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Entry
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- *611595 - THIOREDOXIN-LIKE 4A; TXNL4A
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- OMIM
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<p>
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<span class="h4">*611595</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#biochemicalFeatures">Biochemical Features</a>
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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="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/611595">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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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<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 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 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=ENSG00000141759;t=ENST00000269601" 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=10907" 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=611595" 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 class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000141759;t=ENST00000269601" 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_001303471,NM_001305557,NM_001305563,NM_001305564,NM_006701,NR_131175,NR_131176,NR_131177" 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_006701" 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=611595" 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=18252&isoform_id=18252_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/TXNL4A" 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/2565275,2565277,5729802,6572636,12654441,17939455,46577662,119587043,119587044,119587045,189067433,744066809,770478874,770478876,770478878" 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/P83876" 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=10907" 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=ENSG00000141759;t=ENST00000269601" 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=TXNL4A" 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=TXNL4A" 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+10907" 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/TXNL4A" 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:10907" 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/10907" 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=chr18&hgg_gene=ENST00000269601.10&hgg_start=79970813&hgg_end=80033936&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 class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:30551" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/txnl4a" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=611595[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=611595[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000141759" 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=TXNL4A" 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=TXNL4A" 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=TXNL4A" 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=TXNL4A&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/PA134937290" 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:30551" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0031601.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1351613" 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/TXNL4A#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:1351613" 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/10907/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=10907" 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=WBGene00235102;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-041010-25" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:10907" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=TXNL4A&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> 720640005<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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611595
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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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THIOREDOXIN-LIKE 4A; TXNL4A
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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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DIM1, S. POMBE, HOMOLOG OF; DIM1<br />
|
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U5 snRNP-SPECIFIC PROTEIN, 15-KD<br />
|
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U5-15KD
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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=TXNL4A" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">TXNL4A</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/18/273?start=-3&limit=10&highlight=273">18q23</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr18:79970813-80033936&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'})">18:79,970,813-80,033,936</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">
|
|
<a href="/geneMap/18/273?start=-3&limit=10&highlight=273">
|
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18q23
|
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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">
|
|
Burn-McKeown syndrome
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<a href="/entry/608572"> 608572 </a>
|
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|
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</span>
|
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</td>
|
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<td>
|
|
<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">
|
|
<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;">
|
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<li><a href="/graph/linear/611595" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/611595" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
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<br />
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</div>
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<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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<p>By SDS-PAGE of human 20S U5 snRNP, followed by EST database analysis, and PCR of a HeLa cell cDNA library, <a href="#5" class="mim-tip-reference" title="Reuter, K., Nottrott, S., Fabrizio, P., Luhrmann, R., Ficner, R. <strong>Identification, characterization and crystal structure analysis of the human spliceosomal U5 snRNP-specific 15 kD protein.</strong> J. Molec. Biol. 294: 515-525, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10610776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10610776</a>] [<a href="https://doi.org/10.1006/jmbi.1999.3258" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10610776">Reuter et al. (1999)</a> cloned TXNL4A, which they called U5-15KD. The deduced protein contained 142 amino acids and contains a thioredoxin-like domain. TXNL4A shares 66% sequence identity with the S. cerevisiae homolog Dib1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10610776" 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="#8" class="mim-tip-reference" title="Wood, K. A., Ellingford, J. M., Thomas, H. B., Genomics UK Research Consortium, Douzgou, S., Beaman, G. M., Hobson, E., Prescott, K., O'Keefe, R. T., Newman, W. G. <strong>Expanding the genotypic spectrum of TXNL4A variants in Burn-McKeown syndrome.</strong> Clin. Genet. 101: 255-259, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34713892/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34713892</a>] [<a href="https://doi.org/10.1111/cge.14082" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34713892">Wood et al. (2022)</a> determined that the TXNL4A promoter region consists of two 22-bp repeated motifs (RR1 and RR2) separated by a 12-bp spacer. They identified potential binding sites for 4 transcription factors, XBP1 (<a href="/entry/194355">194355</a>), c-JUN (see <a href="/entry/165160">165160</a>), AHR/ARNT (see <a href="/entry/600253">600253</a>), and ATF3 (<a href="/entry/603148">603148</a>). Dual luciferase assays demonstrated that RR1 and RR2 contain the critical nucleotides necessary for TXNL4A promoter activity and that RR1 and RR2 act independently and cumulatively to promote TXNL4A expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34713892" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Wood, K. A., Ellingford, J. M., Thomas, H. B., Genomics UK Research Consortium, Douzgou, S., Beaman, G. M., Hobson, E., Prescott, K., O'Keefe, R. T., Newman, W. G. <strong>Expanding the genotypic spectrum of TXNL4A variants in Burn-McKeown syndrome.</strong> Clin. Genet. 101: 255-259, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34713892/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34713892</a>] [<a href="https://doi.org/10.1111/cge.14082" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34713892">Wood et al. (2022)</a> determined that the TXNL4A gene contains 3 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34713892" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#2" class="mim-tip-reference" title="Gross, M. B. <strong>Personal Communication.</strong> Baltimore, Md. 4/6/2018."None>Gross (2018)</a> mapped the TXNL4A gene to chromosome 18q23 based on an alignment of the TXNL4A sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=AF146373" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">AF146373</a>) with the genomic sequence (GRCh38).</p>
