3267 lines
220 KiB
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3267 lines
220 KiB
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Entry
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- *612014 - TETRATRICOPEPTIDE REPEAT DOMAIN-CONTAINING PROTEIN 21B; TTC21B
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- OMIM
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<p>
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<span class="h4">*612014</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</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/612014">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000123607;t=ENST00000243344" 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=79809" 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=612014" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000123607;t=ENST00000243344" 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_024753,XM_006712761,XM_011511871,XM_011511872,XM_017004967,XM_047445870" 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_024753" 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=612014" 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=07752&isoform_id=07752_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/TTC21B" 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/16552892,33417188,34783528,39795245,62822201,76879711,116089292,119631726,119631727,158259345,193788400,313104038,578804925,767919830,767919832,1034616701,2217331105,2462577307,2462577309,2462577311" 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/Q7Z4L5" 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=79809" 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=ENSG00000123607;t=ENST00000243344" 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=TTC21B" 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=TTC21B" 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+79809" 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/TTC21B" 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:79809" 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/79809" 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=chr2&hgg_gene=ENST00000243344.8&hgg_start=165873362&hgg_end=165953776&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:25660" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:25660" 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://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=612014[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=612014[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/TTC21B/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000123607" 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=TTC21B" 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=TTC21B" 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=TTC21B" 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=TTC21B&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/PA134882767" 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:25660" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1920918" 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/TTC21B#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:1920918" 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/79809/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=79809" 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=WBGene00022696;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-031010-34" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://reactome.org/content/query?q=TTC21B&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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</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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612014
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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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TETRATRICOPEPTIDE REPEAT DOMAIN-CONTAINING PROTEIN 21B; TTC21B
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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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TETRATRICOPEPTIDE REPEAT-CONTAINING HEDGEHOG MODULATOR 1; THM1
|
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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=TTC21B" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">TTC21B</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/2/739?start=-3&limit=10&highlight=739">2q24.3</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr2:165873362-165953776&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'})">2:165,873,362-165,953,776</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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<span class="hidden-sm hidden-xs pull-right">
|
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<a href="/clinicalSynopsis/table?mimNumber=613820,613819" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
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</a>
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</span>
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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="2">
|
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<span class="mim-font">
|
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<a href="/geneMap/2/739?start=-3&limit=10&highlight=739">
|
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2q24.3
|
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</a>
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
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Nephronophthisis 12
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
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<a href="/entry/613820"> 613820 </a>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <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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<tr>
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<td>
|
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<span class="mim-font">
|
|
Short-rib thoracic dysplasia 4 with or without polydactyly
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</span>
|
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/613819"> 613819 </a>
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/612014" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/612014" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
