, G. L., Krawiecki, N., Weissman, B. M., Tsao, C.-Y., Mendell, J. R., Shanske, S., De Vivo, D. C., Hirano, M., DiMauro, S. <strong>Familial cerebellar ataxia with muscle coenzyme Q10 deficiency.</strong> Neurology 56: 849-855, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11294920/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11294920</a>] [<a href="https://doi.org/10.1212/wnl.56.7.849" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11294920">Musumeci et al. (2001)</a> as having familial cerebellar ataxia with muscle coenzyme Q10 (CoQ10) deficiency (see, e.g., COQ10D1, <a href="/entry/607426">607426</a>). All 3 patients responded well to CoQ10 supplementation. An affected cousin was heterozygous for the W279X mutation, but the authors suspected he had another mutation. Thirteen additional patients with coenzyme Q deficiency did not have APTX mutations. <a href="#15" class="mim-tip-reference" title="Quinzii, C., Naini, A., Salviati, L., Trevisson, E., Navas, P., DiMauro, S., Hirano, M. <strong>A mutation in Para-hydroxybenzoate-polyprenyl transferase (COQ2) causes primary coenzyme Q10 deficiency.</strong> Am. J. Hum. Genet. 78: 345-349, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16400613/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16400613</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16400613[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/10.1086/500092" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16400613">Quinzii et al. (2006)</a> noted that CoQ10 deficiency has been associated with 3 major clinical phenotypes and remarked that the finding of mutation in the APTX gene in these sibs supports the hypothesis that the ataxic form of CoQ10 deficiency is a genetically heterogeneous entity in which deficiency of CoQ10 can be secondary. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15699391+11294920+16400613" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Le Ber, I., Dubourg, O., Benoist, J.-F., Jardel, C., Mochel, F., Koenig, M., Brice, A., Lombes, A., Durr, A. <strong>Muscle coenzyme Q10 deficiencies in ataxia with oculomotor apraxia 1.</strong> Neurology 68: 295-297, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17242337/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17242337</a>] [<a href="https://doi.org/10.1212/01.wnl.0000252366.10731.43" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17242337">Le Ber et al. (2007)</a> found decreased muscle CoQ10 in 5 of 6 patients with AOA1. Three patients who were homozygous for the W279X mutation had the lowest values. The CoQ10 deficiency did not correlate with disease duration, severity, or other blood parameters, and mitochondrial morphology and respiratory function were normal. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17242337" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Castellotti, B., Mariotti, C., Rimoldi, M., Fancellu, R., Plumari, M., Caimi, S., Uziel, G., Nardocci, N., Moroni, I., Zorzi, G., Pareyson, D., Di Bella, D., Di Donato, S., Taroni, F., Gellera, C. <strong>Ataxia with oculomotor apraxia type 1 (AOA1): novel and recurrent aprataxin mutations, coenzyme Q10 analyses, and clinical findings in Italian patients.</strong> Neurogenetics 12: 193-201, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21465257/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21465257</a>] [<a href="https://doi.org/10.1007/s10048-011-0281-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21465257">Castellotti et al. (2011)</a> identified recessive APTX mutations in 13 (6.4%) of 204 Italian probands with progressive cerebellar ataxia. The most common mutation was W279X, which was found in homozygous state in 7 patients and in compound heterozygosity with another pathogenic APTX mutation in 1 patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21465257" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0007 ATAXIA, EARLY-ONSET, WITH OCULOMOTOR APRAXIA AND HYPOALBUMINEMIA</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004682" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004682" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004682</a>
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<p>In 2 affected members of a Tunisian family with EAOH (<a href="/entry/208920">208920</a>), <a href="#2" class="mim-tip-reference" title="Amouri, R., Moreira, M.-C., Zouari, M., El Euch, G., Barhoumi, C., Kefi, M., Belal, S., Koenig, M., Hentati, F. <strong>Aprataxin gene mutations in Tunisian families</strong> Neurology 63: 928-929, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15365154/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15365154</a>] [<a href="https://doi.org/10.1212/01.wnl.0000137044.06573.46" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15365154">Amouri et al. (2004)</a> identified a deletion of all 7 exons of the APTX gene. The patients showed typical clinical features of the disorder despite absence of the gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15365154" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0008 ATAXIA, EARLY-ONSET, WITH OCULOMOTOR APRAXIA AND HYPOALBUMINEMIA</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">rs1587330671 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1587330671;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=rs1587330671" 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=rs1587330671" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004680" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004680" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004680</a>
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<p>In affected members of 2 unrelated Tunisian families with EAOH (<a href="/entry/208920">208920</a>), <a href="#2" class="mim-tip-reference" title="Amouri, R., Moreira, M.-C., Zouari, M., El Euch, G., Barhoumi, C., Kefi, M., Belal, S., Koenig, M., Hentati, F. <strong>Aprataxin gene mutations in Tunisian families</strong> Neurology 63: 928-929, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15365154/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15365154</a>] [<a href="https://doi.org/10.1212/01.wnl.0000137044.06573.46" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15365154">Amouri et al. (2004)</a> identified a G-to-A transition at the acceptor splice site of exon 7 of the APTX gene, presumably leading to skipping of exon 7. The findings demonstrated that truncation of the terminal zinc finger domain is sufficient to cause the full clinical phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15365154" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0009 ATAXIA, ADULT-ONSET, WITH OCULOMOTOR APRAXIA</strong>
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APTX, LEU223PRO
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs267606665 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606665;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs267606665?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs267606665" 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=rs267606665" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004683" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004683" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004683</a>
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<p>In a patient with adult-onset ataxia with oculomotor apraxia (<a href="/entry/208920">208920</a>), <a href="#5" class="mim-tip-reference" title="Criscuolo, C., Mancini, P., Menchise, V., Sacca, F., De Michele, G., Banfi, S., Filla, A. <strong>Very late onset in ataxia oculomotor apraxia type I. (Letter)</strong> Ann. Neurol. 57: 777 only, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15852392/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15852392</a>] [<a href="https://doi.org/10.1002/ana.20463" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15852392">Criscuolo et al. (2005)</a> identified a homozygous 6668T-C transition in exon 5 of the APTX gene, resulting in a leu223-to-pro (L223P) substitution. The patient had onset at age 40 years of gait ataxia and dysarthria, but had normal ocular movements and normal serum albumin. The L223P mutation occurs in the middle of an alpha-helix domain and was predicted to cause some destabilization of protein folding. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15852392" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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Ahel, I., Rass, U., El-Khamisy, S. F., Katyal, S., Clements, P. M., McKinnon, P. J., Caldecott, K. W., West, S. C.