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<a href="#5" class="mim-tip-reference" title="Reuter, K., Nottrott, S., Fabrizio, P., Luhrmann, R., Ficner, R. <strong>Identification, characterization and crystal structure analysis of the human spliceosomal U5 snRNP-specific 15 kD protein.</strong> J. Molec. Biol. 294: 515-525, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10610776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10610776</a>] [<a href="https://doi.org/10.1006/jmbi.1999.3258" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10610776">Reuter et al. (1999)</a> analyzed the crystal structure of U5-15KD at 1.4-angstrom resolution and determined that it has a thioredoxin (TXN; <a href="/entry/187700">187700</a>)-like fold with a 4-stranded beta-sheet composed of pairs of parallel and antiparallel strands flanked by 3 alpha-helices. Compared to human thioredoxin, U5-15KD contains an additional 37 amino acid residues. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10610776" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Zhang, Y.-Z., Gould, K. L., Dunbrack, R. L., Jr., Cheng, H., Roder, H., Golemis, E. A. <strong>The evolutionarily conserved Dim1 protein defines a novel branch of the thioredoxin fold superfamily.</strong> Physiol. Genomics 1: 109-118, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11015569/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11015569</a>] [<a href="https://doi.org/10.1152/physiolgenomics.1999.1.3.109" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11015569">Zhang et al. (1999)</a> used protein-threading search algorithms and multidimensional NMR methods and also determined that the human DIM1 protein adopts a thioredoxin fold. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11015569" 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 genetic depletion of Dib1 in S. cerevisiae, <a href="#5" class="mim-tip-reference" title="Reuter, K., Nottrott, S., Fabrizio, P., Luhrmann, R., Ficner, R. <strong>Identification, characterization and crystal structure analysis of the human spliceosomal U5 snRNP-specific 15 kD protein.</strong> J. Molec. Biol. 294: 515-525, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10610776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10610776</a>] [<a href="https://doi.org/10.1006/jmbi.1999.3258" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10610776">Reuter et al. (1999)</a> showed that Dib1 is strictly required for pre-mRNA splicing in vivo. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10610776" 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 E. coli overexpressing DIM1, <a href="#9" class="mim-tip-reference" title="Zhang, Y.-Z., Gould, K. L., Dunbrack, R. L., Jr., Cheng, H., Roder, H., Golemis, E. A. <strong>The evolutionarily conserved Dim1 protein defines a novel branch of the thioredoxin fold superfamily.</strong> Physiol. Genomics 1: 109-118, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11015569/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11015569</a>] [<a href="https://doi.org/10.1152/physiolgenomics.1999.1.3.109" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11015569">Zhang et al. (1999)</a> identified a cleaved form of human DIM1 (residues 1-128) truncated immediately after the predicted thioredoxin homology region. They showed that cleaved DIM1 induced lethality in a dominant-negative manner when expressed in S. pombe. By using conditional mutant S. pombe strains, they showed that cleaved DIM1 induced cell cycle arrest at G2 phase. <a href="#9" class="mim-tip-reference" title="Zhang, Y.-Z., Gould, K. L., Dunbrack, R. L., Jr., Cheng, H., Roder, H., Golemis, E. A. <strong>The evolutionarily conserved Dim1 protein defines a novel branch of the thioredoxin fold superfamily.</strong> Physiol. Genomics 1: 109-118, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11015569/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11015569</a>] [<a href="https://doi.org/10.1152/physiolgenomics.1999.1.3.109" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11015569">Zhang et al. (1999)</a> suggested that the short 14-amino acid C-terminal tail of DIM1 is an essential sequence. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11015569" 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="Jin, T., Guo, F., Wang, Y., Zhang, Y.-Z. <strong>Identification of human dim1 as a peptidase with autocleavage activity.</strong> Chem. Biol. Drug. Des. 68: 266-272, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17177886/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17177886</a>] [<a href="https://doi.org/10.1111/j.1747-0285.2006.00447.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17177886">Jin et al. (2006)</a> expressed tagged DIM1 in E. coli and performed enzyme cleavage assays on the purified proteins. They found that DIM1 has peptidase activity and undergoes autocleavage. Protease inhibitors EDTA, chymostatin, and 6-aminohexanoic acid inhibited DIM1 cleavage, and the cleaved dominant-negative form of DIM1 retained the autocleavage activity of the full-length protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17177886" 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 9 of 11 families with Burn-McKeown syndrome (BMKS; <a href="/entry/608572">608572</a>), <a href="#6" class="mim-tip-reference" title="Wieczorek, D., Newman, W. G., Wieland, T., Berulava, T., Kaffe, M., Falkenstein, D., Beetz, C., Graf, E., Schwarzmayr, T., Douzgou, S., Clayton-Smith, J., Daly, S. B., and 30 others. <strong>Compound heterozygosity of low-frequency promoter deletions and rare loss-of-function mutations in TXNL4A causes Burn-McKeown syndrome.</strong> Am. J. Hum. Genet. 95: 698-707, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25434003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25434003</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25434003[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.2014.10.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25434003">Wieczorek et al. (2014)</a> identified biallelic mutations in the TXNL4A gene. Affected members in 8 families were compound heterozygous for a 34-bp deletion in the TXNL4A promoter (designated 'type 1;' <a href="#0001">611595.0001</a>) and a truncating point mutation (<a href="#0002">611595.0002</a>-<a href="#0004">611595.0004</a>) or another deletion (see, e.g., <a href="#0005">611595.0005</a>). In the ninth family, affected individuals were homozygous for an overlapping but different 34-bp TXNL4A promoter deletion (designated 'type 2;' <a href="#0006">611595.0006</a>). Functional analysis revealed that both promoter deletions result in reduced expression of TXNL4A; haplotype analysis was consistent with the promoter deletions occurring due to recurrent events rather than a founder effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25434003" 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 whole-genome sequencing, <a href="#8" class="mim-tip-reference" title="Wood, K. A., Ellingford, J. M., Thomas, H. B., Genomics UK Research Consortium, Douzgou, S., Beaman, G. M., Hobson, E., Prescott, K., O'Keefe, R. T., Newman, W. G. <strong>Expanding the genotypic spectrum of TXNL4A variants in Burn-McKeown syndrome.</strong> Clin. Genet. 