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<p>The TTC21B gene encodes an axonemal protein required for retrograde intraflagellar transport and involved in ciliary function (<a href="#3" class="mim-tip-reference" title="Tran, P. V., Haycraft, C. J., Besschetnova, T. Y., Turbe-Doan, A., Stottmann, R. W., Herron, B. J., Chesebro, A. L., Qiu, H., Scherz, P. J., Shah, J. V., Yoder, B. K., Beier, D. R. <strong>THM1 negatively modulates mouse Sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia.</strong> Nature Genet. 40: 403-410, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18327258/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18327258</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18327258[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18327258">Tran et al., 2008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18327258" 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="#3" class="mim-tip-reference" title="Tran, P. V., Haycraft, C. J., Besschetnova, T. Y., Turbe-Doan, A., Stottmann, R. W., Herron, B. J., Chesebro, A. L., Qiu, H., Scherz, P. J., Shah, J. V., Yoder, B. K., Beier, D. R. <strong>THM1 negatively modulates mouse Sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia.</strong> Nature Genet. 40: 403-410, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18327258/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18327258</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18327258[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18327258">Tran et al. (2008)</a> isolated the TTC21B gene and determined that it encodes THM1, a 'tetratricopeptide repeat-containing hedgehog modulator-1,' which localizes to cilia. The deduced 1,317-amino acid protein has a molecular mass of approximately 150 kD and is predicted to contain 11 tetratricopeptide repeat (TPR) domains. <a href="#3" class="mim-tip-reference" title="Tran, P. V., Haycraft, C. J., Besschetnova, T. Y., Turbe-Doan, A., Stottmann, R. W., Herron, B. J., Chesebro, A. L., Qiu, H., Scherz, P. J., Shah, J. V., Yoder, B. K., Beier, D. R. <strong>THM1 negatively modulates mouse Sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia.</strong> Nature Genet. 40: 403-410, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18327258/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18327258</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18327258[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18327258">Tran et al. (2008)</a> found that the Ttc21b gene is responsible for the 'alien' (aln) locus in mouse (see ANIMAL MODEL). In normal embryonic mice at day 10.5, Ttc21b and Ttc21a (<a href="/entry/611430">611430</a>) were widely expressed, with more intense expression in the maxillary prominence, branchial arches, limb buds, somites, and spinal cord. Ttc21a encodes a protein that is 49% identical to THM1 and has a similar predicted protein structure. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18327258" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The TTC21B gene contains 29 exons (<a href="#1" class="mim-tip-reference" title="Davis, E. E., Zhang, Q., Liu, Q., Diplas, B. H., Davey, L. M., Hartley, J., Stoetzel, C., Szymanska, K., Ramaswami, G., Logan, C. V., Muzny, D. M., Young, A. C., and 36 others. <strong>TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum.</strong> Nature Genet. 43: 189-196, 2011. Note: Erratum: Nature Genet. 43: 499 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21258341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21258341</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21258341[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.756" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21258341">Davis et al., 2011</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21258341" 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>Given the role of Ttc21b in mutant 'alien' mice, which show ciliary defects, <a href="#1" class="mim-tip-reference" title="Davis, E. E., Zhang, Q., Liu, Q., Diplas, B. H., Davey, L. M., Hartley, J., Stoetzel, C., Szymanska, K., Ramaswami, G., Logan, C. V., Muzny, D. M., Young, A. C., and 36 others. <strong>TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum.</strong> Nature Genet. 43: 189-196, 2011. Note: Erratum: Nature Genet. 43: 499 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21258341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21258341</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21258341[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.756" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21258341">Davis et al. (2011)</a> examined the role of TTC21B in human ciliopathies. Among a clinically diverse cohort of 753 patients with some form of ciliopathy, they found that affected members of 4 families with nephronophthisis (NPHP12; <a href="/entry/613820">613820</a>) and 1 patient from 1 family with a more severe phenotype consistent with Jeune asphyxiating thoracic dystrophy (SRTD4; <a href="/entry/613819">613819</a>) were homozygous or compound heterozygous for mutations in the TTC21B gene (<a href="#0001">612014.0001</a>-<a href="#0003">612014.0003</a> and <a href="#0004">612014.0004</a>-<a href="#0005">612014.0005</a>, respectively). No clinical details were given on the patients, except that some with NPHP12 had early onset and an extrarenal phenotype. All of these mutations were demonstrated to be either null or hypomorphic alleles by in vivo and in vitro complementation studies in mutant zebrafish, mammalian cells, and rodent photoreceptor sensory cilia. In addition, heterozygous functionally pathogenic alleles were found in about 5% of the total cohort, including 3 unrelated patients with Joubert syndrome-11 (JBTS11), suggesting that TTC21B might be a common contributor to the total mutational load in ciliopathies. About one-third of the cases with heterozygous TTC21B alleles also had mutant trans alleles in 13 different known ciliopathy genes (see, e.g., BBS1, <a href="/entry/209901">209901</a>). The report demonstrated that genetic lesions can be both causally associated with diverse ciliopathies and interact in trans with other disease-causing genes, resulting in a broad range of phenotypes and a complex pattern of inheritance involving variation across multiple sites of the ciliary proteome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21258341" 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 a British adult and an 8-year-old Chinese child diagnosed with Jeune ATD, <a href="#2" class="mim-tip-reference" title="McInerney-Leo, A. M., Harris, J. E., Leo, P. J., Marshall, M. S., Gardiner, B., Kinning, E., Leong, H. Y., McKenzie, F., Ong, W. P., Vodopiutz, J., Wicking, C., Brown, M. A., Zankl, A., Duncan, E. L. <strong>Whole exome sequencing is an efficient, sensitive and specific method for determining the genetic cause of short-rib thoracic dystrophies.</strong> Clin. Genet. 