3217 lines
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Entry
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- *605955 - NK6 HOMEOBOX 2; NKX6-2
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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">*605955</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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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/605955">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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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-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="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=ENSG00000148826;t=ENST00000368592" 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=84504" 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=605955" 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 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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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000148826;t=ENST00000368592" 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_177400" 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_177400" 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=605955" 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=09336&isoform_id=09336_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/NKX6-2" 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/13160477,75517780,85396895,119581712,158564033,1519312790,2462521445" 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/Q9C056" 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=84504" 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=ENSG00000148826;t=ENST00000368592" 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=NKX6-2" 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=NKX6-2" 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+84504" 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/NKX6-2" 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:84504" 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/84504" 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=chr10&hgg_gene=ENST00000368592.8&hgg_start=132783181&hgg_end=132786147&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><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=605955[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</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=605955[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/NKX6-2/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/ENSG00000148826" 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=NKX6-2" 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=NKX6-2" 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=NKX6-2" 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=NKX6-2&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/PA134896334" 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:19321" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1352738" 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/NKX6-2#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:1352738" 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/84504/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=84504" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00000584;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-070626-1" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://reactome.org/content/query?q=NKX6-2&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> 1217379007<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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605955
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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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NK6 HOMEOBOX 2; NKX6-2
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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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NK6, DROSOPHILA, HOMOLOG OF, 2<br />
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HOMEOBOX 6B, NK<br />
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NK HOMEOBOX, FAMILY 6, MEMBER B; NKX6B<br />
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NKX6.2, MOUSE, HOMOLOG OF
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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=NKX6-2" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">NKX6-2</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/10/669?start=-3&limit=10&highlight=669">10q26.3</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr10:132783181-132786147&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'})">10:132,783,181-132,786,147</a> </span>
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</em>
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</strong>
|
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="geneMap" class="mim-anchor"></a>
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<div style="margin-bottom: 10px;">
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<span class="h4 mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
|
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<a href="/geneMap/10/669?start=-3&limit=10&highlight=669">
|
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10q26.3
|
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy
|
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</span>
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</td>
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<td>
|
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<span class="mim-font">
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<a href="/entry/617560"> 617560 </a>
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</span>
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</td>
|
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal 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">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/605955" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/605955" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
|
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
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<strong>TEXT</strong>
|
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</span>
|
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</span>
|
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</h4>
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<div>
|
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<a id="description" class="mim-anchor"></a>
|
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
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<span class="mim-font">
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<strong>Description</strong>
|
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</span>
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</h4>
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</div>
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<div id="mimDescriptionFold" class="collapse in ">