101: 255-259, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34713892/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34713892</a>] [<a href="https://doi.org/10.1111/cge.14082" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34713892">Wood et al. (2022)</a> identified compound heterozygous mutations in the TXNL4A gene in 2 patients with BMKS. Both patients carried the type 1 34-bp deletion in the promoter on one allele; on the other allele, one patient had a 2-bp deletion (c.93_94delCC; <a href="#0007">611595.0007</a>) and the other patient had a splice site mutation (c.258-3C-G; <a href="#0008">611595.0008</a>). A minigene splicing assay showed that the c.258-3C-G mutation and a previously described mutation in an adjacent nucleotide in a patient with BKMS (c.258-2A-G) caused skipping of the final exon of TXNL4A. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34713892" 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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<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> rs535089924 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs535089924;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/rs535089924?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=rs535089924" 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=rs535089924" 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=RCV000149583 OR RCV000170535 OR RCV000170536 OR RCV000170538 OR RCV000170539 OR RCV000170540 OR RCV000170541 OR RCV000170542 OR RCV000170543 OR RCV002225453" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000149583, RCV000170535, RCV000170536, RCV000170538, RCV000170539, RCV000170540, RCV000170541, RCV000170542, RCV000170543, RCV002225453" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000149583...</a>
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<p>In affected individuals from 8 families with Burn-McKeown syndrome (BMKS; <a href="/entry/608572">608572</a>), including patients from 2 families originally reported by <a href="#1" class="mim-tip-reference" title="Burn, J., McKeown, C., Wagget, J., Bray, R., Goodship, J. <strong>New dysmorphic syndrome with choanal atresia in siblings.</strong> Clin. Dysmorph. 1: 137-144, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1342861/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1342861</a>]" pmid="1342861">Burn et al. (1992)</a> and the 2 German brothers reported by <a href="#7" class="mim-tip-reference" title="Wieczorek, D., Teber, O. A., Lohmann, D., Gillessen-Kaesbach, G. <strong>Two brothers with Burn-McKeown syndrome.</strong> Clin. Dysmorph. 12: 171-174, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14564154/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14564154</a>] [<a href="https://doi.org/10.1097/01.mcd.0000072163.33788.c4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14564154">Wieczorek et al. (2003)</a>, <a href="#6" class="mim-tip-reference" title="Wieczorek, D., Newman, W. G., Wieland, T., Berulava, T., Kaffe, M., Falkenstein, D., Beetz, C., Graf, E., Schwarzmayr, T., Douzgou, S., Clayton-Smith, J., Daly, S. B., and 30 others. <strong>Compound heterozygosity of low-frequency promoter deletions and rare loss-of-function mutations in TXNL4A causes Burn-McKeown syndrome.</strong> Am. J. Hum. Genet. 95: 698-707, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25434003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25434003</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25434003[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.2014.10.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25434003">Wieczorek et al. (2014)</a> identified compound heterozygosity for a 34-bp deletion in the promoter of the TXNL4A gene (chr18:77,748,581-77,748,614del, GRCh37) and a truncating point mutation (<a href="#0002">611595.0002</a>-<a href="#0004">611595.0004</a>) or deletion involving TXNL4A (see, e.g., <a href="#0005">611595.0005</a>). In each family, the promoter deletion was present in heterozygosity in an unaffected parent. The promoter deletion was not found in the 1000 Genomes Project database; however, analysis of 3,165 population-based samples of German origin and 178 of South Asian origin revealed 45 heterozygous type 1 deletions and 1 homozygous type 1 deletion, for a German allele frequency of 0.76%. Haplotype analysis revealed that the promoter deletions were located on different haplotypes and thus most likely occurred due to recurrent events rather than a founder effect. In the family corresponding to cases 1 and 2 of <a href="#1" class="mim-tip-reference" title="Burn, J., McKeown, C., Wagget, J., Bray, R., Goodship, J. <strong>New dysmorphic syndrome with choanal atresia in siblings.</strong> Clin. Dysmorph. 1: 137-144, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1342861/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1342861</a>]" pmid="1342861">Burn et al. (1992)</a>, the second mutation was a 1.235-Mb terminal deletion (del(18)(q23-qter): 76,841,645-78,077,248, GRCh37); an unrelated affected Vietnamese girl carried an almost identical 1.222-Mb deletion as her second mutation (del(18)(q23-qter): 76,854,774-78,077,248, GRCh37). In the female patient who was case 5 of <a href="#1" class="mim-tip-reference" title="Burn, J., McKeown, C., Wagget, J., Bray, R., Goodship, J. <strong>New dysmorphic syndrome with choanal atresia in siblings.</strong> Clin. Dysmorph. 1: 137-144, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1342861/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1342861</a>]" pmid="1342861">Burn et al. (1992)</a>, the second mutation was a de novo 4.701-Mb terminal deletion on a ring chromosome 18 (46,XX,r(18)(p14q23)arr18q23: 73,376,178-78,077,248, GRCh37). Functional analysis in transfected HEK293 cells demonstrated that the wildtype promoter region enhanced luciferase expression 85-fold compared to control, whereas enhancer activity of the type 1 deletion was reduced by 59% compared to wildtype. Primer extension analysis provided further evidence that the deletion in the promoter region negatively affects transcription, since steady-state transcript levels of the allele carrying wildtype open reading frame (ORF) and the type 1 promoter deletion were reduced compared to transcript levels of the allele with mutant ORF and wildtype promoter. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14564154+25434003+1342861" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Wood, K. A., Ellingford, J. M., Thomas, H. B., Genomics UK Research Consortium, Douzgou, S., Beaman, G. M., Hobson, E., Prescott, K., O'Keefe, R. T., Newman, W. G. <strong>Expanding the genotypic spectrum of TXNL4A variants in Burn-McKeown syndrome.</strong> Clin. Genet. 101: 255-259, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34713892/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34713892</a>] [<a href="https://doi.org/10.1111/cge.14082" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34713892">Wood et al. (2022)</a> identified putative binding sites for 4 transcription factors (XBP1, <a href="/entry/194355">194355</a>; c-JUN, see <a href="/entry/165160">165160</a>; AHR/ARNT, see <a href="/entry/600253">600253</a>; and ATF3, <a href="/entry/603148">603148</a>) within a repeat of a 22-bp motif (RR2) in the 34-bp type 1 deletion region. Deletion of RR2 reduced promoter activity to 45% of wildtype, the same as deletion of the full 34-bp type 1 region. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34713892" 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 BURN-MCKEOWN SYNDROME</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> rs727502793 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs727502793;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/rs727502793?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=rs727502793" 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=rs727502793" 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=RCV000149584 OR RCV003422037" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000149584, RCV003422037" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000149584...</a>