88: 550-557, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25492405/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25492405</a>] [<a href="https://doi.org/10.1111/cge.12550" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25492405">McInerney-Leo et al. (2015)</a> performed whole-exome sequencing and identified biallelic mutations in the TTC21B gene (<a href="#0006">612014.0006</a>-<a href="#0008">612014.0008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25492405" 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="#3" class="mim-tip-reference" title="Tran, P. V., Haycraft, C. J., Besschetnova, T. Y., Turbe-Doan, A., Stottmann, R. W., Herron, B. J., Chesebro, A. L., Qiu, H., Scherz, P. J., Shah, J. V., Yoder, B. K., Beier, D. R. <strong>THM1 negatively modulates mouse Sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia.</strong> Nature Genet. 40: 403-410, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18327258/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18327258</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18327258[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18327258">Tran et al. (2008)</a> found that the Ttc21b gene is responsible for the 'alien' (aln) locus in mouse. Aln mutant cilia have bulb-like structures at their tips in which intraflagellar transport (IFT) proteins such as Ift88 (<a href="/entry/600595">600595</a>) are sequestered, characteristic of Chlamydomonas reinhardtii and Caenorhabditis elegans retrograde IFT mutants. RNA interference knockdown of Ttc21b in mouse intermedullary collecting duct cells expressing an Ift88-enhanced yellow fluorescent protein fusion recapitulated the aln-mutant cilial phenotype, and live imaging of these cells revealed impaired retrograde intraflagellar transport. In contrast to previously described IFT mutants, Smoothened (<a href="/entry/601500">601500</a>) and full-length glioblastoma (GLI; <a href="/entry/165220">165220</a>) proteins localize to aln-mutant cilia. <a href="#3" class="mim-tip-reference" title="Tran, P. V., Haycraft, C. J., Besschetnova, T. Y., Turbe-Doan, A., Stottmann, R. W., Herron, B. J., Chesebro, A. L., Qiu, H., Scherz, P. J., Shah, J. V., Yoder, B. K., Beier, D. R. <strong>THM1 negatively modulates mouse Sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia.</strong> Nature Genet. 40: 403-410, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18327258/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18327258</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18327258[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18327258">Tran et al. (2008)</a> hypothesized that the aln retrograde IFT defect causes sequestration of IFT proteins in aln-mutant cilia and leads to the overactivated Sonic hedgehog (SHH; <a href="/entry/600725">600725</a>) signaling phenotype. Specifically, the aln mutation uncouples the roles of anterograde and retrograde transport in Sonic hedgehog signaling, suggesting that anterograde IFT is required for GLI activation and that retrograde IFT modulates this event. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18327258" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000023924 OR RCV000681870 OR RCV000685092 OR RCV000763456 OR RCV000786982 OR RCV000857219 OR RCV001003236 OR RCV001074967 OR RCV001328175 OR RCV002251925 OR RCV004528134" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023924, RCV000681870, RCV000685092, RCV000763456, RCV000786982, RCV000857219, RCV001003236, RCV001074967, RCV001328175, RCV002251925, RCV004528134" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023924...</a>
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<p>In affected members of 2 unrelated consanguineous families with nephronophthisis-12 (NPHP12; <a href="/entry/613820">613820</a>), <a href="#1" class="mim-tip-reference" title="Davis, E. E., Zhang, Q., Liu, Q., Diplas, B. H., Davey, L. M., Hartley, J., Stoetzel, C., Szymanska, K., Ramaswami, G., Logan, C. V., Muzny, D. M., Young, A. C., and 36 others. <strong>TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum.</strong> Nature Genet. 43: 189-196, 2011. Note: Erratum: Nature Genet. 43: 499 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21258341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21258341</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21258341[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.756" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21258341">Davis et al. (2011)</a> identified a homozygous mutation in exon 6 of the TTC21B gene, resulting in a pro209-to-leu (P209L) substitution in a TPR domain. One family was of Portuguese and the other of Egyptian descent. The mutation was not found in 796 controls. In vitro and in vivo functional expression studies in mammalian cells and zebrafish indicated that the mutant protein was a hypomorphic allele. In 2 additional families with early-onset NPHP with extrarenal manifestations, the P209L allele was found in compound heterozygosity with another pathogenic TTC21B allele: a cys552-to-ter (C552X; <a href="#0002">612014.0002</a>) substitution in exon 13 and an A-to-G transition in intron 20 (<a href="#0003">612014.0003</a>), respectively. Both of the latter mutations were shown by expression studies to be functionally null alleles. Haplotype analysis indicated a founder effect for the P209L allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21258341" 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 NEPHRONOPHTHISIS 12</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">rs387907059 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387907059;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=rs387907059" 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=rs387907059" 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=RCV000023925" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023925" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023925</a>
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<p>For discussion of the cys552-to-ter (C552X) mutation in the TTC21B gene that was found in compound heterozygous state in patients with nephronophthisis-12 (NPHP12; <a href="/entry/613820">613820</a>) by <a href="#1" class="mim-tip-reference" title="Davis, E. E., Zhang, Q., Liu, Q., Diplas, B. H., Davey, L. M., Hartley, J., Stoetzel, C., Szymanska, K., Ramaswami, G., Logan, C. V., Muzny, D. M., Young, A. C., and 36 others. <strong>TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum.</strong> Nature Genet. 43: 189-196, 2011. Note: Erratum: Nature Genet. 43: 499 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21258341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21258341</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21258341[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.756" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21258341">Davis et al. (2011)</a>, see <a href="#0001">612014.0001</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21258341" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 NEPHRONOPHTHISIS 12</strong>