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<p>The NKX6-2 gene encodes a member of the NKX protein family of transcription factors, which have established roles during the development of an organism (summary by <a href="#1" class="mim-tip-reference" title="Chelban, V., Patel, N., Vandrovcova, J., Zanetti, M. N., Lynch, D. S., Ryten, M., Botia, J. A., Bello, O., Tribollet, E., Efthymiou, S., Davagnanam, I., SYNAPSE Study Group, Bashiri, F. A., Wood, N. W., Rothman, J. E., Alkuraya, F. S., Houlden, H. <strong>Mutations in NKX6-2 cause progressive spastic ataxia and hypomyelination.</strong> Am. J. Hum. Genet. 100: 969-977, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28575651/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28575651</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28575651[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2017.05.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28575651">Chelban et al., 2017</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28575651" 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>Homeobox genes act as master genes that control pattern formation and positional information during embryonic development. In the adult, they are thought to maintain the differentiated states of cell populations and to direct the renewal of specific cell types. While homeobox genes are widely expressed in the developing vertebrate nervous system, only a few, including NKX6B, continue to be expressed in the adult brain (summary by <a href="#4" class="mim-tip-reference" title="Lee, S.-H., Davison, J. A., Vidal, S. M., Belouchi, A. <strong>Cloning, expression and chromosomal location of NKX6B to 10q26, a region frequently deleted in brain tumors.</strong> Mammalian Genome 12: 157-162, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11210186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11210186</a>] [<a href="https://doi.org/10.1007/s003350010247" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11210186">Lee et al., 2001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11210186" 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>Nkx6.2 was isolated in mouse by <a href="#3" class="mim-tip-reference" title="Komuro, I., Schalling, M., Jahn, L., Bodmer, R., Jenkins, N. A., Copeland, G. A., Izumo, S. <strong>Gtx: a novel murine homeobox-containing gene, expressed specifically in glial cells of the brain and germ cells of testis, has a transcriptional repressor activity in vitro for a serum-inducible promoter.</strong> EMBO J. 12: 1387-1401, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8096811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8096811</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1993.tb05783.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8096811">Komuro et al. (1993)</a>. Expression of Nkx6.2 appeared to be tissue specific and developmentally regulated. In day-18 mouse embryos, it was expressed in part of the forebrain as well as in mid- and hindbrain, whereas in the adult CNS, expression was most abundant in areas rich in oligodendrocyte cell bodies and astrocytes. Together with DNA binding assays, these expression studies suggested that the Nkx6.2 gene product may be important for differentiated oligodendrocyte function and in the regulation of myelin gene expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8096811" 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="Lee, S.-H., Davison, J. A., Vidal, S. M., Belouchi, A. <strong>Cloning, expression and chromosomal location of NKX6B to 10q26, a region frequently deleted in brain tumors.</strong> Mammalian Genome 12: 157-162, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11210186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11210186</a>] [<a href="https://doi.org/10.1007/s003350010247" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11210186">Lee et al. (2001)</a> cloned and characterized NKX6B, the human homolog of mouse Nkx6.2. The predicted 277-amino acid NKX6B protein shares 97% identity with mouse Nkx6.2 and 52% homology with NKX6A (NKX6-1; <a href="/entry/602563">602563</a>). Northern blot analysis showed that NKX6B expression is tightly controlled in a tissue-specific fashion, with highest expression in brain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11210186" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using immunohistochemistry and in situ hybridization, <a href="#6" class="mim-tip-reference" title="Vallstedt, A., Muhr, J., Pattyn, A., Pierani, A., Mendelsohn, M., Sander, M., Jessell, T. M., Ericson, J. <strong>Different levels of repressor activity assign redundant and specific roles to Nkx6 genes in motor neuron and interneuron specification.</strong> Neuron 31: 743-755, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11567614/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11567614</a>] [<a href="https://doi.org/10.1016/s0896-6273(01)00412-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11567614">Vallstedt et al. (2001)</a> detected expression of Nkx6-2 first in the caudal neural tube in a broad ventral domain at approximately embryonic day 8.5. Nkx6-2 was expressed predominantly within the dorsal progenitor p1 domain and more weakly in the p0 domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11567614" 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 embryonic mice, <a href="#5" class="mim-tip-reference" title="Southwood, C., He, C., Garbern, J., Kamholz, J., Arroyo, E., Gow, A. <strong>CNS myelin paranodes require Nkx6-2 homeoprotein transcriptional activity for normal structure.</strong> J. Neurosci. 24: 11215-11225, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15601927/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15601927</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15601927[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/10.1523/JNEUROSCI.3479-04.2004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15601927">Southwood et al. (2004)</a> found expression of Nkx6-2 in cranial nerves, interneuron precursors, and motoneurons that extend axons into the periphery. Nkx6-2 continued to be expressed in the nucleus of oligodendrocytes in adult mouse brain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15601927" 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 DNA sequence analysis of an 11-kb genomic fragment, <a href="#4" class="mim-tip-reference" title="Lee, S.-H., Davison, J. A., Vidal, S. M., Belouchi, A. <strong>Cloning, expression and chromosomal location of NKX6B to 10q26, a region frequently deleted in brain tumors.</strong> Mammalian Genome 12: 157-162, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11210186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11210186</a>] [<a href="https://doi.org/10.1007/s003350010247" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11210186">Lee et al. (2001)</a> demonstrated that the NKX6B gene spans 1.2 kb and contains 3 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11210186" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using STS content mapping and radiation hybrid analysis, <a href="#4" class="mim-tip-reference" title="Lee, S.-H., Davison, J. A., Vidal, S. M., Belouchi, A. <strong>Cloning, expression and chromosomal location of NKX6B to 10q26, a region frequently deleted in brain tumors.</strong> Mammalian Genome 12: 157-162, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11210186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11210186</a>] [<a href="https://doi.org/10.1007/s003350010247" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11210186">Lee et al. (2001)</a> mapped NKX6B gene to 10q26, a region where loss of heterozygosity has frequently been observed in various malignant brain tumors. <a href="#4" class="mim-tip-reference" title="Lee, S.-H., Davison, J. A., Vidal, S. M., Belouchi, A. <strong>Cloning, expression and chromosomal location of NKX6B to 10q26, a region frequently deleted in brain tumors.