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<p>In 2 German brothers with Burn-McKeown syndrome (BMKS; <a href="/entry/608572">608572</a>), originally reported by <a href="#7" class="mim-tip-reference" title="Wieczorek, D., Teber, O. A., Lohmann, D., Gillessen-Kaesbach, G. <strong>Two brothers with Burn-McKeown syndrome.</strong> Clin. Dysmorph. 12: 171-174, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14564154/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14564154</a>] [<a href="https://doi.org/10.1097/01.mcd.0000072163.33788.c4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14564154">Wieczorek et al. (2003)</a>, <a href="#6" class="mim-tip-reference" title="Wieczorek, D., Newman, W. G., Wieland, T., Berulava, T., Kaffe, M., Falkenstein, D., Beetz, C., Graf, E., Schwarzmayr, T., Douzgou, S., Clayton-Smith, J., Daly, S. B., and 30 others. <strong>Compound heterozygosity of low-frequency promoter deletions and rare loss-of-function mutations in TXNL4A causes Burn-McKeown syndrome.</strong> Am. J. Hum. Genet. 95: 698-707, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25434003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25434003</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25434003[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.2014.10.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25434003">Wieczorek et al. (2014)</a> identified compound heterozygous mutations in the TXNL4A gene: a 34-bp deletion in the promoter (<a href="#0001">611595.0001</a>), and a c.349G-T transversion in exon 3, resulting in a glu117-to-ter (E117X) substitution. The nonsense mutation, which was present in heterozygosity in healthy family members, was not found in the 1000 Genomes Project or dbSNP databases or in 3,000 in-house control exomes from individuals with unrelated diseases. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14564154+25434003" 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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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs727502794 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs727502794;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=rs727502794" 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=rs727502794" 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=RCV000149585" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000149585" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000149585</a>
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<p>In a 34-year-old Swiss man with Burn-McKeown syndrome (BMKS; <a href="/entry/608572">608572</a>), who had bilateral choanal atresia and cleft lip/palate but no reported internal malformations, <a href="#6" class="mim-tip-reference" title="Wieczorek, D., Newman, W. G., Wieland, T., Berulava, T., Kaffe, M., Falkenstein, D., Beetz, C., Graf, E., Schwarzmayr, T., Douzgou, S., Clayton-Smith, J., Daly, S. B., and 30 others. <strong>Compound heterozygosity of low-frequency promoter deletions and rare loss-of-function mutations in TXNL4A causes Burn-McKeown syndrome.</strong> Am. J. Hum. Genet. 95: 698-707, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25434003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25434003</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25434003[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.2014.10.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25434003">Wieczorek et al. (2014)</a> identified compound heterozygous mutations in the TXNL4A gene: a 34-bp deletion in the promoter (<a href="#0001">611595.0001</a>), and a c.37C-T transition in exon 1, resulting in a gln13-to-ter (Q13X) substitution. The nonsense mutation, which was present in heterozygosity in healthy family members, was not found in the 1000 Genomes Project or dbSNP databases or in 3,000 in-house control exomes from individuals with unrelated diseases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25434003" 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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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs727502795 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs727502795;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=rs727502795" 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=rs727502795" 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=RCV000149586" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000149586" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000149586</a>
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<p>In a Pakistani girl with Burn-McKeown syndrome (BMKS; <a href="/entry/608572">608572</a>), who had lower eyelid defects, membranous choanal atresia, cardiac defects, and significant hearing loss with reduced or absent cochlear nerves, <a href="#6" class="mim-tip-reference" title="Wieczorek, D., Newman, W. G., Wieland, T., Berulava, T., Kaffe, M., Falkenstein, D., Beetz, C., Graf, E., Schwarzmayr, T., Douzgou, S., Clayton-Smith, J., Daly, S. B., and 30 others. <strong>Compound heterozygosity of low-frequency promoter deletions and rare loss-of-function mutations in TXNL4A causes Burn-McKeown syndrome.</strong> Am. J. Hum. Genet. 95: 698-707, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25434003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25434003</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25434003[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.2014.10.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25434003">Wieczorek et al. (2014)</a> identified compound heterozygous mutations in the TXNL4A gene: a 34-bp deletion in the promoter (<a href="#0001">611595.0001</a>), and a 1-bp deletion (c.131delT) in exon 1, resulting in a frameshift and a premature termination codon (Val44AlafsTer48). The 1-bp deletion, which was present in heterozygosity in healthy family members, was not found in the 1000 Genomes Project or dbSNP databases or in 3,000 in-house control exomes from individuals with unrelated diseases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25434003" 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 a 3.75-year-old French boy with Burn-McKeown syndrome (BMKS; <a href="/entry/608572">608572</a>), who had lower eyelid defects, bilateral choanal atresia, and unilateral cleft lip but no reported internal malformations, <a href="#6" class="mim-tip-reference" title="Wieczorek, D., Newman, W. G., Wieland, T., Berulava, T., Kaffe, M., Falkenstein, D., Beetz, C., Graf, E., Schwarzmayr, T., Douzgou, S., Clayton-Smith, J., Daly, S. B., and 30 others. <strong>Compound heterozygosity of low-frequency promoter deletions and rare loss-of-function mutations in TXNL4A causes Burn-McKeown syndrome.</strong> Am. J. Hum. Genet. 95: 698-707, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25434003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25434003</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25434003[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.2014.10.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25434003">Wieczorek et al. (2014)</a> identified compound heterozygous mutations in the TXNL4A gene: a 34-bp deletion in the promoter (<a href="#0001">611595.0001</a>) and deletion of exon 3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25434003" 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 affected members of a large Native Alaskan pedigree with Burn-McKeown syndrome (BMKS; <a href="/entry/608572">608572</a>), originally reported by <a href="#3" class="mim-tip-reference" title="Hing, A. V., LeBlond, C., Sze, R. W., Starr, J. R., Monks, S., Parisi, M. A. <strong>A novel oculo-oto-facial dysplasia in a native Alaskan community with autosomal recessive inheritance.</strong> Am. J. Med. Genet. 140A: 804-812, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16523509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16523509</a>] [<a href="https://doi.org/10.1002/ajmg.a.31160" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16523509">Hing et al. (2006)</a>, <a href="#6" class="mim-tip-reference" title="Wieczorek, D., Newman, W. G., Wieland, T., Berulava, T., Kaffe, M., Falkenstein, D., Beetz, C., Graf, E., Schwarzmayr, T., Douzgou, S., Clayton-Smith, J., Daly, S. B., and 30 others. <strong>Compound heterozygosity of low-frequency promoter deletions and rare loss-of-function mutations in TXNL4A causes Burn-McKeown syndrome.</strong> Am. J. Hum. Genet. 95: 698-707, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25434003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25434003</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25434003[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.2014.10.