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TTC21B, IVS20AS, A-G, -2
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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> rs766132877 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs766132877;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/rs766132877?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=rs766132877" 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=rs766132877" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000023926 OR RCV000857220 OR RCV001535927 OR RCV001852034" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023926, RCV000857220, RCV001535927, RCV001852034" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023926...</a>
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<p>For discussion of the A-G transition in intron 20 of the TTC21B gene that was found in compound heterozygous state in patients with nephronophthisis-12 (NPHP12; <a href="/entry/613820">613820</a>) by <a href="#1" class="mim-tip-reference" title="Davis, E. E., Zhang, Q., Liu, Q., Diplas, B. H., Davey, L. M., Hartley, J., Stoetzel, C., Szymanska, K., Ramaswami, G., Logan, C. V., Muzny, D. M., Young, A. C., and 36 others. <strong>TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum.</strong> Nature Genet. 43: 189-196, 2011. Note: Erratum: Nature Genet. 43: 499 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21258341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21258341</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21258341[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.756" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21258341">Davis et al. (2011)</a>, see <a href="#0001">612014.0001</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21258341" 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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<span class="mim-font">
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<strong>.0004 SHORT-RIB THORACIC DYSPLASIA 4</strong>
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TTC21B, ARG411TER
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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> rs185089786 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs185089786;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/rs185089786?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=rs185089786" 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=rs185089786" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000023927 OR RCV000627256 OR RCV001857364" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023927, RCV000627256, RCV001857364" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023927...</a>
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<p>In a patient of northern European origin with a phenotype consistent with asphyxiating thoracic dystrophy (SRTD4; <a href="/entry/613819">613819</a>), <a href="#1" class="mim-tip-reference" title="Davis, E. E., Zhang, Q., Liu, Q., Diplas, B. H., Davey, L. M., Hartley, J., Stoetzel, C., Szymanska, K., Ramaswami, G., Logan, C. V., Muzny, D. M., Young, A. C., and 36 others. <strong>TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum.</strong> Nature Genet. 43: 189-196, 2011. Note: Erratum: Nature Genet. 43: 499 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21258341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21258341</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21258341[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.756" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21258341">Davis et al. (2011)</a> identified compound heterozygosity for 2 mutations in the TTC21B gene: an arg411-to-ter (R411X) substitution in exon 10 and a leu795-to-pro (L795P; <a href="#0005">612014.0005</a>) substitution in a TPR domain in exon 18. Neither mutation was seen in 796 controls. In vitro and in vivo functional expression studies in mammalian cells and zebrafish indicated that the L795P mutant protein was a hypomorphic allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21258341" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0005" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0005 SHORT-RIB THORACIC DYSPLASIA 4</strong>
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TTC21B, LEU795PRO
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387907060 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387907060;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=rs387907060" 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=rs387907060" 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=RCV000023928" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023928" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023928</a>
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<p>For discussion of the leu795-to-pro (L795P) mutation in the TTC21B gene that was found in compound heterozygous state in a patient with a phenotype consistent with asphyxiating thoracic dystrophy (SRTD4; <a href="/entry/613819">613819</a>) by <a href="#1" class="mim-tip-reference" title="Davis, E. E., Zhang, Q., Liu, Q., Diplas, B. H., Davey, L. M., Hartley, J., Stoetzel, C., Szymanska, K., Ramaswami, G., Logan, C. V., Muzny, D. M., Young, A. C., and 36 others. <strong>TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum.</strong> Nature Genet. 43: 189-196, 2011. Note: Erratum: Nature Genet. 43: 499 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21258341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21258341</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21258341[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.756" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21258341">Davis et al. (2011)</a>, see <a href="#0004">612014.0004</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21258341" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0006" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0006 SHORT-RIB THORACIC DYSPLASIA 4 WITHOUT POLYDACTYLY</strong>
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TTC21B, IVS3AS, A-G, -2