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<strong>The neurodegenerative disease protein aprataxin resolves abortive DNA ligation intermediates.</strong>
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Nature 443: 713-716, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16964241/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16964241</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16964241" 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/nature05164" target="_blank">Full Text</a>]
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Amouri, R., Moreira, M.-C., Zouari, M., El Euch, G., Barhoumi, C., Kefi, M., Belal, S., Koenig, M., Hentati, F.
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<strong>Aprataxin gene mutations in Tunisian families</strong>
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Neurology 63: 928-929, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15365154/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15365154</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15365154" 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/10.1212/01.wnl.0000137044.06573.46" target="_blank">Full Text</a>]
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Castellotti, B., Mariotti, C., Rimoldi, M., Fancellu, R., Plumari, M., Caimi, S., Uziel, G., Nardocci, N., Moroni, I., Zorzi, G., Pareyson, D., Di Bella, D., Di Donato, S., Taroni, F., Gellera, C.
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<strong>Ataxia with oculomotor apraxia type 1 (AOA1): novel and recurrent aprataxin mutations, coenzyme Q10 analyses, and clinical findings in Italian patients.</strong>
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Neurogenetics 12: 193-201, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21465257/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21465257</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21465257" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Clements, P. M., Breslin, C., Deeks, E. D., Byrd, P. J., Ju, L., Bieganowski, P., Brenner, C., Moreira, M. C., Talyor, A. M., Caldecott, K. W.
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<strong>The ataxia-oculomotor apraxia 1 gene product has a role distinct from ATM and interacts with the DNA strand break repair proteins XRCC1 and XRCC4.</strong>
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DNA Repair 3: 1493-1502, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15380105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15380105</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15380105" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.dnarep.2004.06.017" target="_blank">Full Text</a>]
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Criscuolo, C., Mancini, P., Menchise, V., Sacca, F., De Michele, G., Banfi, S., Filla, A.
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<strong>Very late onset in ataxia oculomotor apraxia type I. (Letter)</strong>
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Ann. Neurol. 57: 777 only, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15852392/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15852392</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15852392" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ana.20463" target="_blank">Full Text</a>]
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<div class="">
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<strong>Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene.</strong>
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Nature Genet. 29: 184-188, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11586299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11586299</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11586299" 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/ng1001-184" target="_blank">Full Text</a>]
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Garcia-Diaz, B., Barca, E., Balreira, A., Lopez, L. C., Tadesse, S., Krishna, S., Naini, A., Mariotti, C., Castellotti, B., Quinzii, C. M.
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<strong>Lack of aprataxin impairs mitochondrial functions via downregulation of the APE1/NRF1/NRF2 pathway.</strong>
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[<a href="https://doi.org/10.1093/hmg/ddv183" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/ddh122" target="_blank">Full Text</a>]
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</p>
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Harris, J. L., Jakob, B., Taucher-Scholz, G., Dianov, G. L., Becherel, O. J., Lavin, M. F.
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<strong>Aprataxin, poly-ADP ribose polymerase 1 (PARP-1) and apurinic endonuclease 1 (APE1) function together to protect the genome against oxidative damage.</strong>
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Hum. Molec. Genet. 18: 4102-4117, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19643912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19643912</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19643912" 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/ddp359" target="_blank">Full Text</a>]
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Hirano, M., Yamamoto, A., Mori, T., Lan, L., Iwamoto, T., Aoki, M., Shimada, K., Furiya, Y., Kariya, S., Asai, H., Yasui, A., Nishiwaki, T., Imoto, K., Kobayashi, N., Kiriyama, T., Nagata, T., Konishi, N., Itoyama, Y., Ueno, S.
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<strong>DNA single-strand break repair is impaired in aprataxin-related ataxia.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17315206/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17315206</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17315206" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ana.21078" target="_blank">Full Text</a>]
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</p>
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<p class="mim-text-font">
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<strong>Muscle coenzyme Q10 deficiencies in ataxia with oculomotor apraxia 1.</strong>
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Neurology 68: 295-297, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17242337/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17242337</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17242337" 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/10.1212/01.wnl.0000252366.10731.43" target="_blank">Full Text</a>]
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<strong>A new XRCC1-containing complex and its role in cellular survival of methyl methanesulfonate treatment.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15367657/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15367657</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15367657[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=15367657" 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/10.1128/MCB.24.19.8356-8365.2004" target="_blank">Full Text</a>]
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<a id="Moreira2001" class="mim-anchor"></a>
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Moreira, M.-C., Barbot, C., Tachi, N., Kozuka, N., Uchida, E., Gibson, T., Mendonca, P., Costa, M., Barros, J., Yanagisawa, T., Watanabe, M., Ikeda, Y., Aoki, M., Nagata, T., Coutinho, P., Sequeiros, J., Koenig, M.
