3425 lines
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3425 lines
264 KiB
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Entry
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- *604934 - TUBULIN-SPECIFIC CHAPERONE E; TBCE
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- OMIM
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<p>
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<span class="h4">*604934</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<a href="#mapping">Mapping</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/604934">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<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=ENSG00000284770;t=ENST00000642610" 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=6905" 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=604934" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000284770;t=ENST00000642610" 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_001079515,NM_001287801,NM_001287802,NM_003193" 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_003193" 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=604934" 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=05381&isoform_id=05381_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/TBCE" 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/1465772,4507375,14250438,30583011,74762146,118442828,119590427,119590428,119590429,119590430,119590431,158258006,221041200,221042074,568215736,568215738" 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/Q15813" 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=6905" 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=ENSG00000284770;t=ENST00000642610" 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=TBCE" 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=TBCE" 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+6905" 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/TBCE" 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:6905" 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/6905" 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=chr1&hgg_gene=ENST00000645655.1&hgg_start=235367427&hgg_end=235452443&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:11582" 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://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=604934[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=604934[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000284770" 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=TBCE" 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=TBCE" 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=TBCE" 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=TBCE&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/PA36346" 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:11582" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0033055.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1917680" 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/TBCE#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:1917680" 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/6905/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=6905" 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=WBGene00019503;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-051030-120" 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">
|
|
<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=TBCE&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 1197148005<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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604934
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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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TUBULIN-SPECIFIC CHAPERONE E; TBCE
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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">
|
|
COFACTOR E
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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=TBCE" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">TBCE</a></em></strong>
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</span>
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</p>
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/1/1817?start=-3&limit=10&highlight=1817">1q42.3</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr1:235367427-235452443&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'})">1:235,367,427-235,452,443</a> </span>
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</em>
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</strong>
|
|
<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>
|
|
<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>
|
|
Phenotype
|
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<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=617207,241410,244460" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</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>
|
|
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>
|
|
</thead>
|
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<tbody>
|
|
|
|
<tr>
|
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<td rowspan="3">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/1/1817?start=-3&limit=10&highlight=1817">
|
|
1q42.3
|
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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">
|
|
Encephalopathy, progressive, with amyotrophy and optic atrophy
|
|
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/617207"> 617207 </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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|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
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</td>
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</tr>
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<tr>
|
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<td>
|
|
<span class="mim-font">
|
|
Hypoparathyroidism-retardation-dysmorphism syndrome
|
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|
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</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/241410"> 241410 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Kenny-Caffey syndrome, type 1
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/244460"> 244460 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
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|