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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> rs760214276 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs760214276;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/rs760214276?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=rs760214276" 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=rs760214276" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a British adult (SKPD-203.3) with short-rib thoracic dysplasia without polydactyly (SRTD4; <a href="/entry/613819">613819</a>), <a href="#2" class="mim-tip-reference" title="McInerney-Leo, A. M., Harris, J. E., Leo, P. J., Marshall, M. S., Gardiner, B., Kinning, E., Leong, H. Y., McKenzie, F., Ong, W. P., Vodopiutz, J., Wicking, C., Brown, M. A., Zankl, A., Duncan, E. L. <strong>Whole exome sequencing is an efficient, sensitive and specific method for determining the genetic cause of short-rib thoracic dystrophies.</strong> Clin. Genet. 88: 550-557, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25492405/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25492405</a>] [<a href="https://doi.org/10.1111/cge.12550" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25492405">McInerney-Leo et al. (2015)</a> identified compound heterozygosity for mutations in the TTC21B gene: a splice site mutation in intron 3 (c.152-2A-G, NM_024753), and a c.3605T-C transition in exon 26, resulting in a leu1202-to-pro (L1202P; <a href="#0005">612014.0005</a>) substitution. Neither mutation was found in internal or public variant databases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25492405" 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">rs759086770 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs759086770;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=rs759086770" 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=rs759086770" 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=RCV000515826 OR RCV000656518" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000515826, RCV000656518" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000515826...</a>
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<p>For discussion of the c.3605T-C transition (c.3605T-C, NM_024753) in exon 26 of the TTC21B gene, resulting in a leu1202-to-pro (L1202P) substitution, that was found in compound heterozygous state in a British adult patient (SKPD-203.3) with short-rib thoracic dysplasia without polydactyly (SRTD4; <a href="/entry/613819">613819</a>) by <a href="#2" class="mim-tip-reference" title="McInerney-Leo, A. M., Harris, J. E., Leo, P. J., Marshall, M. S., Gardiner, B., Kinning, E., Leong, H. Y., McKenzie, F., Ong, W. P., Vodopiutz, J., Wicking, C., Brown, M. A., Zankl, A., Duncan, E. L. <strong>Whole exome sequencing is an efficient, sensitive and specific method for determining the genetic cause of short-rib thoracic dystrophies.</strong> Clin. Genet. 88: 550-557, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25492405/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25492405</a>] [<a href="https://doi.org/10.1111/cge.12550" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25492405">McInerney-Leo et al. (2015)</a>, see <a href="#0006">612014.0006</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25492405" 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">rs1553516241 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1553516241;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=rs1553516241" 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=rs1553516241" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In an 8-year-old Chinese patient (SKPD-208.3) with short-rib thoracic dysplasia with polydactyly (SRTD4; <a href="/entry/613819">613819</a>), <a href="#2" class="mim-tip-reference" title="McInerney-Leo, A. M., Harris, J. E., Leo, P. J., Marshall, M. S., Gardiner, B., Kinning, E., Leong, H. Y., McKenzie, F., Ong, W. P., Vodopiutz, J., Wicking, C., Brown, M. A., Zankl, A., Duncan, E. L. <strong>Whole exome sequencing is an efficient, sensitive and specific method for determining the genetic cause of short-rib thoracic dystrophies.</strong> Clin. Genet. 88: 550-557, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25492405/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25492405</a>] [<a href="https://doi.org/10.1111/cge.12550" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25492405">McInerney-Leo et al. (2015)</a> identified homozygosity for a 4-bp insertion (c.268_269insTAGA, NM_024753) in exon 4 of the TTC21B gene, causing a frameshift predicted to result in a premature termination codon (Glu90_Ala91insTer). The mutation was not found in internal or public variant databases. Two additional mutations in SRTD-associated genes were detected in heterozygosity in this patient, an R560L substitution in the DYNC2H1 gene (<a href="/entry/603297">603297</a>) and an L328F substitution in the EVC gene (<a href="/entry/604831">604831</a>); the authors noted that it was possible that these variants might modify the SRTD phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25492405" 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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Davis, E. E., Zhang, Q., Liu, Q., Diplas, B. H., Davey, L. M., Hartley, J., Stoetzel, C., Szymanska, K., Ramaswami, G., Logan, C. V., Muzny, D. M., Young, A. C., and 36 others.
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<strong>TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum.</strong>
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Nature Genet. 43: 189-196, 2011. Note: Erratum: Nature Genet. 43: 499 only, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21258341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21258341</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21258341[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=21258341" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng.756" target="_blank">Full Text</a>]
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McInerney-Leo, A. M., Harris, J. E., Leo, P. J., Marshall, M. S., Gardiner, B., Kinning, E., Leong, H. Y., McKenzie, F., Ong, W. P., Vodopiutz, J., Wicking, C., Brown, M. A., Zankl, A., Duncan, E. L.
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<strong>Whole exome sequencing is an efficient, sensitive and specific method for determining the genetic cause of short-rib thoracic dystrophies.</strong>
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Clin. Genet. 88: 550-557, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25492405/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25492405</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25492405" 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.12550" target="_blank">Full Text</a>]
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Tran, P. V., Haycraft, C. J., Besschetnova, T. Y., Turbe-Doan, A., Stottmann, R. W., Herron, B. J., Chesebro, A. L., Qiu, H., Scherz, P. J., Shah, J. V., Yoder, B. K., Beier, D. R.