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25434003">Wieczorek et al. (2014)</a> identified homozygosity for a 34-bp deletion in the promoter of the TXNL4A gene, comprising the proximal 33 bp of the 56-bp region, plus the preceding nucleotide (chr18:77,748,604-77,748,637del, GRCh37). This 34-bp 'type 2' promoter deletion overlapped but was different from the 34-bp 'type 1' promoter deletion (<a href="#0001">611595.0001</a>). The mutation segregated with disease in the family; all heterozygous carriers appeared healthy. The type 2 promoter deletion was not found in the 1000 Genomes Project database; however, analysis of 3,165 population-based samples of German origin and 178 of South Asian origin revealed 1 heterozygous type 2 deletion. Functional analysis in transfected HEK293 cells demonstrated that the wildtype promoter region enhanced luciferase expression 85-fold compared to control, whereas enhancer activity of the type 2 deletion was reduced by 72% compared to wildtype. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16523509+25434003" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Wood, K. A., Ellingford, J. M., Thomas, H. B., Genomics UK Research Consortium, Douzgou, S., Beaman, G. M., Hobson, E., Prescott, K., O'Keefe, R. T., Newman, W. G. <strong>Expanding the genotypic spectrum of TXNL4A variants in Burn-McKeown syndrome.</strong> Clin. Genet. 101: 255-259, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34713892/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34713892</a>] [<a href="https://doi.org/10.1111/cge.14082" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34713892">Wood et al. (2022)</a> identified 1 copy of a repeated 22-bp motif (RR1) in the 34-bp type 2 deletion region of the TXNL4A promoter. Deletion of RR1 reduced promoter activity to 54% of wildtype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34713892" 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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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2145089648 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2145089648;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=rs2145089648" 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=rs2145089648" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>By whole-genome sequencing in a woman (family 1) with Burn-McKeown syndrome (BMKS; <a href="/entry/608572">608572</a>), <a href="#8" class="mim-tip-reference" title="Wood, K. A., Ellingford, J. M., Thomas, H. B., Genomics UK Research Consortium, Douzgou, S., Beaman, G. M., Hobson, E., Prescott, K., O'Keefe, R. T., Newman, W. G. <strong>Expanding the genotypic spectrum of TXNL4A variants in Burn-McKeown syndrome.</strong> Clin. Genet. 101: 255-259, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34713892/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34713892</a>] [<a href="https://doi.org/10.1111/cge.14082" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34713892">Wood et al. (2022)</a> identified compound heterozygous mutations in the TXNL4A gene: a type 1 34-bp deletion in the promoter (<a href="#0001">611595.0001</a>) and a 2-bp deletion (c.93_94delCC, NM_006701) resulting in a frameshift and premature termination (His32ArgfsTer21). The frameshift variant was not present in gnomAD. The type 1 deletion was inherited from the mother and the 2-bp deletion from the father. The father, who had some mild features of BMKS, including possible choanal atresia and a flat malar region, had died of esophageal carcinoma, precluding further studies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34713892" 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 whole-exome sequencing in a boy (family 2) with Burn-McKeown syndrome (BMKS; <a href="/entry/608572">608572</a>), <a href="#8" class="mim-tip-reference" title="Wood, K. A., Ellingford, J. M., Thomas, H. B., Genomics UK Research Consortium, Douzgou, S., Beaman, G. M., Hobson, E., Prescott, K., O'Keefe, R. T., Newman, W. G. <strong>Expanding the genotypic spectrum of TXNL4A variants in Burn-McKeown syndrome.</strong> Clin. Genet. 101: 255-259, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34713892/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34713892</a>] [<a href="https://doi.org/10.1111/cge.14082" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34713892">Wood et al. (2022)</a> identified compound heterozygous mutations in the TXNL4A gene: a 34-bp deletion in the promoter (<a href="#0001">611595.0001</a>) and an acceptor splice site mutation (c.258-3C-G, NM_006701). The splice site mutation was not present in gnomAD. A minigene splicing assay showed that the c.258-3C-G variant and a previously described mutation affecting the adjacent nucleotide (c.258-2A-G) in a patient with BMKS caused skipping of the third and final exon of TXNL4A. The splice acceptor variant was maternally inherited and the type 1 34-bp deletion was paternally inherited. Both parents were unaffected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34713892" 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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Burn, J., McKeown, C., Wagget, J., Bray, R., Goodship, J.
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<strong>New dysmorphic syndrome with choanal atresia in siblings.</strong>
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Clin. Dysmorph. 1: 137-144, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1342861/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1342861</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1342861" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Hing, A. V., LeBlond, C., Sze, R. W., Starr, J. R., Monks, S., Parisi, M. A.
|
|
<strong>A novel oculo-oto-facial dysplasia in a native Alaskan community with autosomal recessive inheritance.</strong>
|
|
Am. J. Med. Genet. 140A: 804-812, 2006.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16523509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16523509</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16523509" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.31160" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="4" class="mim-anchor"></a>
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<a id="Jin2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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|
Jin, T., Guo, F., Wang, Y., Zhang, Y.-Z.
|
|
<strong>Identification of human dim1 as a peptidase with autocleavage activity.</strong>
|
|
Chem. Biol. Drug. Des. 68: 266-272, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17177886/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17177886</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17177886" 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/10.1111/j.1747-0285.2006.00447.x" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="5" class="mim-anchor"></a>
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<a id="Reuter1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Reuter, K., Nottrott, S., Fabrizio, P., Luhrmann, R., Ficner, R.
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|
<strong>Identification, characterization and crystal structure analysis of the human spliceosomal U5 snRNP-specific 15 kD protein.</strong>
|
|
J. Molec. Biol. 294: 515-525, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10610776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10610776</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10610776" 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/10.1006/jmbi.1999.3258" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="6" class="mim-anchor"></a>
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<a id="Wieczorek2014" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wieczorek, D., Newman, W. G., Wieland, T., Berulava, T., Kaffe, M., Falkenstein, D., Beetz, C., Graf, E., Schwarzmayr, T., Douzgou, S., Clayton-Smith, J., Daly, S. B., and 30 others.
|
|
<strong>Compound heterozygosity of low-frequency promoter deletions and rare loss-of-function mutations in TXNL4A causes Burn-McKeown syndrome.</strong>
|
|
Am. J. Hum. Genet. 95: 698-707, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25434003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25434003</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25434003[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=25434003" 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.2014.10.014" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="7" class="mim-anchor"></a>
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<a id="Wieczorek2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wieczorek, D., Teber, O. A., Lohmann, D., Gillessen-Kaesbach, G.