</strong> Mammalian Genome 12: 157-162, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11210186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11210186</a>] [<a href="https://doi.org/10.1007/s003350010247" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11210186">Lee et al. (2001)</a> suggested that NKX6B may be a tumor suppressor gene for brain tumors, particularly for oligodendrogliomas. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11210186" 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="Komuro, I., Schalling, M., Jahn, L., Bodmer, R., Jenkins, N. A., Copeland, G. A., Izumo, S. <strong>Gtx: a novel murine homeobox-containing gene, expressed specifically in glial cells of the brain and germ cells of testis, has a transcriptional repressor activity in vitro for a serum-inducible promoter.</strong> EMBO J. 12: 1387-1401, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8096811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8096811</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1993.tb05783.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8096811">Komuro et al. (1993)</a> mapped the mouse Nkx6b gene to the distal portion of chromosome 7. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8096811" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using in silico analysis, gene-regulatory networks, and coexpression data in humans, <a href="#1" class="mim-tip-reference" title="Chelban, V., Patel, N., Vandrovcova, J., Zanetti, M. N., Lynch, D. S., Ryten, M., Botia, J. A., Bello, O., Tribollet, E., Efthymiou, S., Davagnanam, I., SYNAPSE Study Group, Bashiri, F. A., Wood, N. W., Rothman, J. E., Alkuraya, F. S., Houlden, H. <strong>Mutations in NKX6-2 cause progressive spastic ataxia and hypomyelination.</strong> Am. J. Hum. Genet. 100: 969-977, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28575651/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28575651</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28575651[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2017.05.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28575651">Chelban et al. (2017)</a> concluded that NKX6-2 is involved in the genesis and development of oligodendrocytes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28575651" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In 7 patients from 3 unrelated families with autosomal recessive spastic ataxia-8 (SPAX8; <a href="/entry/617560">617560</a>), <a href="#1" class="mim-tip-reference" title="Chelban, V., Patel, N., Vandrovcova, J., Zanetti, M. N., Lynch, D. S., Ryten, M., Botia, J. A., Bello, O., Tribollet, E., Efthymiou, S., Davagnanam, I., SYNAPSE Study Group, Bashiri, F. A., Wood, N. W., Rothman, J. E., Alkuraya, F. S., Houlden, H. <strong>Mutations in NKX6-2 cause progressive spastic ataxia and hypomyelination.</strong> Am. J. Hum. Genet. 100: 969-977, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28575651/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28575651</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28575651[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2017.05.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28575651">Chelban et al. (2017)</a> identified homozygous mutations in the NKX6-2 gene (K41X, <a href="#0001">605955.0001</a> and L163V, <a href="#0002">605955.0002</a>). The mutations, which were found by exome sequencing, segregated with the disorder in the families. Cells from a patient with the nonsense mutation showed absence of the truncated protein, consistent with a complete loss of function; functional studies and studies of patients cells with the missense mutation were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28575651" 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="#2" class="mim-tip-reference" title="Dorboz, I., Aiello, C., Simons, C., Stone, R. T., Niceta, M., Elmaleh, M., Abuawad, M., Doummar, D., Bruselles, A., Wolf, N. I., Travaglini, L., Boespflug-Tanguy, O., Tartaglia, M., Vanderver, A., Rodriguez, D., Bertini, E. <strong>Biallelic mutations in the homeodomain of NKX6-2 underlie a severe hypomyelinating leukodystrophy.</strong> Brain 140: 2550-2556, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28969374/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28969374</a>] [<a href="https://doi.org/10.1093/brain/awx207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28969374">Dorboz et al. (2017)</a> identified biallelic mutations in the NKX6-2 gene in 5 patients, including 2 sib pairs, from 3 unrelated families with SPAX8. The patients from families 1 and 2 had homozygous mutations (<a href="#0003">605955.0003</a> and <a href="#0004">605955.0004</a>) and the sibs from family 3 had compound heterozygous mutations (<a href="#0005">605955.0005</a> and <a href="#0006">605955.0006</a>). The mutations, which were identified by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. Functional studies in patient cells were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28969374" 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="Vallstedt, A., Muhr, J., Pattyn, A., Pierani, A., Mendelsohn, M., Sander, M., Jessell, T. M., Ericson, J. <strong>Different levels of repressor activity assign redundant and specific roles to Nkx6 genes in motor neuron and interneuron specification.</strong> Neuron 31: 743-755, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11567614/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11567614</a>] [<a href="https://doi.org/10.1016/s0896-6273(01)00412-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11567614">Vallstedt et al. (2001)</a> obtained Nkx6-2 -/- mice at the expected mendelian ratio, and Nkx6-2 -/- mice survived through adulthood. Examination of progenitor cell fate in embryonic Nkx6-2 -/- spinal cord suggested that Nkx6-2 in p1 progenitor cells promoted generation of V1 interneurons and helped to suppress V0 interneurons. Use of Nkx6-1/Nkx6-2 compound mutant embryos revealed that Nkx6-1 and Nkx6-2 had an equivalent inhibitory influence of generation of V0 interneurons. Nkx6-1 and Nkx6-2 also had additive effects, with higher or lower total Nkx6 content directing progenitors to different interneuron or motor neuron cell fates. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11567614" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Southwood, C., He, C., Garbern, J., Kamholz, J., Arroyo, E., Gow, A. <strong>CNS myelin paranodes require Nkx6-2 homeoprotein transcriptional activity for normal structure.</strong> J. Neurosci. 24: 11215-11225, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15601927/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15601927</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15601927[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/10.1523/JNEUROSCI.3479-04.2004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15601927">Southwood et al. (2004)</a> found that Nkx6-2-null mice had deficits in motor coordination and nerve conduction in the central nervous system. These abnormalities were associated with myelination defects at paranodal junctions, particularly in the optic nerve, and aberrant expression of downstream genes involved in cytoskeletal and cell adhesion functions. The findings suggested a role for Nkx6-2 in the regulation of axon-glial interactions at myelin paranodes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15601927" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>6 Selected Examples</a>):</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=605955[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<strong>.0001 SPASTIC ATAXIA 8, AUTOSOMAL RECESSIVE, WITH HYPOMYELINATING LEUKODYSTROPHY</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">rs1131692047 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1131692047;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=rs1131692047" 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=rs1131692047" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 5 patients from 2 unrelated consanguineous families with spastic ataxia-8 with hypomyelinating leukodystrophy (SPAX8; <a href="/entry/617560">617560</a>), <a href="#1" class="mim-tip-reference" title="Chelban, V., Patel, N., Vandrovcova, J., Zanetti, M. N., Lynch, D. S., Ryten, M., Botia, J. A., Bello, O., Tribollet, E., Efthymiou, S., Davagnanam, I., SYNAPSE Study Group, Bashiri, F. A., Wood, N. W., Rothman, J. E., Alkuraya, F. S., Houlden, H. <strong>Mutations in NKX6-2 cause progressive spastic ataxia and hypomyelination.