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<strong>The gene mutated in ataxia-oculomotor apraxia 1 encodes the new HIT/Zn-finger protein aprataxin.</strong>
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Nature Genet. 29: 189-193, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11586300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11586300</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11586300" 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/ng1001-189" target="_blank">Full Text</a>]
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<a id="Musumeci2001" class="mim-anchor"></a>
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<div class="">
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Musumeci, O., Naini, A., Slonim, A. E., Skavin, N., Hadjigeorgiou, G. L., Krawiecki, N., Weissman, B. M., Tsao, C.-Y., Mendell, J. R., Shanske, S., De Vivo, D. C., Hirano, M., DiMauro, S.
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<strong>Familial cerebellar ataxia with muscle coenzyme Q10 deficiency.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11294920/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11294920</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11294920" 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/10.1212/wnl.56.7.849" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16400613/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16400613</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16400613[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=16400613" 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/10.1086/500092" target="_blank">Full Text</a>]
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<a id="Quinzii2005" class="mim-anchor"></a>
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<strong>Coenzyme Q deficiency and cerebellar ataxia associated with an aprataxin mutation.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15699391/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15699391</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15699391" 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/10.1212/01.WNL.0000150588.75281.58" target="_blank">Full Text</a>]
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<a id="Sano2004" class="mim-anchor"></a>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14755728/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14755728</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14755728" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ana.10808" target="_blank">Full Text</a>]
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<strong>Early-onset ataxia with ocular motor apraxia and hypoalbuminemia: the aprataxin gene mutations.</strong>
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[<a href="https://doi.org/10.1212/wnl.59.4.590" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1212/01.wnl.0000048562.88536.a4" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11163244/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11163244</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11163244" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0092-8674(01)00195-7" target="_blank">Full Text</a>]
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Patricia A. Hartz - updated : 9/23/2015
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Ada Hamosh - updated : 5/5/2014<br>Cassandra L. Kniffin - updated : 10/31/2012<br>Cassandra L. Kniffin - updated : 5/25/2012<br>George E. Tiller - updated : 10/13/2010<br>Cassandra L. Kniffin - updated : 2/4/2008<br>Cassandra L. Kniffin - updated : 10/11/2007<br>Ada Hamosh - updated : 10/24/2006<br>George E. Tiller - updated : 9/6/2006<br>Cassandra L. Kniffin - updated : 8/15/2005<br>Cassandra L. Kniffin - updated : 6/28/2005<br>Cassandra L. Kniffin - updated : 2/22/2005<br>Cassandra L. Kniffin - updated : 9/2/2003<br>Cassandra L. Kniffin - updated : 11/6/2002
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Victor A. McKusick : 10/3/2001
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mgross : 09/24/2015
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mgross : 9/23/2015<br>alopez : 5/5/2014<br>carol : 11/6/2012<br>ckniffin : 10/31/2012<br>carol : 5/25/2012<br>ckniffin : 5/23/2012<br>wwang : 10/13/2010<br>wwang : 2/19/2008<br>ckniffin : 2/4/2008<br>wwang : 10/19/2007<br>ckniffin : 10/11/2007<br>alopez : 11/6/2006<br>alopez : 11/6/2006<br>terry : 10/24/2006<br>alopez : 9/6/2006<br>mgross : 3/22/2006<br>alopez : 2/2/2006<br>alopez : 2/2/2006<br>alopez : 1/31/2006<br>wwang : 8/30/2005<br>wwang : 8/23/2005<br>ckniffin : 8/15/2005<br>carol : 7/5/2005<br>ckniffin : 6/28/2005<br>wwang : 2/25/2005<br>ckniffin : 2/22/2005<br>tkritzer : 5/27/2004<br>ckniffin : 5/21/2004<br>tkritzer : 9/10/2003<br>tkritzer : 9/8/2003<br>ckniffin : 9/2/2003<br>carol : 11/13/2002<br>ckniffin : 11/6/2002<br>alopez : 10/3/2001
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<strong>*</strong> 606350
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APRATAXIN; APTX
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<em>Alternative titles; symbols</em>
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FLJ20157
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<strong><em>HGNC Approved Gene Symbol: APTX</em></strong>
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<strong>SNOMEDCT:</strong> 715366004;
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Cytogenetic location: 9p21.1
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Genomic coordinates <span class="small">(GRCh38)</span> : 9:32,972,616-33,025,120 </span>
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<span class="small">(from NCBI)</span>
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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9p21.1
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Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia
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208920
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Autosomal recessive
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3
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<strong>TEXT</strong>
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<strong>Description</strong>
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<p>The APTX gene encodes aprataxin, a member of the histidine triad (HIT) superfamily, members of which have nucleotide-binding and diadenosine polyphosphate hydrolase activities (Date et al., 2001). </p>
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<strong>Cloning and Expression</strong>