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<strong>Two brothers with Burn-McKeown syndrome.</strong>
|
|
Clin. Dysmorph. 12: 171-174, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14564154/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14564154</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14564154" 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/10.1097/01.mcd.0000072163.33788.c4" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="8" class="mim-anchor"></a>
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<a id="Wood2022" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wood, K. A., Ellingford, J. M., Thomas, H. B., Genomics UK Research Consortium, Douzgou, S., Beaman, G. M., Hobson, E., Prescott, K., O'Keefe, R. T., Newman, W. G.
|
|
<strong>Expanding the genotypic spectrum of TXNL4A variants in Burn-McKeown syndrome.</strong>
|
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Clin. Genet. 101: 255-259, 2022.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34713892/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34713892</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34713892" 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/10.1111/cge.14082" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="9" class="mim-anchor"></a>
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<a id="Zhang1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zhang, Y.-Z., Gould, K. L., Dunbrack, R. L., Jr., Cheng, H., Roder, H., Golemis, E. A.
|
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<strong>The evolutionarily conserved Dim1 protein defines a novel branch of the thioredoxin fold superfamily.</strong>
|
|
Physiol. Genomics 1: 109-118, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11015569/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11015569</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11015569" 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/10.1152/physiolgenomics.1999.1.3.109" target="_blank">Full Text</a>]
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</p>
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</div>
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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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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Sonja A. Rasmussen - updated : 08/03/2022
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Anne M. Stumpf - updated : 08/03/2022<br>Matthew B. Gross - updated : 04/06/2018<br>Marla J. F. O'Neill - updated : 1/5/2015
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Stefanie A. Nelson : 11/9/2007
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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="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 08/04/2022
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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alopez : 08/03/2022<br>alopez : 08/03/2022<br>alopez : 08/03/2022<br>alopez : 08/03/2022<br>carol : 01/23/2020<br>carol : 04/09/2018<br>mgross : 04/06/2018<br>carol : 10/20/2016<br>carol : 01/07/2015<br>mcolton : 1/5/2015<br>wwang : 12/27/2007<br>wwang : 11/9/2007<br>wwang : 11/9/2007
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</span>
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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 class="container visible-print-block">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 611595
|
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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THIOREDOXIN-LIKE 4A; TXNL4A
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<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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DIM1, S. POMBE, HOMOLOG OF; DIM1<br />
|
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U5 snRNP-SPECIFIC PROTEIN, 15-KD<br />
|
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U5-15KD
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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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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: TXNL4A</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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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 720640005;
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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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<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: 18q23
|
|
|
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Genomic coordinates <span class="small">(GRCh38)</span> : 18:79,970,813-80,033,936 </span>
|
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</em>
|
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</strong>
|
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<span class="small">(from NCBI)</span>
|
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</h4>
|
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<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
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<thead>
|
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<tr class="active">
|
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<th>
|
|
Location
|
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</th>
|
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<th>
|
|
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>
|
|
Inheritance
|
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</th>
|
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<th>
|
|
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">
|
|
18q23
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
Burn-McKeown syndrome
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
608572
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
3
|
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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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<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>TEXT</strong>
|
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</span>
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</h4>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Cloning and Expression</strong>
|
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</span>
|
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</h4>
|
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</div>
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<span class="mim-text-font">
|
|
<p>By SDS-PAGE of human 20S U5 snRNP, followed by EST database analysis, and PCR of a HeLa cell cDNA library, Reuter et al. (1999) cloned TXNL4A, which they called U5-15KD. The deduced protein contained 142 amino acids and contains a thioredoxin-like domain. TXNL4A shares 66% sequence identity with the S. cerevisiae homolog Dib1. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<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">
|
|
<p>Wood et al. (2022) determined that the TXNL4A promoter region consists of two 22-bp repeated motifs (RR1 and RR2) separated by a 12-bp spacer. They identified potential binding sites for 4 transcription factors, XBP1 (194355), c-JUN (see 165160), AHR/ARNT (see 600253), and ATF3 (603148). Dual luciferase assays demonstrated that RR1 and RR2 contain the critical nucleotides necessary for TXNL4A promoter activity and that RR1 and RR2 act independently and cumulatively to promote TXNL4A expression. </p><p>Wood et al. (2022) determined that the TXNL4A gene contains 3 exons. </p>
|
|
</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>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
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</h4>
|
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</div>
|
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|
|
<span class="mim-text-font">
|
|
<p>Gross (2018) mapped the TXNL4A gene to chromosome 18q23 based on an alignment of the TXNL4A sequence (GenBank AF146373) with the genomic sequence (GRCh38).</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>Biochemical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<span class="mim-text-font">
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<p><strong><em>Crystal Structure</em></strong></p><p>