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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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<p>The TBCE gene encodes one of several chaperone proteins required for the proper folding of alpha-tubulin subunits and the formation of alpha-beta-tubulin heterodimers (<a href="#5" class="mim-tip-reference" title="Parvari, R., Hershkovitz, E., Grossman, N., Gorodischer, R., Loeys, B., Zecic, A., Mortier, G., Gregory, S., Sharony, R., Kambouris, M., Sakati, N., Meyer, B. F., and 10 others. <strong>Mutation of TBCE causes hypoparathyroidism-retardation-dysmorphism and autosomal recessive Kenny-Caffey syndrome.</strong> Nature Genet. 32: 448-452, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12389028/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12389028</a>] [<a href="https://doi.org/10.1038/ng1012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12389028">Parvari et al., 2002</a>). See <a href="/entry/602971">602971</a> for further information. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12389028" 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>Proteins contain within their primary amino acid sequence information sufficient to dictate 3-dimensional structure. Proper folding of many proteins requires facilitation via interaction with a class of multisubunit toroidal complexes called chaperonins (<a href="#3" class="mim-tip-reference" title="Lewis, S. A., Tian, G., Vainberg, I. E., Cowan, N. J. <strong>Chaperonin-mediated folding of actin and tubulin.</strong> J. Cell Biol. 132: 1-4, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8567715/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8567715</a>] [<a href="https://doi.org/10.1083/jcb.132.1.1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8567715">Lewis et al., 1996</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8567715" 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="#13" class="mim-tip-reference" title="Tian, G., Huang, Y., Rommelaere, H., Vandekerckhove, J., Ampe, C., Cowan, N. J. <strong>Pathway leading to correctly folded beta-tubulin.</strong> Cell 86: 287-296, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8706133/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8706133</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80100-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8706133">Tian et al. (1996)</a> identified 3 novel proteins that participate in beta-tubulin folding. By fractionating crude tissue extracts and assaying the fractions in in vitro cytosolic chaperonin (c-cpn)-mediated folding reactions, they isolated cofactor E. Cofactor E performs the second step in the beta-tubulin folding process, interacting with the beta-tubulin-cofactor D intermediate. Cofactor E has an apparent molecular mass of 150 kD on a gel filtration column. Under denaturing conditions, cofactor E consists of a 60-kD peptide. The authors used partial peptide sequence data from purified cofactor E to isolate the corresponding cDNA. Cofactor E shares 30% amino acid identity with S. cerevisiae pac2, and has a short region showing homology to the microtubule-binding domain of CLIP-170 (<a href="/entry/179838">179838</a>), a microtubule-associated protein that links endocytic vesicles to microtubules. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8706133" 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 mice, <a href="#8" class="mim-tip-reference" title="Schaefer, M. K. E., Schmalbruch, H., Buhler, E., Lopez, C., Martin, N., Guenet, J.-L., Haase, G. <strong>Progressive motor neuronopathy: a critical role of the tubulin chaperone TBCE in axonal tubulin routing from the Golgi apparatus.</strong> J. Neurosci. 27: 8779-8789, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17699660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17699660</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17699660[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1523/JNEUROSCI.1599-07.2007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17699660">Schaefer et al. (2007)</a> found that Tbce was expressed in ventral horn motor neurons and in neurons of superficial dorsal horn layers in the soma, but not in the axons. Tbce expression was also found in Schwann cell bodies. In motor neurons, Tbce accumulated at the Golgi apparatus, where it was demonstrated to control axonal tubulin routing in motor neurons. <a href="#6" class="mim-tip-reference" title="Rak, K., Frenz, S., Radeloff, A., Groh, J., Jablonka, S., Martini, R., Hagen, R., Mlynski, R. <strong>Mutation of the TBCE gene causes disturbance of microtubules in the auditory nerve and cochlear outer hair cell degeneration accompanied by progressive hearing loss in the pmn/pmn mouse.</strong> Exp. Neurol. 250: 333-340, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24120439/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24120439</a>] [<a href="https://doi.org/10.1016/j.expneurol.2013.10.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24120439">Rak et al. (2013)</a> found that Tbce was selectively expressed in outer hair cells and inner pillar cells in the organ of Corti in the mouse ear. Tbce was not detected in inner hair cells, the auditory nerve, or in the spiral ganglia. The cells of the organ of Corti are polarized and highly dependent on tubulin structures. <a href="#9" class="mim-tip-reference" title="Schafer, M. K., Bellouze, S., Jacquier, A., Schaller, S., Richard, L., Mathis, S., Vallat, J.-M., Haase, G. <strong>Sensory neuropathy in progressive motor neuronopathy (pmn) mice is associated with defects in microtubule polymerization and axonal transport.</strong> Brain Path. 27: 459-471, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27488538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27488538</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27488538[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/10.1111/bpa.12422" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27488538">Schafer et al. (2017)</a> found expression of the Tbce gene in murine dorsal root ganglion neurons, and in certain brain regions including cortex, hippocampus, and brainstem. Tbce localized to the Golgi apparatus in dorsal root ganglion neurons. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17699660+27488538+24120439" 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>Since mutations in the TBCE gene have been found in both autosomal recessive Kenny-Caffey syndrome (<a href="/entry/244460">244460</a>) and Sanjad-Sakati syndrome (<a href="/entry/241410">241410</a>) (see later), both of which map to 1q43-q44, the TBCE gene must map to that region. The mouse Tbce gene maps to chromosome 13 (<a href="#10" class="mim-tip-reference" title="Schmalbruch, H. M. D., Jensen, H., Bjearg, M., Kamienniecka, Z., Kurland, L. B. S. <strong>A new mouse mutant with progressive motor neuronopathy.</strong> J. Neuropath. Exp. Neurol. 50: 192-204, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2022963/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2022963</a>] [<a href="https://doi.org/10.1097/00005072-199105000-00002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2022963">Schmalbruch et al., 1991</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2022963" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><strong><em>Hypoparathyroidism-Retardation-Dysmorphism Syndrome and Autosomal Recessive Kenny-Caffey Syndrome</em></strong></p><p>