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<p>By positional cloning, Date et al. (2001) and Moreira et al. (2001) identified a novel gene encoding a member of the histidine triad superfamily, which had previously been identified as FLJ20157 (GenBank AK000164), as the causative gene in ataxia-oculomotor apraxia syndrome (EAOH; 208920). Date et al. (2001) called the gene product aprataxin, with the gene symbol APTX. Although many HIT proteins had been identified (e.g., FHIT, 601153; HINT, 601314), aprataxin was the first to be linked to a distinct phenotype. </p><p>Moreira et al. (2001) identified 2 major mRNA species of APTX resulting from alternative splicing of exon 3: a short form of 168 amino acids and the first ATG codon in exon 3, and a long form with an additional 115 nucleotides of the 5-prime portion of exon 3, resulting in the addition of another 174 amino acids (for a total of 342 amino acids) and the first codon ATG codon in exon 1. The calculated molecular mass of the long form is 39.1 kD (Sano et al., 2004). Moreira et al. (2001) and Date et al. (2001) numbered mutations according to both the long and short forms of the transcript. Moreira et al. (2001) demonstrated by RT-PCR that the APTX gene is ubiquitously expressed. The long transcript is the major form found in human cell lines, with the shorter frameshifted form present in lower amounts; liver tissue has equal amounts of the 2 transcripts. By Northern blot analysis, Date et al. (2001) demonstrated ubiquitous expression of the 2.2-kb long form and limited expression of the 1.35-kb short form. Moreira et al. (2001) noted that the long form of aprataxin is predicted to have a nuclear localization, based on the presence of a nuclear localization signal and a putative DNA-binding site. </p><p>By quantitative RT-PCR, Sano et al. (2004) confirmed that the long form of aprataxin is the dominant tissue isoform in brain, heart, lung, kidney, liver, and trachea. They also confirmed nuclear localization of the long form. </p>
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<strong>Gene Family</strong>
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<p>Date et al. (2001) showed by homology search that both forms of aprataxin have a highly conserved HIT motif (His-X-His-X-His-X-X, where X is a hydrophobic amino acid), an essential motif for HIT proteins. HIT proteins have been classified into 2 branches: the fragile HIT protein family found only in animals and fungi, and the ancient HIT nucleotide-binding protein (HINT) family that has representatives in all cellular life. Phylogenetic tree analysis showed that aprataxin is the third member of the HIT protein superfamily. The mutations found in patients with early-onset ataxia with oculomotor apraxia and hypoalbuminemia involved highly conserved amino acids. </p>
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<strong>Mapping</strong>
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<p>The APTX gene maps to chromosome 9p13.3 (Date et al., 2001; Moreira et al., 2001). </p>
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<strong>Gene Function</strong>
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<p>Sano et al. (2004) demonstrated in vitro that the long form of aprataxin, but not the short form, interacts with the C-terminal domain of the XRCC1 (194360) gene, suggesting that the N-terminal region of aprataxin is essential for the interaction. Sano et al. (2004) noted that the N terminus of the long form of aprataxin is homologous with the polynucleotide kinase 3-prime phosphatase gene (PNKP; 605610). Whitehouse et al. (2001) reported that XRCC1 interacts with PNKP in addition to its interactions with DNA polymerase-beta (POLB; 174760) and DNA ligase III (LIG3; 600940), forming a multiprotein complex that repairs single-strand breaks, typical of those induced by reactive oxygen species and ionizing radiation. Sano et al. (2004) suggested that aprataxin may be involved in this repair complex, and that accumulation of damaged DNA underlies the pathophysiologic mechanisms of EAOH. </p><p>Gueven et al. (2004) demonstrated that aprataxin is a nuclear protein, present in both the nucleoplasm and the nucleolus. Mutations in the APTX gene destabilized the aprataxin protein, and fusion constructs of enhanced green fluorescent protein and aprataxin, representing deletions of putative functional domains, generated highly unstable products. Cells from EAOH patients were characterized by enhanced sensitivity to agents that caused single-strand breaks in DNA, but there was no evidence for a gross defect in single-strand break repair. Sensitivity to hydrogen peroxide and the resulting genome instability were corrected by transfection with full-length aprataxin cDNA. Aprataxin interacted with the repair proteins XRCC1, PARP1 (173870), and p53 (191170) and colocalized with XRCC1 along charged particle tracks on chromatin. The authors concluded that aprataxin may influence the cellular response to genotoxic stress interacting with a number of proteins involved in DNA repair. </p><p>Clements et al. (2004) reported that cell lines derived from patients with ataxia-oculomotor apraxia-1 (AOA1; 208920) exhibit neither radioresistant DNA synthesis nor a reduced ability to phosphorylate downstream targets of ATM (607585) following DNA damage, suggesting that AOA1 lacks the cell cycle checkpoint defects that are characteristic of ataxia telangiectasia. In addition, AOA1 primary fibroblasts exhibit only mild sensitivity to ionizing radiation, hydrogen peroxide, and methyl methanesulfonate. Strikingly, however, aprataxin physically interacts in vitro and in vivo with the DNA strand break repair proteins XRCC1 and XRCC4 (194363). Aprataxin possesses a divergent forkhead-associated (FHA) domain that closely resembles the FHA domain present in polynucleotide kinase (PNKP; 605610), and appears to mediate the interactions with CK2 (see 115440)-phosphorylated XRCC1 and XRCC4 through this domain. Clements et al. (2004) concluded that aprataxin is therefore physically associated with both the DNA single-strand and double-strand break repair machinery, raising the possibility that AOA1 is a novel DNA damage response-defective disease. </p><p>Luo et al. (2004) provided biochemical data to demonstrate that 2 preformed XRCC1 protein complexes exist in cycling HeLa cells. One complex contains known enzymes that are important for single-stranded break repair, including DNA ligase III (LIG3), PNKP, and polymerase-beta (174760); the other is a novel complex that contains LIG3 and aprataxin. Luo et al. (2004) characterized the new XRCC1 complex. XRCC1 is phosphorylated in vivo and in vitro by CK2, and CK2 phosphorylation of XRCC1 on ser518, thr519, and thr523 largely determines aprataxin binding to XRCC1 