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Reuter et al. (1999) analyzed the crystal structure of U5-15KD at 1.4-angstrom resolution and determined that it has a thioredoxin (TXN; 187700)-like fold with a 4-stranded beta-sheet composed of pairs of parallel and antiparallel strands flanked by 3 alpha-helices. Compared to human thioredoxin, U5-15KD contains an additional 37 amino acid residues. </p><p>Zhang et al. (1999) used protein-threading search algorithms and multidimensional NMR methods and also determined that the human DIM1 protein adopts a thioredoxin fold. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By genetic depletion of Dib1 in S. cerevisiae, Reuter et al. (1999) showed that Dib1 is strictly required for pre-mRNA splicing in vivo. </p><p>In E. coli overexpressing DIM1, Zhang et al. (1999) identified a cleaved form of human DIM1 (residues 1-128) truncated immediately after the predicted thioredoxin homology region. They showed that cleaved DIM1 induced lethality in a dominant-negative manner when expressed in S. pombe. By using conditional mutant S. pombe strains, they showed that cleaved DIM1 induced cell cycle arrest at G2 phase. Zhang et al. (1999) suggested that the short 14-amino acid C-terminal tail of DIM1 is an essential sequence. </p><p>Jin et al. (2006) expressed tagged DIM1 in E. coli and performed enzyme cleavage assays on the purified proteins. They found that DIM1 has peptidase activity and undergoes autocleavage. Protease inhibitors EDTA, chymostatin, and 6-aminohexanoic acid inhibited DIM1 cleavage, and the cleaved dominant-negative form of DIM1 retained the autocleavage activity of the full-length protein. </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 9 of 11 families with Burn-McKeown syndrome (BMKS; 608572), Wieczorek et al. (2014) identified biallelic mutations in the TXNL4A gene. Affected members in 8 families were compound heterozygous for a 34-bp deletion in the TXNL4A promoter (designated 'type 1;' 611595.0001) and a truncating point mutation (611595.0002-611595.0004) or another deletion (see, e.g., 611595.0005). In the ninth family, affected individuals were homozygous for an overlapping but different 34-bp TXNL4A promoter deletion (designated 'type 2;' 611595.0006). Functional analysis revealed that both promoter deletions result in reduced expression of TXNL4A; haplotype analysis was consistent with the promoter deletions occurring due to recurrent events rather than a founder effect. </p><p>Using whole-genome sequencing, Wood et al. (2022) identified compound heterozygous mutations in the TXNL4A gene in 2 patients with BMKS. Both patients carried the type 1 34-bp deletion in the promoter on one allele; on the other allele, one patient had a 2-bp deletion (c.93_94delCC; 611595.0007) and the other patient had a splice site mutation (c.258-3C-G; 611595.0008). A minigene splicing assay showed that the c.258-3C-G mutation and a previously described mutation in an adjacent nucleotide in a patient with BKMS (c.258-2A-G) caused skipping of the final exon of TXNL4A. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
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</span>
|
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<strong>8 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">
|
|
<strong>.0001 BURN-MCKEOWN SYNDROME</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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TXNL4A, 34-BP DEL, PROMOTER DELETION 1
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<br />
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SNP: rs535089924,
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gnomAD: rs535089924,
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ClinVar: RCV000149583, RCV000170535, RCV000170536, RCV000170538, RCV000170539, RCV000170540, RCV000170541, RCV000170542, RCV000170543, RCV002225453
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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 affected individuals from 8 families with Burn-McKeown syndrome (BMKS; 608572), including patients from 2 families originally reported by Burn et al. (1992) and the 2 German brothers reported by Wieczorek et al. (2003), Wieczorek et al. (2014) identified compound heterozygosity for a 34-bp deletion in the promoter of the TXNL4A gene (chr18:77,748,581-77,748,614del, GRCh37) and a truncating point mutation (611595.0002-611595.0004) or deletion involving TXNL4A (see, e.g., 611595.0005). In each family, the promoter deletion was present in heterozygosity in an unaffected parent. The promoter deletion was not found in the 1000 Genomes Project database; however, analysis of 3,165 population-based samples of German origin and 178 of South Asian origin revealed 45 heterozygous type 1 deletions and 1 homozygous type 1 deletion, for a German allele frequency of 0.76%. Haplotype analysis revealed that the promoter deletions were located on different haplotypes and thus most likely occurred due to recurrent events rather than a founder effect. In the family corresponding to cases 1 and 2 of Burn et al. (1992), the second mutation was a 1.235-Mb terminal deletion (del(18)(q23-qter): 76,841,645-78,077,248, GRCh37); an unrelated affected Vietnamese girl carried an almost identical 1.222-Mb deletion as her second mutation (del(18)(q23-qter): 76,854,774-78,077,248, GRCh37). In the female patient who was case 5 of Burn et al. (1992), the second mutation was a de novo 4.701-Mb terminal deletion on a ring chromosome 18 (46,XX,r(18)(p14q23)arr18q23: 73,376,178-78,077,248, GRCh37). Functional analysis in transfected HEK293 cells demonstrated that the wildtype promoter region enhanced luciferase expression 85-fold compared to control, whereas enhancer activity of the type 1 deletion was reduced by 59% compared to wildtype. Primer extension analysis provided further evidence that the deletion in the promoter region negatively affects transcription, since steady-state transcript levels of the allele carrying wildtype open reading frame (ORF) and the type 1 promoter deletion were reduced compared to transcript levels of the allele with mutant ORF and wildtype promoter. </p><p>Wood et al. (2022) identified putative binding sites for 4 transcription factors (XBP1, 194355; c-JUN, see 165160; AHR/ARNT, see 600253; and ATF3, 603148) within a repeat of a 22-bp motif (RR2) in the 34-bp type 1 deletion region. Deletion of RR2 reduced promoter activity to 45% of wildtype, the same as deletion of the full 34-bp type 1 region. </p>
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</span>
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</div>
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<div>
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<br />
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|
</div>
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</div>
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<div>
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<div>
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|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 BURN-MCKEOWN SYNDROME</strong>
|
|
</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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TXNL4A, GLU117TER
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<br />
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|
|
SNP: rs727502793,
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|
|
gnomAD: rs727502793,
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|
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|
|
ClinVar: RCV000149584, RCV003422037
|
|
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|
|
</span>
|
|
</div>
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|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 German brothers with Burn-McKeown syndrome (BMKS; 608572), originally reported by Wieczorek et al. (2003), Wieczorek et al. (2014) identified compound heterozygous mutations in the TXNL4A gene: a 34-bp deletion in the promoter (611595.0001), and a c.349G-T transversion in exon 3, resulting in a glu117-to-ter (E117X) substitution. The nonsense mutation, which was present in heterozygosity in healthy family members, was not found in the 1000 Genomes Project or dbSNP databases or in 3,000 in-house control exomes from individuals with unrelated diseases. </p>
|
|
</span>
|
|
</div>
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<div>
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|
<br />
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|
</div>
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</div>