</strong> Am. J. Hum. Genet. 100: 969-977, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28575651/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28575651</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28575651[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2017.05.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28575651">Chelban et al. (2017)</a> identified a homozygous c.121A-T transversion (c.121A-T, NM_177400.2) in exon 1 of the NKX6-2 gene, resulting in a lys41-to-ter (K41X) substitution. The mutation, which was found by whole-exome sequencing, segregated with the disorder in both families. It was not found in public databases or in an in-house database of 1,284 ethnically matched exomes. One family was of North Indian descent and the other was of Kenyan and Tanzanian descent; haplotype analysis indicated a founder effect. Analysis of patient cells showed absence of the mutant protein, consistent with a complete loss of function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28575651" 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>.0002 SPASTIC ATAXIA 8, AUTOSOMAL RECESSIVE, WITH HYPOMYELINATING LEUKODYSTROPHY</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">rs1131692048 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1131692048;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=rs1131692048" 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=rs1131692048" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 2 sibs, born of consanguineous Saudi Arabian parents with autosomal recessive spastic ataxia-8 with hypomyelinating leukodystrophy (SPAX8; <a href="/entry/617560">617560</a>), <a href="#1" class="mim-tip-reference" title="Chelban, V., Patel, N., Vandrovcova, J., Zanetti, M. N., Lynch, D. S., Ryten, M., Botia, J. A., Bello, O., Tribollet, E., Efthymiou, S., Davagnanam, I., SYNAPSE Study Group, Bashiri, F. A., Wood, N. W., Rothman, J. E., Alkuraya, F. S., Houlden, H. <strong>Mutations in NKX6-2 cause progressive spastic ataxia and hypomyelination.</strong> Am. J. Hum. Genet. 100: 969-977, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28575651/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28575651</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28575651[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2017.05.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28575651">Chelban et al. (2017)</a> identified a homozygous c.487C-G transversion (c.487C-G, NM_177400.2) in the NKX6-2 gene, resulting in a leu163-to-val (L163V) substitution at a highly conserved residue in the consensus homeobox domain. The mutation, which was found by a combination of homozygosity mapping and exome sequencing, segregated with the disorder in the family. It was not found in the ExAC database and was present only once in heterozygous state in 2,363 control Saudi exomes. Functional studies of the variant and studies of patient cells were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28575651" 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 SPASTIC ATAXIA 8, AUTOSOMAL RECESSIVE, WITH HYPOMYELINATING LEUKODYSTROPHY</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">rs1565019932 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1565019932;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=rs1565019932" 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=rs1565019932" 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=RCV000770993" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000770993" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000770993</a>
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<p>In a male patient, born to consanguineous parents (family 1), with spastic ataxia-8 with hypomyelinating leukodystrophy (SPAX8; <a href="/entry/617560">617560</a>), <a href="#2" class="mim-tip-reference" title="Dorboz, I., Aiello, C., Simons, C., Stone, R. T., Niceta, M., Elmaleh, M., Abuawad, M., Doummar, D., Bruselles, A., Wolf, N. I., Travaglini, L., Boespflug-Tanguy, O., Tartaglia, M., Vanderver, A., Rodriguez, D., Bertini, E. <strong>Biallelic mutations in the homeodomain of NKX6-2 underlie a severe hypomyelinating leukodystrophy.</strong> Brain 140: 2550-2556, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28969374/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28969374</a>] [<a href="https://doi.org/10.1093/brain/awx207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28969374">Dorboz et al. (2017)</a> identified homozygosity for a c.606delinsTA (c.606delinsTA, NM_177400.2) mutation in the NKX6-2 gene, predicted to result in a frameshift and premature termination (Lys202AsnfsTer) in the homeobox domain. The mutation, which was identified by trio whole-exome sequencing and confirmed by Sanger sequencing, was present in the carrier state in the parents. The mutation was not present in the dbSNP (build 147) and ExAC (v.0.3) databases or in an in-house database of over 700 population-matched exomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28969374" 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 SPASTIC ATAXIA 8, AUTOSOMAL RECESSIVE, WITH HYPOMYELINATING LEUKODYSTROPHY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs776560015 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs776560015;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/rs776560015?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=rs776560015" 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=rs776560015" 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=RCV000770990" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000770990" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000770990</a>
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<p>In a brother and sister, born to consanguineous Moroccan parents (family 2), with spastic ataxia-8 with hypomyelinating leukodystrophy (SPAX8; <a href="/entry/617560">617560</a>), <a href="#2" class="mim-tip-reference" title="Dorboz, I., Aiello, C., Simons, C., Stone, R. T., Niceta, M., Elmaleh, M., Abuawad, M., Doummar, D., Bruselles, A., Wolf, N. I., Travaglini, L., Boespflug-Tanguy, O., Tartaglia, M., Vanderver, A., Rodriguez, D., Bertini, E. <strong>Biallelic mutations in the homeodomain of NKX6-2 underlie a severe hypomyelinating leukodystrophy.</strong> Brain 140: 2550-2556, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28969374/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28969374</a>] [<a href="https://doi.org/10.1093/brain/awx207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28969374">Dorboz et al. (2017)</a> identified homozygosity for a c.565G-T transversion (c.565G-T, NM_177400.2) in the NKX6-2 gene, resulting in a glu189-to-ter (E189X) substitution in the homeobox domain. The mutation, which was identified by SNP-based homozygosity mapping and whole-exome sequencing, was present in the carrier state in the parents and an unaffected sib. The mutation was not present in public databases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28969374" 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 SPASTIC ATAXIA 8, AUTOSOMAL RECESSIVE, WITH HYPOMYELINATING LEUKODYSTROPHY</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">rs1565019976 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1565019976;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=rs1565019976" 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=rs1565019976" 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=RCV000770991 OR RCV003558575" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000770991, RCV003558575" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000770991...</a>