through its FHA domain. An acute loss of aprataxin by small interfering RNA renders HeLa cells sensitive to methyl methanesulfonate treatment by a mechanism of shortened half-life of XRCC1. Thus, Luo et al. (2004) concluded that aprataxin plays a role to maintain the steady-state protein level of XRCC1. Luo et al. (2004) concluded that collectively, their data provide insights into the single-strand break repair molecular machinery in the cell and point to involvement of aprataxin in this process, thus linking single-stranded break repair to the neurologic disease AOA1. </p><p>Aprataxin associates with DNA repair proteins XRCC1 and XRCC4, which are partners of DNA ligase III and ligase IV (601837), respectively, suggestive of a role in DNA repair. Consistent with this, APTX-defective cell lines are sensitive to agents that cause single-strand breaks and exhibit an increased incidence of induced chromosomal aberrations. Using purified aprataxin protein and extracts derived from either APTX-defective chicken DT40 cells or Aptx -/- mouse primary neural cells, Ahel et al. (2006) showed that aprataxin resolves abortive DNA ligation intermediates. Specifically, aprataxin catalyzes the nucleophilic release of adenylate groups covalently linked to 5-prime-phosphate termini at single-strand nicks and gaps, resulting in the production of 5-prime-phosphate termini that can be efficiently rejoined. Ahel et al. (2006) suggested that neurologic disorders associated with APTX mutations may be caused by the gradual accumulation of unrepaired DNA strand breaks resulting from abortive DNA ligation events. </p><p>Hirano et al. (2007) demonstrated that XRCC1 and APTX accumulated to laser-induced single-strand DNA breaks and UV-induced cyclobutane pyrimidine dimers within minutes of irradiation in HeLa and Chinese hamster ovary cells. Recruitment of APTX was dependent on the presence of XRCC1. APTX mutant proteins accumulated in DNA lesions but showed impaired stability, most likely due to activation of the ubiquitin-proteasomal pathway. Fibroblasts isolated from patients with EAOH showed increased sensitivity to reactive oxygen species and decreased repair of single-strand DNA breaks compared to controls, which could be partially rescued by antioxidant treatment. Accumulated oxidative DNA damage was confirmed in EAOH cerebellar cells. The findings indicated that loss of APTX function results in impaired repair of single-strand DNA breaks and that increased reactive oxygen species contribute to the disease. </p><p>Aprataxin has been shown to interact with PARP1, a key player in the detection of DNA single-strand breaks. Harris et al. (2009) reported reduced expression of PARP1, apurinic endonuclease-1 (APEX1; 107748) and OGG1 (601982) in AOA1 cells and demonstrated a requirement for PARP1 in the recruitment of aprataxin to sites of DNA single-strand breaks. Mouse embryonic fibroblasts (MEFs) derived from Parp1-knockout mice showed reduced levels of aprataxin and reduced DNA-adenylate hydrolysis; however, inhibition of PARP1 activity did not affect aprataxin activity in vitro. Rather, aprataxin failed to relocalize to sites of DNA single-strand breaks in Parp1-null MEFs compared to wildtype cells, and inhibition of PARP1 activity resulted in delayed recruitment of aprataxin to DNA breaks. There were elevated levels of oxidative DNA damage in AOA1 cells coupled with reduced base excision and gap filling repair efficiencies indicative of a synergy between aprataxin, PARP1, APE1 and OGG1 in the DNA damage response. Harris et al. (2009) proposed both direct and indirect modulating functions for aprataxin on base excision repair. </p><p>Tumbale et al. (2014) examined the importance of APTX to RNase-H2-dependent excision repair (RER) of a lesion that is very frequently introduced into DNA, a ribonucleotide. Tumbale et al. (2014) showed that ligases generate adenylated 5-prime ends containing a ribose characteristic of RNase H2 incision. APTX efficiently repairs adenylated RNA-DNA, and acting in an RNA-DNA damage response, promotes cellular survival and prevents S-phase checkpoint activation in budding yeast undergoing RER. Structure-function studies of human APTX-RNA-DNA-AMP-zinc complexes define a mechanism for detecting and reversing adenylation at RNA-DNA junctions. This involves A-form RNA binding, proper protein folding, and conformational changes, all of which are affected by heritable APTX mutations in ataxia with oculomotor apraxia-1 (208920). Tumbale et al. (2014) concluded that accumulation of adenylated RNA-DNA may contribute to neurologic disease. </p><p>Garcia-Diaz et al. (2015) found that most, but not all, cell lines derived from AOA1 patient fibroblasts showed coenzyme Q10 (CoQ10) deficiency due to reduced mRNA and protein expression of PDSS1 (607429), the first committed enzyme of CoQ10 biosynthesis. Low PDSS1 was caused by reduced activity of a transcriptional regulatory pathway that included APE1, NRF1 (600879), and NRF2 (see 600609). Knockdown of APTX or APE1 in HeLa cells recapitulated CoQ10 deficiency and other mitochondrial abnormalities, and these abnormalities were reversed by upregulation of NRF2. Garcia-Diaz et al. (2015) concluded that mitochondrial dysfunction in APTX-depleted cells is not due to involvement of APTX in mtDNA repair, but rather to a role for APTX in transcriptional regulation of mitochondrial function. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Date et al. (2001) and Moreira et al. (2001) identified mutations in the APTX gene as the cause of ataxia-oculomotor apraxia-1 (AOA1; 208920). Date et al. (2001) observed that an insertion or deletion mutation resulted in a severe phenotype with childhood onset, whereas missense mutations resulted in a mild phenotype with relatively late age at onset; in their pedigree 2637 with compound heterozygosity for val89-to-gly (V89G; 606350.0004) and pro32-to-leu (P32L; 606350.0002), the age at onset was 25 years. </p><p>Castellotti et al. (2011) identified recessive APTX mutations in 13 (6.4%) of 204 Italian probands with progressive cerebellar ataxia. The most common mutation was W279X (606350.0006), which was found in homozygous state in 7 patients and in compound heterozygosity with another pathogenic APTX mutation in 1 patient. Three additional novel mutations were identified. The patients had a homogeneous phenotype consistent with AOA1. Western blot analysis of patient lymphocytes showed severely decreased levels of APTX protein, consistent with loss of function as a disease mechanism. There were no genotype/phenotype correlations. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>9 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 ATAXIA, EARLY-ONSET, WITH OCULOMOTOR APRAXIA AND HYPOALBUMINEMIA</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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APTX, 1-BP INS, 167T