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<strong>THM1 negatively modulates mouse Sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia.</strong>
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Nature Genet. 40: 403-410, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18327258/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18327258</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18327258[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=18327258" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng.105" target="_blank">Full Text</a>]
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mcolton : 06/15/2015<br>carol : 2/10/2014<br>mgross : 2/26/2013<br>carol : 2/6/2012<br>ckniffin : 2/6/2012<br>alopez : 8/24/2011<br>ckniffin : 8/18/2011<br>carol : 5/13/2011<br>carol : 3/22/2011<br>ckniffin : 3/22/2011<br>alopez : 10/24/2009<br>terry : 10/8/2008<br>alopez : 4/28/2008<br>alopez : 4/27/2008
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<div class="col-md-8 col-md-offset-1">
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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> 612014
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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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TETRATRICOPEPTIDE REPEAT DOMAIN-CONTAINING PROTEIN 21B; TTC21B
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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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<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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TETRATRICOPEPTIDE REPEAT-CONTAINING HEDGEHOG MODULATOR 1; THM1
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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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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: TTC21B</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>
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<em>
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Cytogenetic location: 2q24.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 2:165,873,362-165,953,776 </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>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="2">
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<span class="mim-font">
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2q24.3
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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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Nephronophthisis 12
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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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|
613820
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant; Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
|
|
Short-rib thoracic dysplasia 4 with or without polydactyly
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
|
613819
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</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>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The TTC21B gene encodes an axonemal protein required for retrograde intraflagellar transport and involved in ciliary function (Tran et al., 2008). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Tran et al. (2008) isolated the TTC21B gene and determined that it encodes THM1, a 'tetratricopeptide repeat-containing hedgehog modulator-1,' which localizes to cilia. The deduced 1,317-amino acid protein has a molecular mass of approximately 150 kD and is predicted to contain 11 tetratricopeptide repeat (TPR) domains. Tran et al. (2008) found that the Ttc21b gene is responsible for the 'alien' (aln) locus in mouse (see ANIMAL MODEL). In normal embryonic mice at day 10.5, Ttc21b and Ttc21a (611430) were widely expressed, with more intense expression in the maxillary prominence, branchial arches, limb buds, somites, and spinal cord. Ttc21a encodes a protein that is 49% identical to THM1 and has a similar predicted protein structure. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Gene Structure</strong>
|
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</span>
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</h4>
|
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</div>
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<span class="mim-text-font">
|
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<p>The TTC21B gene contains 29 exons (Davis et al., 2011). </p>
|
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</span>
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<div>
|
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<br />
|
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>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>Given the role of Ttc21b in mutant 'alien' mice, which show ciliary defects, Davis et al. (2011) examined the role of TTC21B in human ciliopathies. Among a clinically diverse cohort of 753 patients with some form of ciliopathy, they found that affected members of 4 families with nephronophthisis (NPHP12; 613820) and 1 patient from 1 family with a more severe phenotype consistent with Jeune asphyxiating thoracic dystrophy (SRTD4; 613819) were homozygous or compound heterozygous for mutations in the TTC21B gene (612014.0001-612014.0003 and 612014.0004-612014.0005, respectively). No clinical details were given on the patients, except that some with NPHP12 had early onset and an extrarenal phenotype. All of these mutations were demonstrated to be either null or hypomorphic alleles by in vivo and in vitro complementation studies in mutant zebrafish, mammalian cells, and rodent photoreceptor sensory cilia. In addition, heterozygous functionally pathogenic alleles were found in about 5% of the total cohort, including 3 unrelated patients with Joubert syndrome-11 (JBTS11), suggesting that TTC21B might be a common contributor to the total mutational load in ciliopathies. About one-third of the cases with heterozygous TTC21B alleles also had mutant trans alleles in 13 different known ciliopathy genes (see, e.g., BBS1, 209901). The report demonstrated that genetic lesions can be both causally associated with diverse ciliopathies and interact in trans with other disease-causing genes, resulting in a broad range of phenotypes and a complex pattern of inheritance involving variation across multiple sites of the ciliary proteome. </p><p>In a British adult and an 8-year-old Chinese child diagnosed with Jeune ATD, McInerney-Leo et al. (2015) performed whole-exome sequencing and identified biallelic mutations in the TTC21B gene (612014.0006-612014.0008). </p>
|
|
</span>
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<div>
|
|
<br />
|
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</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
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|
|
<span class="mim-text-font">
|
|