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<p>In 2 brothers, born to nonconsanguineous parents (family 3), with spastic ataxia-8 with hypomyelinating leukodystrophy (SPAX8; <a href="/entry/617560">617560</a>), <a href="#2" class="mim-tip-reference" title="Dorboz, I., Aiello, C., Simons, C., Stone, R. T., Niceta, M., Elmaleh, M., Abuawad, M., Doummar, D., Bruselles, A., Wolf, N. I., Travaglini, L., Boespflug-Tanguy, O., Tartaglia, M., Vanderver, A., Rodriguez, D., Bertini, E. <strong>Biallelic mutations in the homeodomain of NKX6-2 underlie a severe hypomyelinating leukodystrophy.</strong> Brain 140: 2550-2556, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28969374/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28969374</a>] [<a href="https://doi.org/10.1093/brain/awx207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28969374">Dorboz et al. (2017)</a> identified compound heterozygous mutations in exon 3 of the NKX6-2 gene, a maternally inherited c.589C-T transition (c.589C-T, NM_177400.2), resulting in a gln197-to-ter (Q197X) substitution, and a paternally inherited c.599G-A transition, resulting in an arg200-to-gln (R200Q; <a href="#0006">605955.0006</a>) substitution. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, were present in the carrier state in the parents. Both mutations were in the homeobox domain, and the R200Q mutation was predicted to affect DNA binding. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28969374" 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>.0006 SPASTIC ATAXIA 8, AUTOSOMAL RECESSIVE, WITH HYPOMYELINATING LEUKODYSTROPHY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs1008088032 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1008088032;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/rs1008088032?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=rs1008088032" 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=rs1008088032" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>For discussion of the c.599G-A transition (c.599G-A, NM_177400.2) in the NKX6-2 gene, resulting in an arg200-to-gln (R200Q) substitution, that was identified in compound heterozygous state in 2 sibs with spastic ataxia-8 with hypomyelinating leukodystrophy (SPAX8; <a href="/entry/617560">617560</a>) by <a href="#2" class="mim-tip-reference" title="Dorboz, I., Aiello, C., Simons, C., Stone, R. T., Niceta, M., Elmaleh, M., Abuawad, M., Doummar, D., Bruselles, A., Wolf, N. I., Travaglini, L., Boespflug-Tanguy, O., Tartaglia, M., Vanderver, A., Rodriguez, D., Bertini, E. <strong>Biallelic mutations in the homeodomain of NKX6-2 underlie a severe hypomyelinating leukodystrophy.</strong> Brain 140: 2550-2556, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28969374/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28969374</a>] [<a href="https://doi.org/10.1093/brain/awx207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28969374">Dorboz et al. (2017)</a>, see <a href="#0005">605955.0005</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28969374" 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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<a id="1" class="mim-anchor"></a>
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|
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Chelban, V., Patel, N., Vandrovcova, J., Zanetti, M. N., Lynch, D. S., Ryten, M., Botia, J. A., Bello, O., Tribollet, E., Efthymiou, S., Davagnanam, I., SYNAPSE Study Group, Bashiri, F. A., Wood, N. W., Rothman, J. E., Alkuraya, F. S., Houlden, H.
|
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<strong>Mutations in NKX6-2 cause progressive spastic ataxia and hypomyelination.</strong>
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Am. J. Hum. Genet. 100: 969-977, 2017.
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28575651/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28575651</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28575651[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=28575651" 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.ajhg.2017.05.009" target="_blank">Full Text</a>]
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Dorboz, I., Aiello, C., Simons, C., Stone, R. T., Niceta, M., Elmaleh, M., Abuawad, M., Doummar, D., Bruselles, A., Wolf, N. I., Travaglini, L., Boespflug-Tanguy, O., Tartaglia, M., Vanderver, A., Rodriguez, D., Bertini, E.
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<strong>Biallelic mutations in the homeodomain of NKX6-2 underlie a severe hypomyelinating leukodystrophy.</strong>
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Brain 140: 2550-2556, 2017.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28969374/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28969374</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28969374" 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/brain/awx207" target="_blank">Full Text</a>]
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Komuro, I., Schalling, M., Jahn, L., Bodmer, R., Jenkins, N. A., Copeland, G. A., Izumo, S.
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<strong>Gtx: a novel murine homeobox-containing gene, expressed specifically in glial cells of the brain and germ cells of testis, has a transcriptional repressor activity in vitro for a serum-inducible promoter.</strong>
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EMBO J. 12: 1387-1401, 1993.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8096811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8096811</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8096811" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Lee, S.-H., Davison, J. A., Vidal, S. M., Belouchi, A.
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<strong>Cloning, expression and chromosomal location of NKX6B to 10q26, a region frequently deleted in brain tumors.</strong>
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Mammalian Genome 12: 157-162, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11210186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11210186</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11210186" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Southwood, C., He, C., Garbern, J., Kamholz, J., Arroyo, E., Gow, A.
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<strong>CNS myelin paranodes require Nkx6-2 homeoprotein transcriptional activity for normal structure.</strong>
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J. Neurosci. 24: 11215-11225, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15601927/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15601927</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15601927[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=15601927" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Vallstedt, A., Muhr, J., Pattyn, A., Pierani, A., Mendelsohn, M., Sander, M., Jessell, T. M., Ericson, J.