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<br />
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SNP: rs587776593,
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ClinVar: RCV000004675, RCV002512760
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>Date et al. (2001) found that affected individuals in 3 pedigrees with EAOH (208920) carried a homozygous insertion of a T after nucleotide 167 (167delT; nucleotide number starting at the first ATG codon of the short form), which results in a frameshift with a premature stop. Affected individuals in these 3 families were homozygous; in 3 other pedigrees affected members had this mutation in heterozygous state in combination with a different mutation. Among their patients, Moreira et al. (2001) found that the Japanese founding haplotypes were associated with the same mutation, which they called 689insT according to the gene's long transcript. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 ATAXIA, EARLY-ONSET, WITH OCULOMOTOR APRAXIA AND HYPOALBUMINEMIA</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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APTX, PRO32LEU
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<br />
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SNP: rs121908131,
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gnomAD: rs121908131,
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ClinVar: RCV000004676
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>The second most common mutation found by Date et al. (2001) in families with EAOH (208920) was a C-to-T transition resulting in a pro32-to-leu amino acid change. This mutation removes a proline residue that is highly conserved among all the subfamilies of HIT proteins. Moreira et al. (2001) designated this mutation PRO206LEU according to the APTX gene's long transcript. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 ATAXIA, EARLY-ONSET, WITH OCULOMOTOR APRAXIA AND HYPOALBUMINEMIA</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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APTX, 1-BP DEL, 318T
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<br />
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SNP: rs587776594,
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ClinVar: RCV000004677
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In one pedigree, Date et al. (2001) observed that members with EAOH (208920) were homozygous for a 318delT single-nucleotide deletion resulting in a frameshift with a premature stop. In 3 pedigrees, the 167insT (606350.0001), P32L (606350.0002), and 318delT mutations were present in compound heterozygous state. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0004 ATAXIA, EARLY-ONSET, WITH OCULOMOTOR APRAXIA AND HYPOALBUMINEMIA</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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APTX, VAL89GLY
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<br />
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SNP: rs121908132,
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ClinVar: RCV000004678
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a family with EAOH (208920), Date et al. (2001) observed that affected members had a val89-to-gly (V89G) missense mutation involving one of the highly conserved hydrophobic amino acids of the histidine triad. As the HIT motif forms part of the phosphate binding loop, the V89G mutation probably affects the phosphate-binding activity. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0005 ATAXIA, EARLY-ONSET, WITH OCULOMOTOR APRAXIA AND HYPOALBUMINEMIA</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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APTX, HIS27ARG
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<br />
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SNP: rs121908133,
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ClinVar: RCV000004679
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese brother and sister with EAOH (208920) born of consanguineous parents, Shimazaki et al. (2002) identified a homozygous missense mutation in the aprataxin gene, an 80A-G transition which resulted in a his27-to-arg substitution. </p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 ATAXIA, EARLY-ONSET, WITH OCULOMOTOR APRAXIA AND HYPOALBUMINEMIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
APTX, TRP279TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894103,
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|
|
|
|
|
gnomAD: rs104894103,
|
|
|
|
|
|
ClinVar: RCV000004681, RCV000197775, RCV002512761, RCV004757946
|
|
|
|
|
|
</span>
|
|
</div>
|
|
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|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In patients with EAOH (208920) from 5 Portuguese families, Moreira et al. (2001) identified an 837G-A transition in exon 6 of the APTX gene, resulting in a trp279-to-ter (W279X) mutation, in association with a founding haplotype. </p><p>In an Italian patient with classic EAOH, Tranchant et al. (2003) identified homozygosity for the W279X mutation. Two French sibs were found to have compound heterozygosity for the W279X mutation and a missense mutation. Their phenotype was mild, with later onset of ataxia, no hypoalbuminemia, and no oculomotor apraxia. The authors noted the phenotypic variability and suggested that the missense mutation in the French sibs likely produced a semifunctional protein. </p><p>Quinzii et al. (2005) identified a homozygous W279X mutation in 3 sibs originally reported by Musumeci et al. (2001) as having familial cerebellar ataxia with muscle coenzyme Q10 (CoQ10) deficiency (see, e.g., COQ10D1, 607426). All 3 patients responded well to CoQ10 supplementation. An affected cousin was heterozygous for the W279X mutation, but the authors suspected he had another mutation. Thirteen additional patients with coenzyme Q deficiency did not have APTX mutations. Quinzii et al. (2006) noted that CoQ10 deficiency has been associated with 3 major clinical phenotypes and remarked that the finding of mutation in the APTX gene in these sibs supports the hypothesis that the ataxic form of CoQ10 deficiency is a genetically heterogeneous entity in which deficiency of CoQ10 can be secondary. </p><p>Le Ber et al. (2007) found decreased muscle CoQ10 in 5 of 6 patients with AOA1. Three patients who were homozygous for the W279X mutation had the lowest values. The CoQ10 deficiency did not correlate with disease duration, severity, or other blood parameters, and mitochondrial morphology and respiratory function were normal. </p><p>Castellotti et al. (2011) identified recessive APTX mutations in 13 (6.4%) of 204 Italian probands with progressive cerebellar ataxia. The most common mutation was W279X, which was found in homozygous state in 7 patients and in compound heterozygosity with another pathogenic APTX mutation in 1 patient. </p>