<p>Tran et al. (2008) found that the Ttc21b gene is responsible for the 'alien' (aln) locus in mouse. Aln mutant cilia have bulb-like structures at their tips in which intraflagellar transport (IFT) proteins such as Ift88 (600595) are sequestered, characteristic of Chlamydomonas reinhardtii and Caenorhabditis elegans retrograde IFT mutants. RNA interference knockdown of Ttc21b in mouse intermedullary collecting duct cells expressing an Ift88-enhanced yellow fluorescent protein fusion recapitulated the aln-mutant cilial phenotype, and live imaging of these cells revealed impaired retrograde intraflagellar transport. In contrast to previously described IFT mutants, Smoothened (601500) and full-length glioblastoma (GLI; 165220) proteins localize to aln-mutant cilia. Tran et al. (2008) hypothesized that the aln retrograde IFT defect causes sequestration of IFT proteins in aln-mutant cilia and leads to the overactivated Sonic hedgehog (SHH; 600725) signaling phenotype. Specifically, the aln mutation uncouples the roles of anterograde and retrograde transport in Sonic hedgehog signaling, suggesting that anterograde IFT is required for GLI activation and that retrograde IFT modulates this event. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>8 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 NEPHRONOPHTHISIS 12</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TTC21B, PRO209LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs140511594,
|
|
|
|
|
|
gnomAD: rs140511594,
|
|
|
|
|
|
ClinVar: RCV000023924, RCV000681870, RCV000685092, RCV000763456, RCV000786982, RCV000857219, RCV001003236, RCV001074967, RCV001328175, RCV002251925, RCV004528134
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of 2 unrelated consanguineous families with nephronophthisis-12 (NPHP12; 613820), Davis et al. (2011) identified a homozygous mutation in exon 6 of the TTC21B gene, resulting in a pro209-to-leu (P209L) substitution in a TPR domain. One family was of Portuguese and the other of Egyptian descent. The mutation was not found in 796 controls. In vitro and in vivo functional expression studies in mammalian cells and zebrafish indicated that the mutant protein was a hypomorphic allele. In 2 additional families with early-onset NPHP with extrarenal manifestations, the P209L allele was found in compound heterozygosity with another pathogenic TTC21B allele: a cys552-to-ter (C552X; 612014.0002) substitution in exon 13 and an A-to-G transition in intron 20 (612014.0003), respectively. Both of the latter mutations were shown by expression studies to be functionally null alleles. Haplotype analysis indicated a founder effect for the P209L allele. </p>
|
|
</span>
|
|
</div>
|
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|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 NEPHRONOPHTHISIS 12</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TTC21B, CYS552TER
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|
|
|
|
|
<br />
|
|
|
|
SNP: rs387907059,
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|
|
|
|
|
|
|
ClinVar: RCV000023925
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the cys552-to-ter (C552X) mutation in the TTC21B gene that was found in compound heterozygous state in patients with nephronophthisis-12 (NPHP12; 613820) by Davis et al. (2011), see 612014.0001. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 NEPHRONOPHTHISIS 12</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
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|
|
TTC21B, IVS20AS, A-G, -2
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|
|
|
|
|
<br />
|
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|
|
SNP: rs766132877,
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|
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gnomAD: rs766132877,
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|
|
|
|
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ClinVar: RCV000023926, RCV000857220, RCV001535927, RCV001852034
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the A-G transition in intron 20 of the TTC21B gene that was found in compound heterozygous state in patients with nephronophthisis-12 (NPHP12; 613820) by Davis et al. (2011), see 612014.0001. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
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|
|
</div>
|
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|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 SHORT-RIB THORACIC DYSPLASIA 4</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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<div>
|
|
<span class="mim-text-font">
|
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TTC21B, ARG411TER
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<br />
|
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|
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SNP: rs185089786,
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|
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gnomAD: rs185089786,
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|
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ClinVar: RCV000023927, RCV000627256, RCV001857364
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient of northern European origin with a phenotype consistent with asphyxiating thoracic dystrophy (SRTD4; 613819), Davis et al. (2011) identified compound heterozygosity for 2 mutations in the TTC21B gene: an arg411-to-ter (R411X) substitution in exon 10 and a leu795-to-pro (L795P; 612014.0005) substitution in a TPR domain in exon 18. Neither mutation was seen in 796 controls. In vitro and in vivo functional expression studies in mammalian cells and zebrafish indicated that the L795P mutant protein was a hypomorphic allele. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
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|
<div>
|
|
<br />
|
|
</div>
|
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|
|
</div>
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 SHORT-RIB THORACIC DYSPLASIA 4</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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|
|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
TTC21B, LEU795PRO
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|
|
|
|
|
<br />
|
|
|
|
SNP: rs387907060,
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|
|
|
|
|
|
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ClinVar: RCV000023928
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|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the leu795-to-pro (L795P) mutation in the TTC21B gene that was found in compound heterozygous state in a patient with a phenotype consistent with asphyxiating thoracic dystrophy (SRTD4; 613819) by Davis et al. (2011), see 612014.0004. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 SHORT-RIB THORACIC DYSPLASIA 4 WITHOUT POLYDACTYLY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TTC21B, IVS3AS, A-G, -2
|
|
|
|
|
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<br />
|
|
|
|
SNP: rs760214276,
|
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|
|
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gnomAD: rs760214276,