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<strong>Different levels of repressor activity assign redundant and specific roles to Nkx6 genes in motor neuron and interneuron specification.</strong>
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Neuron 31: 743-755, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11567614/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11567614</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11567614" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Hilary J. Vernon - updated : 05/22/2024
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Cassandra L. Kniffin - updated : 07/05/2017<br>Patricia A. Hartz - updated : 06/02/2016
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<span class="text-nowrap mim-text-font">
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Creation Date:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 5/22/2001
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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carol : 05/22/2024
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carol : 01/02/2020<br>carol : 12/30/2019<br>carol : 10/18/2017<br>carol : 07/07/2017<br>ckniffin : 07/05/2017<br>mgross : 06/02/2016<br>alopez : 3/26/2012<br>wwang : 8/11/2005<br>terry : 3/18/2004<br>cwells : 5/31/2001<br>mgross : 5/22/2001
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<span class="mim-font">
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<strong>*</strong> 605955
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<h3>
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<span class="mim-font">
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NK6 HOMEOBOX 2; NKX6-2
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<h4>
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<span class="mim-font">
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NK6, DROSOPHILA, HOMOLOG OF, 2<br />
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HOMEOBOX 6B, NK<br />
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NK HOMEOBOX, FAMILY 6, MEMBER B; NKX6B<br />
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NKX6.2, MOUSE, HOMOLOG OF
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: NKX6-2</em></strong>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 1217379007;
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<strong>
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<em>
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Cytogenetic location: 10q26.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 10:132,783,181-132,786,147 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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<table class="table table-bordered table-condensed small mim-table-padding">
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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<td rowspan="1">
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<span class="mim-font">
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10q26.3
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<span class="mim-font">
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Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy
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</td>
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<span class="mim-font">
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617560
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<span class="mim-font">
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Autosomal recessive
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<span class="mim-font">
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3
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<span class="mim-font">
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<strong>TEXT</strong>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>The NKX6-2 gene encodes a member of the NKX protein family of transcription factors, which have established roles during the development of an organism (summary by Chelban et al., 2017). </p><p>Homeobox genes act as master genes that control pattern formation and positional information during embryonic development. In the adult, they are thought to maintain the differentiated states of cell populations and to direct the renewal of specific cell types. While homeobox genes are widely expressed in the developing vertebrate nervous system, only a few, including NKX6B, continue to be expressed in the adult brain (summary by Lee et al., 2001). </p>
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</span>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</h4>
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<p>Nkx6.2 was isolated in mouse by Komuro et al. (1993). Expression of Nkx6.2 appeared to be tissue specific and developmentally regulated. In day-18 mouse embryos, it was expressed in part of the forebrain as well as in mid- and hindbrain, whereas in the adult CNS, expression was most abundant in areas rich in oligodendrocyte cell bodies and astrocytes. Together with DNA binding assays, these expression studies suggested that the Nkx6.2 gene product may be important for differentiated oligodendrocyte function and in the regulation of myelin gene expression. </p><p>Lee et al. (2001) cloned and characterized NKX6B, the human homolog of mouse Nkx6.2. The predicted 277-amino acid NKX6B protein shares 97% identity with mouse Nkx6.2 and 52% homology with NKX6A (NKX6-1; 602563). Northern blot analysis showed that NKX6B expression is tightly controlled in a tissue-specific fashion, with highest expression in brain. </p><p>Using immunohistochemistry and in situ hybridization, Vallstedt et al. (2001) detected expression of Nkx6-2 first in the caudal neural tube in a broad ventral domain at approximately embryonic day 8.5. Nkx6-2 was expressed predominantly within the dorsal progenitor p1 domain and more weakly in the p0 domain. </p><p>In embryonic mice, Southwood et al. (2004) found expression of Nkx6-2 in cranial nerves, interneuron precursors, and motoneurons that extend axons into the periphery. Nkx6-2 continued to be expressed in the nucleus of oligodendrocytes in adult mouse brain. </p>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By DNA sequence analysis of an 11-kb genomic fragment, Lee et al. (2001) demonstrated that the NKX6B gene spans 1.2 kb and contains 3 exons. </p>
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</span>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Using STS content mapping and radiation hybrid analysis, Lee et al. (2001) mapped NKX6B gene to 10q26, a region where loss of heterozygosity has frequently been observed in various malignant brain tumors. Lee et al. (2001) suggested that NKX6B may be a tumor suppressor gene for brain tumors, particularly for oligodendrogliomas. </p><p>Komuro et al. (1993) mapped the mouse Nkx6b gene to the distal portion of chromosome 7. </p>