|
|
</span>
|
|
</div>
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<div>
|
|
<br />
|
|
</div>
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|
|
</div>
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|
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 ATAXIA, EARLY-ONSET, WITH OCULOMOTOR APRAXIA AND HYPOALBUMINEMIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
APTX, DEL
|
|
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|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000004682
|
|
|
|
|
|
</span>
|
|
</div>
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 affected members of a Tunisian family with EAOH (208920), Amouri et al. (2004) identified a deletion of all 7 exons of the APTX gene. The patients showed typical clinical features of the disorder despite absence of the gene. </p>
|
|
</span>
|
|
</div>
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<div>
|
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<br />
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</div>
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</div>
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<div>
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 ATAXIA, EARLY-ONSET, WITH OCULOMOTOR APRAXIA AND HYPOALBUMINEMIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
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|
|
APTX, IVS7AS, G-A, -1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1587330671,
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|
|
|
|
|
|
|
ClinVar: RCV000004680
|
|
|
|
|
|
</span>
|
|
</div>
|
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|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of 2 unrelated Tunisian families with EAOH (208920), Amouri et al. (2004) identified a G-to-A transition at the acceptor splice site of exon 7 of the APTX gene, presumably leading to skipping of exon 7. The findings demonstrated that truncation of the terminal zinc finger domain is sufficient to cause the full clinical phenotype. </p>
|
|
</span>
|
|
</div>
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<div>
|
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 ATAXIA, ADULT-ONSET, WITH OCULOMOTOR APRAXIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
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|
|
APTX, LEU223PRO
|
|
|
|
|
|
<br />
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|
|
SNP: rs267606665,
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|
|
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gnomAD: rs267606665,
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|
|
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ClinVar: RCV000004683
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|
|
|
|
|
</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with adult-onset ataxia with oculomotor apraxia (208920), Criscuolo et al. (2005) identified a homozygous 6668T-C transition in exon 5 of the APTX gene, resulting in a leu223-to-pro (L223P) substitution. The patient had onset at age 40 years of gait ataxia and dysarthria, but had normal ocular movements and normal serum albumin. The L223P mutation occurs in the middle of an alpha-helix domain and was predicted to cause some destabilization of protein folding. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
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</h4>
|
|
<div>
|
|
<p />
|
|
</div>
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<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ahel, I., Rass, U., El-Khamisy, S. F., Katyal, S., Clements, P. M., McKinnon, P. J., Caldecott, K. W., West, S. C.
|
|
<strong>The neurodegenerative disease protein aprataxin resolves abortive DNA ligation intermediates.</strong>
|
|
Nature 443: 713-716, 2006.
|
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|
|
[PubMed: 16964241]
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|
|
[Full Text: https://doi.org/10.1038/nature05164]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Amouri, R., Moreira, M.-C., Zouari, M., El Euch, G., Barhoumi, C., Kefi, M., Belal, S., Koenig, M., Hentati, F.
|
|
<strong>Aprataxin gene mutations in Tunisian families</strong>
|
|
Neurology 63: 928-929, 2004.
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|
|
[PubMed: 15365154]
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|
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[Full Text: https://doi.org/10.1212/01.wnl.0000137044.06573.46]
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Castellotti, B., Mariotti, C., Rimoldi, M., Fancellu, R., Plumari, M., Caimi, S., Uziel, G., Nardocci, N., Moroni, I., Zorzi, G., Pareyson, D., Di Bella, D., Di Donato, S., Taroni, F., Gellera, C.
|
|
<strong>Ataxia with oculomotor apraxia type 1 (AOA1): novel and recurrent aprataxin mutations, coenzyme Q10 analyses, and clinical findings in Italian patients.</strong>
|
|
Neurogenetics 12: 193-201, 2011.
|
|
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|
|
[PubMed: 21465257]
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|
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[Full Text: https://doi.org/10.1007/s10048-011-0281-x]
|
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
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Clements, P. M., Breslin, C., Deeks, E. D., Byrd, P. J., Ju, L., Bieganowski, P., Brenner, C., Moreira, M. C., Talyor, A. M., Caldecott, K. W.
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<strong>The ataxia-oculomotor apraxia 1 gene product has a role distinct from ATM and interacts with the DNA strand break repair proteins XRCC1 and XRCC4.</strong>
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DNA Repair 3: 1493-1502, 2004.
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[Full Text: https://doi.org/10.1016/j.dnarep.2004.06.017]
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Criscuolo, C., Mancini, P., Menchise, V., Sacca, F., De Michele, G., Banfi, S., Filla, A.
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<strong>Very late onset in ataxia oculomotor apraxia type I. (Letter)</strong>
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Date, H., Onodera, O., Tanaka, H., Iwabuchi, K., Uekawa, K., Igarashi, S., Koike, R., Hiroi, T., Yuasa, T., Awaya, Y., Sakai, T., and 9 others.