|
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|
|
|
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ClinVar: RCV000656517, RCV002534247
|
|
|
|
|
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</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a British adult (SKPD-203.3) with short-rib thoracic dysplasia without polydactyly (SRTD4; 613819), McInerney-Leo et al. (2015) identified compound heterozygosity for mutations in the TTC21B gene: a splice site mutation in intron 3 (c.152-2A-G, NM_024753), and a c.3605T-C transition in exon 26, resulting in a leu1202-to-pro (L1202P; 612014.0005) substitution. Neither mutation was found in internal or public variant databases. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
|
<br />
|
|
</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0007 SHORT-RIB THORACIC DYSPLASIA 4 WITHOUT POLYDACTYLY</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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TTC21B, LEU1202PRO
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<br />
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SNP: rs759086770,
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ClinVar: RCV000515826, RCV000656518
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</span>
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</div>
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<span class="mim-text-font">
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<p>For discussion of the c.3605T-C transition (c.3605T-C, NM_024753) in exon 26 of the TTC21B gene, resulting in a leu1202-to-pro (L1202P) substitution, that was found in compound heterozygous state in a British adult patient (SKPD-203.3) with short-rib thoracic dysplasia without polydactyly (SRTD4; 613819) by McInerney-Leo et al. (2015), see 612014.0006. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0008 SHORT-RIB THORACIC DYSPLASIA 4 WITH POLYDACTYLY</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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TTC21B, 4-BP INS, 268TAGA
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<br />
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SNP: rs1553516241,
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ClinVar: RCV000656519
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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 an 8-year-old Chinese patient (SKPD-208.3) with short-rib thoracic dysplasia with polydactyly (SRTD4; 613819), McInerney-Leo et al. (2015) identified homozygosity for a 4-bp insertion (c.268_269insTAGA, NM_024753) in exon 4 of the TTC21B gene, causing a frameshift predicted to result in a premature termination codon (Glu90_Ala91insTer). The mutation was not found in internal or public variant databases. Two additional mutations in SRTD-associated genes were detected in heterozygosity in this patient, an R560L substitution in the DYNC2H1 gene (603297) and an L328F substitution in the EVC gene (604831); the authors noted that it was possible that these variants might modify the SRTD phenotype. </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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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Davis, E. E., Zhang, Q., Liu, Q., Diplas, B. H., Davey, L. M., Hartley, J., Stoetzel, C., Szymanska, K., Ramaswami, G., Logan, C. V., Muzny, D. M., Young, A. C., and 36 others.
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<strong>TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum.</strong>
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Nature Genet. 43: 189-196, 2011. Note: Erratum: Nature Genet. 43: 499 only, 2011.
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[PubMed: 21258341]
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[Full Text: https://doi.org/10.1038/ng.756]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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McInerney-Leo, A. M., Harris, J. E., Leo, P. J., Marshall, M. S., Gardiner, B., Kinning, E., Leong, H. Y., McKenzie, F., Ong, W. P., Vodopiutz, J., Wicking, C., Brown, M. A., Zankl, A., Duncan, E. L.
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<strong>Whole exome sequencing is an efficient, sensitive and specific method for determining the genetic cause of short-rib thoracic dystrophies.</strong>
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Clin. Genet. 88: 550-557, 2015.
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[PubMed: 25492405]
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[Full Text: https://doi.org/10.1111/cge.12550]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Tran, P. V., Haycraft, C. J., Besschetnova, T. Y., Turbe-Doan, A., Stottmann, R. W., Herron, B. J., Chesebro, A. L., Qiu, H., Scherz, P. J., Shah, J. V., Yoder, B. K., Beier, D. R.
|
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<strong>THM1 negatively modulates mouse Sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia.</strong>
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Nature Genet. 40: 403-410, 2008.
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[PubMed: 18327258]
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[Full Text: https://doi.org/10.1038/ng.105]
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</p>
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</li>
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</ol>
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<div>
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<br />
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</div>
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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<span class="text-nowrap mim-text-font">
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Contributors:
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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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Marla J. F. O'Neill - updated : 06/18/2018<br>Cassandra L. Kniffin - updated : 3/22/2011
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</div>
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</div>
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<br />
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<span class="text-nowrap mim-text-font">
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Creation Date:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh : 4/27/2008
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</span>
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</div>
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Edit History:
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carol : 06/18/2018<br>mcolton : 06/15/2015<br>carol : 2/10/2014<br>mgross : 2/26/2013<br>carol : 2/6/2012<br>ckniffin : 2/6/2012<br>alopez : 8/24/2011<br>ckniffin : 8/18/2011<br>carol : 5/13/2011<br>carol : 3/22/2011<br>ckniffin : 3/22/2011<br>alopez : 10/24/2009<br>terry : 10/8/2008<br>alopez : 4/28/2008<br>alopez : 4/27/2008
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