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<div>
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 BURN-MCKEOWN SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
TXNL4A, GLN13TER
|
|
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|
|
<br />
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|
|
SNP: rs727502794,
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|
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|
|
ClinVar: RCV000149585
|
|
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|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 34-year-old Swiss man with Burn-McKeown syndrome (BMKS; 608572), who had bilateral choanal atresia and cleft lip/palate but no reported internal malformations, Wieczorek et al. (2014) identified compound heterozygous mutations in the TXNL4A gene: a 34-bp deletion in the promoter (611595.0001), and a c.37C-T transition in exon 1, resulting in a gln13-to-ter (Q13X) substitution. The nonsense mutation, which was present in heterozygosity in healthy family members, was not found in the 1000 Genomes Project or dbSNP databases or in 3,000 in-house control exomes from individuals with unrelated diseases. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 BURN-MCKEOWN SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TXNL4A, 1-BP DEL, 131T
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs727502795,
|
|
|
|
|
|
|
|
ClinVar: RCV000149586
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Pakistani girl with Burn-McKeown syndrome (BMKS; 608572), who had lower eyelid defects, membranous choanal atresia, cardiac defects, and significant hearing loss with reduced or absent cochlear nerves, Wieczorek et al. (2014) identified compound heterozygous mutations in the TXNL4A gene: a 34-bp deletion in the promoter (611595.0001), and a 1-bp deletion (c.131delT) in exon 1, resulting in a frameshift and a premature termination codon (Val44AlafsTer48). The 1-bp deletion, which was present in heterozygosity in healthy family members, was not found in the 1000 Genomes Project or dbSNP databases or in 3,000 in-house control exomes from individuals with unrelated diseases. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 BURN-MCKEOWN SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TXNL4A, EX3DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000149587
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 3.75-year-old French boy with Burn-McKeown syndrome (BMKS; 608572), who had lower eyelid defects, bilateral choanal atresia, and unilateral cleft lip but no reported internal malformations, Wieczorek et al. (2014) identified compound heterozygous mutations in the TXNL4A gene: a 34-bp deletion in the promoter (611595.0001) and deletion of exon 3. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 BURN-MCKEOWN SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TXNL4A, 34-BP DEL, PROMOTER DELETION 2
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000149588
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a large Native Alaskan pedigree with Burn-McKeown syndrome (BMKS; 608572), originally reported by Hing et al. (2006), Wieczorek et al. (2014) identified homozygosity for a 34-bp deletion in the promoter of the TXNL4A gene, comprising the proximal 33 bp of the 56-bp region, plus the preceding nucleotide (chr18:77,748,604-77,748,637del, GRCh37). This 34-bp 'type 2' promoter deletion overlapped but was different from the 34-bp 'type 1' promoter deletion (611595.0001). The mutation segregated with disease in the family; all heterozygous carriers appeared healthy. The type 2 promoter deletion was not found in the 1000 Genomes Project database; however, analysis of 3,165 population-based samples of German origin and 178 of South Asian origin revealed 1 heterozygous type 2 deletion. Functional analysis in transfected HEK293 cells demonstrated that the wildtype promoter region enhanced luciferase expression 85-fold compared to control, whereas enhancer activity of the type 2 deletion was reduced by 72% compared to wildtype. </p><p>Wood et al. (2022) identified 1 copy of a repeated 22-bp motif (RR1) in the 34-bp type 2 deletion region of the TXNL4A promoter. Deletion of RR1 reduced promoter activity to 54% of wildtype. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 BURN-MCKEOWN SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TXNL4A, 2-BP DEL, 93CC
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2145089648,
|
|
|
|
|
|
|
|
ClinVar: RCV002273877
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>By whole-genome sequencing in a woman (family 1) with Burn-McKeown syndrome (BMKS; 608572), Wood et al. (2022) identified compound heterozygous mutations in the TXNL4A gene: a type 1 34-bp deletion in the promoter (611595.0001) and a 2-bp deletion (c.93_94delCC, NM_006701) resulting in a frameshift and premature termination (His32ArgfsTer21). The frameshift variant was not present in gnomAD. The type 1 deletion was inherited from the mother and the 2-bp deletion from the father. The father, who had some mild features of BMKS, including possible choanal atresia and a flat malar region, had died of esophageal carcinoma, precluding further studies. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 BURN-MCKEOWN SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TXNL4A, IVS2, C-G, -3
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2145048234,
|
|
|
|
|
|
|
|
ClinVar: RCV002273878
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>By whole-exome sequencing in a boy (family 2) with Burn-McKeown syndrome (BMKS; 608572), Wood et al. (2022) identified compound heterozygous mutations in the TXNL4A gene: a 34-bp deletion in the promoter (611595.0001) and an acceptor splice site mutation (c.258-3C-G, NM_006701). The splice site mutation was not present in gnomAD. A minigene splicing assay showed that the c.258-3C-G variant and a previously described mutation affecting the adjacent nucleotide (c.258-2A-G) in a patient with BMKS caused skipping of the third and final exon of TXNL4A. The splice acceptor variant was maternally inherited and the type 1 34-bp deletion was paternally inherited. Both parents were unaffected. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
|
<br />
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</div>
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</div>
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</div>
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<div>
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|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
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|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Burn, J., McKeown, C., Wagget, J., Bray, R., Goodship, J.
|
|
<strong>New dysmorphic syndrome with choanal atresia in siblings.</strong>
|
|
Clin. Dysmorph. 1: 137-144, 1992.
|
|
|
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|
|
[PubMed: 1342861]
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</p>
|
|
</li>
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|
<li>
|
|
<p class="mim-text-font">
|
|
Gross, M. B.
|
|
<strong>Personal Communication.</strong>
|
|
Baltimore, Md. 4/6/2018.
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|
|
</p>
|
|
</li>
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|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hing, A. V., LeBlond, C., Sze, R. W., Starr, J. R., Monks, S., Parisi, M. A.
|
|
<strong>A novel oculo-oto-facial dysplasia in a native Alaskan community with autosomal recessive inheritance.</strong>
|
|
Am. J. Med. Genet. 140A: 804-812, 2006.
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[PubMed: 16523509]
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|
[Full Text: https://doi.org/10.1002/ajmg.a.31160]
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</p>
|
|
</li>
|
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|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jin, T., Guo, F., Wang, Y., Zhang, Y.-Z.
|
|
<strong>Identification of human dim1 as a peptidase with autocleavage activity.</strong>
|
|
Chem. Biol. Drug. Des. 68: 266-272, 2006.
|
|
|
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|
|
[PubMed: 17177886]
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|
|
[Full Text: https://doi.org/10.1111/j.1747-0285.2006.00447.x]
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
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