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<strong>Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene.</strong>
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Nature Genet. 29: 184-188, 2001.
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[PubMed: 11586299]
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[Full Text: https://doi.org/10.1038/ng1001-184]
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</p>
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Garcia-Diaz, B., Barca, E., Balreira, A., Lopez, L. C., Tadesse, S., Krishna, S., Naini, A., Mariotti, C., Castellotti, B., Quinzii, C. M.
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<strong>Lack of aprataxin impairs mitochondrial functions via downregulation of the APE1/NRF1/NRF2 pathway.</strong>
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[PubMed: 25976310]
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Gueven, N., Becherel, O. J., Kijas, A. W., Chen, P., Howe, O., Rudolph, J. H., Gatti, R., Date, H., Onodera, O., Taucher-Scholz, G., Lavin, M. F.
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<strong>Aprataxin, a novel protein that protects against genotoxic stress.</strong>
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[PubMed: 15044383]
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Harris, J. L., Jakob, B., Taucher-Scholz, G., Dianov, G. L., Becherel, O. J., Lavin, M. F.
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<strong>Aprataxin, poly-ADP ribose polymerase 1 (PARP-1) and apurinic endonuclease 1 (APE1) function together to protect the genome against oxidative damage.</strong>
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Hum. Molec. Genet. 18: 4102-4117, 2009.
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[PubMed: 19643912]
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Hirano, M., Yamamoto, A., Mori, T., Lan, L., Iwamoto, T., Aoki, M., Shimada, K., Furiya, Y., Kariya, S., Asai, H., Yasui, A., Nishiwaki, T., Imoto, K., Kobayashi, N., Kiriyama, T., Nagata, T., Konishi, N., Itoyama, Y., Ueno, S.
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<strong>DNA single-strand break repair is impaired in aprataxin-related ataxia.</strong>
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Le Ber, I., Dubourg, O., Benoist, J.-F., Jardel, C., Mochel, F., Koenig, M., Brice, A., Lombes, A., Durr, A.
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<strong>Muscle coenzyme Q10 deficiencies in ataxia with oculomotor apraxia 1.</strong>
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Neurology 68: 295-297, 2007.
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[PubMed: 17242337]
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Luo, H., Chan, D. W., Yang, T., Rodriguez, M., Chen, B. P., Leng, M., Mu, J. J., Chen, D., Songyang, Z., Wang, Y., Qin, J.
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<strong>A new XRCC1-containing complex and its role in cellular survival of methyl methanesulfonate treatment.</strong>
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[PubMed: 15367657]
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Moreira, M.-C., Barbot, C., Tachi, N., Kozuka, N., Uchida, E., Gibson, T., Mendonca, P., Costa, M., Barros, J., Yanagisawa, T., Watanabe, M., Ikeda, Y., Aoki, M., Nagata, T., Coutinho, P., Sequeiros, J., Koenig, M.
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<strong>The gene mutated in ataxia-oculomotor apraxia 1 encodes the new HIT/Zn-finger protein aprataxin.</strong>
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Nature Genet. 29: 189-193, 2001.
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[PubMed: 11586300]
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Musumeci, O., Naini, A., Slonim, A. E., Skavin, N., Hadjigeorgiou, G. L., Krawiecki, N., Weissman, B. M., Tsao, C.-Y., Mendell, J. R., Shanske, S., De Vivo, D. C., Hirano, M., DiMauro, S.
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<strong>Familial cerebellar ataxia with muscle coenzyme Q10 deficiency.</strong>
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Neurology 56: 849-855, 2001.
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[PubMed: 11294920]
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Quinzii, C., Naini, A., Salviati, L., Trevisson, E., Navas, P., DiMauro, S., Hirano, M.
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<strong>A mutation in Para-hydroxybenzoate-polyprenyl transferase (COQ2) causes primary coenzyme Q10 deficiency.</strong>
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Am. J. Hum. Genet. 78: 345-349, 2006.
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[PubMed: 16400613]
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Quinzii, C. M., Kattah, A. G., Naini, A., Akman, H. O., Mootha, V. K., DiMauro, S., Hirano, M.
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<strong>Coenzyme Q deficiency and cerebellar ataxia associated with an aprataxin mutation.</strong>
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Neurology 64: 539-541, 2005.
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[PubMed: 15699391]
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Sano, Y., Date, H., Igarashi, S., Onodera, O., Oyake, M., Takahashi, T., Hayashi, S., Morimatsu, M., Takahashi, H., Makifuchi, T., Fukuhara, N., Tsuji, S.
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<strong>Aprataxin, the causative protein for EAOH is a nuclear protein with a potential role as a DNA repair protein.</strong>
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Ann. Neurol. 55: 241-249, 2004.
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[PubMed: 14755728]
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<strong>Early-onset ataxia with ocular motor apraxia and hypoalbuminemia: the aprataxin gene mutations.</strong>
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Tumbale, P., Williams, J. S., Schellenberg, M. J., Kunkel, T. A., Williams, R. S.
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<strong>Aprataxin resolves adenylated RNA-DNA junctions to maintain genome integrity.</strong>
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Nature 506: 111-115, 2014.
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Whitehouse, C. J., Taylor, R. M., Thistlethwaite, A., Zhang, H., Karimi-Busheri, F., Lasko, D. D., Weinfeld, M., Caldecott, K. W.
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<strong>XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair.</strong>
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<button type="button" id="mimDonationPopupDonate" class="btn btn-success btn-block" data-dismiss="modal"> Donate To OMIM! </button>
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</div>
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</div>
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</div>
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</div>
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</div>
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</body>
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</html>
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