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</span>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Using in silico analysis, gene-regulatory networks, and coexpression data in humans, Chelban et al. (2017) concluded that NKX6-2 is involved in the genesis and development of oligodendrocytes. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In 7 patients from 3 unrelated families with autosomal recessive spastic ataxia-8 (SPAX8; 617560), Chelban et al. (2017) identified homozygous mutations in the NKX6-2 gene (K41X, 605955.0001 and L163V, 605955.0002). The mutations, which were found by exome sequencing, segregated with the disorder in the families. Cells from a patient with the nonsense mutation showed absence of the truncated protein, consistent with a complete loss of function; functional studies and studies of patients cells with the missense mutation were not performed. </p><p>Dorboz et al. (2017) identified biallelic mutations in the NKX6-2 gene in 5 patients, including 2 sib pairs, from 3 unrelated families with SPAX8. The patients from families 1 and 2 had homozygous mutations (605955.0003 and 605955.0004) and the sibs from family 3 had compound heterozygous mutations (605955.0005 and 605955.0006). The mutations, which were identified by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. Functional studies in patient cells were not performed. </p>
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</span>
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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>Animal Model</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>Vallstedt et al. (2001) obtained Nkx6-2 -/- mice at the expected mendelian ratio, and Nkx6-2 -/- mice survived through adulthood. Examination of progenitor cell fate in embryonic Nkx6-2 -/- spinal cord suggested that Nkx6-2 in p1 progenitor cells promoted generation of V1 interneurons and helped to suppress V0 interneurons. Use of Nkx6-1/Nkx6-2 compound mutant embryos revealed that Nkx6-1 and Nkx6-2 had an equivalent inhibitory influence of generation of V0 interneurons. Nkx6-1 and Nkx6-2 also had additive effects, with higher or lower total Nkx6 content directing progenitors to different interneuron or motor neuron cell fates. </p><p>Southwood et al. (2004) found that Nkx6-2-null mice had deficits in motor coordination and nerve conduction in the central nervous system. These abnormalities were associated with myelination defects at paranodal junctions, particularly in the optic nerve, and aberrant expression of downstream genes involved in cytoskeletal and cell adhesion functions. The findings suggested a role for Nkx6-2 in the regulation of axon-glial interactions at myelin paranodes. </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>ALLELIC VARIANTS</strong>
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</span>
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<strong>6 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 SPASTIC ATAXIA 8, AUTOSOMAL RECESSIVE, WITH HYPOMYELINATING LEUKODYSTROPHY</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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NKX6-2, LYS41TER
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<br />
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SNP: rs1131692047,
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ClinVar: RCV000494722
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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 5 patients from 2 unrelated consanguineous families with spastic ataxia-8 with hypomyelinating leukodystrophy (SPAX8; 617560), Chelban et al. (2017) identified a homozygous c.121A-T transversion (c.121A-T, NM_177400.2) in exon 1 of the NKX6-2 gene, resulting in a lys41-to-ter (K41X) substitution. The mutation, which was found by whole-exome sequencing, segregated with the disorder in both families. It was not found in public databases or in an in-house database of 1,284 ethnically matched exomes. One family was of North Indian descent and the other was of Kenyan and Tanzanian descent; haplotype analysis indicated a founder effect. Analysis of patient cells showed absence of the mutant protein, consistent with a complete loss of function. </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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<h4>
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<span class="mim-font">
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<strong>.0002 SPASTIC ATAXIA 8, AUTOSOMAL RECESSIVE, WITH HYPOMYELINATING LEUKODYSTROPHY</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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NKX6-2, LEU163VAL
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<br />
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SNP: rs1131692048,
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ClinVar: RCV000494724
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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 2 sibs, born of consanguineous Saudi Arabian parents with autosomal recessive spastic ataxia-8 with hypomyelinating leukodystrophy (SPAX8; 617560), Chelban et al. (2017) identified a homozygous c.487C-G transversion (c.487C-G, NM_177400.2) in the NKX6-2 gene, resulting in a leu163-to-val (L163V) substitution at a highly conserved residue in the consensus homeobox domain. The mutation, which was found by a combination of homozygosity mapping and exome sequencing, segregated with the disorder in the family. It was not found in the ExAC database and was present only once in heterozygous state in 2,363 control Saudi exomes. Functional studies of the variant and studies of patient cells were not performed. </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 SPASTIC ATAXIA 8, AUTOSOMAL RECESSIVE, WITH HYPOMYELINATING LEUKODYSTROPHY</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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NKX6-2, 1-BP DEL/2-BP INS, NT606
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<br />
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SNP: rs1565019932,
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ClinVar: RCV000770993
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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 male patient, born to consanguineous parents (family 1), with spastic ataxia-8 with hypomyelinating leukodystrophy (SPAX8; 617560), Dorboz et al. (2017) identified homozygosity for a c.606delinsTA (c.606delinsTA, NM_177400.2) mutation in the NKX6-2 gene, predicted to result in a frameshift and premature termination (Lys202AsnfsTer) in the homeobox domain. The mutation, which was identified by trio whole-exome sequencing and confirmed by Sanger sequencing, was present in the carrier state in the parents. The mutation was not present in the dbSNP (build 147) and ExAC (v.0.3) databases or in an in-house database of over 700 population-matched exomes. </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 SPASTIC ATAXIA 8, AUTOSOMAL RECESSIVE, WITH HYPOMYELINATING LEUKODYSTROPHY</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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NKX6-2, GLU189TER
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<br />
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SNP: rs776560015,
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gnomAD: rs776560015,
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ClinVar: RCV000770990
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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 brother and sister, born to consanguineous Moroccan parents (family 2), with spastic ataxia-8 with hypomyelinating leukodystrophy (SPAX8; 617560), Dorboz et al. (2017) identified homozygosity for a c.565G-T transversion (c.565G-T, NM_177400.2) in the NKX6-2 gene, resulting in a glu189-to-ter (E189X) substitution in the homeobox domain. The mutation, which was identified by SNP-based homozygosity mapping and whole-exome sequencing, was present in the carrier state in the parents and an unaffected sib. The mutation was not present in public databases. </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>.0005 SPASTIC ATAXIA 8, AUTOSOMAL RECESSIVE, WITH HYPOMYELINATING LEUKODYSTROPHY</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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NKX6-2, GLN197TER
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<br />
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SNP: rs1565019976,
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ClinVar: RCV000770991, RCV003558575
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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 2 brothers, born to nonconsanguineous parents (family 3), with spastic ataxia-8 with hypomyelinating leukodystrophy (SPAX8; 617560), Dorboz et al. (2017) identified compound heterozygous mutations in exon 3 of the NKX6-2 gene, a maternally inherited c.589C-T transition (c.589C-T, NM_177400.2), resulting in a gln197-to-ter (Q197X) substitution, and a paternally inherited c.599G-A transition, resulting in an arg200-to-gln (R200Q; 605955.0006) substitution. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, were present in the carrier state in the parents. Both mutations were in the homeobox domain, and the R200Q mutation was predicted to affect DNA binding. </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>.0006 SPASTIC ATAXIA 8, AUTOSOMAL RECESSIVE, WITH HYPOMYELINATING LEUKODYSTROPHY</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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NKX6-2, ARG200GLN
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<br />
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SNP: rs1008088032,
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gnomAD: rs1008088032,
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ClinVar: RCV000770992
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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>For discussion of the c.599G-A transition (c.599G-A, NM_177400.2) in the NKX6-2 gene, resulting in an arg200-to-gln (R200Q) substitution, that was identified in compound heterozygous state in 2 sibs with spastic ataxia-8 with hypomyelinating leukodystrophy (SPAX8; 617560) by Dorboz et al. (2017), see 605955.0005. </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>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Chelban, V., Patel, N., Vandrovcova, J., Zanetti, M. N., Lynch, D. S., Ryten, M., Botia, J. A., Bello, O., Tribollet, E., Efthymiou, S., Davagnanam, I., SYNAPSE Study Group, Bashiri, F. A., Wood, N. W., Rothman, J. E., Alkuraya, F. S., Houlden, H.
|
|
<strong>Mutations in NKX6-2 cause progressive spastic ataxia and hypomyelination.</strong>
|
|
Am. J. Hum. Genet. 100: 969-977, 2017.
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[PubMed: 28575651]
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[Full Text: https://doi.org/10.1016/j.ajhg.2017.05.009]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Dorboz, I., Aiello, C., Simons, C., Stone, R. T., Niceta, M., Elmaleh, M., Abuawad, M., Doummar, D., Bruselles, A., Wolf, N. I., Travaglini, L., Boespflug-Tanguy, O., Tartaglia, M., Vanderver, A., Rodriguez, D., Bertini, E.
|
|
<strong>Biallelic mutations in the homeodomain of NKX6-2 underlie a severe hypomyelinating leukodystrophy.</strong>
|
|
Brain 140: 2550-2556, 2017.
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[PubMed: 28969374]
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[Full Text: https://doi.org/10.1093/brain/awx207]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Komuro, I., Schalling, M., Jahn, L., Bodmer, R., Jenkins, N. A., Copeland, G. A., Izumo, S.
|
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<strong>Gtx: a novel murine homeobox-containing gene, expressed specifically in glial cells of the brain and germ cells of testis, has a transcriptional repressor activity in vitro for a serum-inducible promoter.</strong>
|
|
EMBO J. 12: 1387-1401, 1993.
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[PubMed: 8096811]
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[Full Text: https://doi.org/10.1002/j.1460-2075.1993.tb05783.x]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Lee, S.-H., Davison, J. A., Vidal, S. M., Belouchi, A.
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<strong>Cloning, expression and chromosomal location of NKX6B to 10q26, a region frequently deleted in brain tumors.</strong>
|
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Mammalian Genome 12: 157-162, 2001.
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[PubMed: 11210186]
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[Full Text: https://doi.org/10.1007/s003350010247]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Southwood, C., He, C., Garbern, J., Kamholz, J., Arroyo, E., Gow, A.
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<strong>CNS myelin paranodes require Nkx6-2 homeoprotein transcriptional activity for normal structure.</strong>
|
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J. Neurosci. 24: 11215-11225, 2004.
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[PubMed: 15601927]
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[Full Text: https://doi.org/10.1523/JNEUROSCI.3479-04.2004]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Vallstedt, A., Muhr, J., Pattyn, A., Pierani, A., Mendelsohn, M., Sander, M., Jessell, T. M., Ericson, J.
|
|
<strong>Different levels of repressor activity assign redundant and specific roles to Nkx6 genes in motor neuron and interneuron specification.</strong>
|
|
Neuron 31: 743-755, 2001.
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|
|
[PubMed: 11567614]
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[Full Text: https://doi.org/10.1016/s0896-6273(01)00412-3]
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</p>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div class="row">
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Contributors:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
|
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Hilary J. Vernon - updated : 05/22/2024<br>Cassandra L. Kniffin - updated : 07/05/2017<br>Patricia A. Hartz - updated : 06/02/2016
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</span>
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</div>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 5/22/2001
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carol : 05/22/2024<br>carol : 01/02/2020<br>carol : 12/30/2019<br>carol : 10/18/2017<br>carol : 07/07/2017<br>ckniffin : 07/05/2017<br>mgross : 06/02/2016<br>alopez : 3/26/2012<br>wwang : 8/11/2005<br>terry : 3/18/2004<br>cwells : 5/31/2001<br>mgross : 5/22/2001
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