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Hypoparathyroidism-retardation-dysmorphism syndrome (HRDS; <a href="/entry/241410">241410</a>), also known as the Sanjad-Sakati syndrome, is an autosomal recessive disorder of congenital hypoparathyroidism, mental retardation, facial dysmorphism, and extreme growth failure reported almost exclusively in Middle Eastern populations. A similar syndrome with the additional features of osteosclerosis and recurrent bacterial infections is the autosomal recessive Kenny-Caffey syndrome (KCS1; <a href="/entry/244460">244460</a>). Both disorders were mapped to 1q43-q44 and, despite the differences in clinical phenotype, were found to share an ancestral haplotype, suggesting a common founder mutation (<a href="#2" class="mim-tip-reference" title="Diaz, G. A., Gelb, B. D., Ali, F., Sakati, N., Sanjad, S., Meyer, B. F., Kambouris, M. <strong>Sanjad-Sakati and autosomal recessive Kenny-Caffey syndromes are allelic: evidence for an ancestral founder mutation and locus refinement.</strong> Am. J. Med. Genet. 85: 48-52, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10377012/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10377012</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(19990702)85:1<48::aid-ajmg9>3.0.co;2-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10377012">Diaz et al., 1999</a>). <a href="#5" class="mim-tip-reference" title="Parvari, R., Hershkovitz, E., Grossman, N., Gorodischer, R., Loeys, B., Zecic, A., Mortier, G., Gregory, S., Sharony, R., Kambouris, M., Sakati, N., Meyer, B. F., and 10 others. <strong>Mutation of TBCE causes hypoparathyroidism-retardation-dysmorphism and autosomal recessive Kenny-Caffey syndrome.</strong> Nature Genet. 32: 448-452, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12389028/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12389028</a>] [<a href="https://doi.org/10.1038/ng1012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12389028">Parvari et al. (2002)</a> refined the critical region on 1q to an interval of roughly 230 kb and identified deletion and truncation mutations of the TBCE gene in affected individuals (<a href="#0001">604934.0001</a>-<a href="#0003">604934.0003</a>). The vast majority of patients carried a recurrent 12-bp deletion (<a href="#0001">604934.0001</a>). Analysis of diseased fibroblasts and lymphoblastoid cells showed lower microtubule density at the microtubule-organizing center (MTOC) and perturbed microtubule polarity in diseased cells. Immunofluorescence and ultrastructural studies showed disturbances in subcellular organelles that require microtubules for membrane trafficking, such as the Golgi and late endosomal compartments. Thus, HRDS and KCS1 are chaperone diseases caused by genetic defect in the tubulin assembly pathway, and these findings established a potential connection between tubulin physiology and the development of the parathyroid. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12389028+10377012" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Progressive Encephalopathy with Amyotrophy and Optic Atrophy</em></strong></p><p>
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In 5 patients from 3 unrelated Italian families with progressive encephalopathy with amyotrophy and optic atrophy (PEAMO; <a href="/entry/617207">617207</a>), <a href="#11" class="mim-tip-reference" title="Sferra, A., Baillat, G., Rizza, T., Barresi, S., Flex, E., Tasca, G., D'Amico, A., Bellacchio, E., Ciolfi, A., Caputo, V., Cecchetti, S., Torella, A., and 14 others. <strong>TBCE mutations cause early-onset progressive encephalopathy with distal spinal muscular atrophy.</strong> Am. J. Hum. Genet. 99: 974-983, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27666369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27666369</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27666369[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.08.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27666369">Sferra et al. (2016)</a> identified a homozygous missense mutation in the TBCE gene (I155N; <a href="#0004">604934.0004</a>). The mutation in 2 families was found by whole-exome sequencing and confirmed by Sanger sequencing; the mutation in a pair of affected monozygotic twins in the third family was found by mutation scan of the TBCE gene. Another patient (patient 2518864) with the disorder was found to be compound heterozygous for the I155N mutation and a frameshift mutation (<a href="#0005">604934.0005</a>). The mutations segregated with the disorder in all families, and haplotype analysis of the families indicated a founder effect for I155N. Western blot analysis of patient fibroblasts showed significantly reduced amounts of mutant TBCE protein compared to controls, with lower levels in the patient with compound heterozygous mutations. RNA analysis of patient cells showed normal levels in the patient homozygous for I155N, but decreased amounts of RNA in the compound heterozygous patient, suggesting that the 1-bp deletion resulted in nonsense-mediated mRNA decay. Patient cells showed decreased levels of polymerized alpha-tubulin (see <a href="/entry/602529">602529</a>) and altered microtubule dynamics with decreased nucleation and markedly delayed microtubule repolymerization; microtubules were less abundant and strongly disorganized in both early and late stages of repolymerization, and there was loss of compaction in the Golgi apparatus. There was also abnormal mitotic morphology with abnormal mitotic spindles and disorganized microtubule arrangement. <a href="#11" class="mim-tip-reference" title="Sferra, A., Baillat, G., Rizza, T., Barresi, S., Flex, E., Tasca, G., D'Amico, A., Bellacchio, E., Ciolfi, A., Caputo, V., Cecchetti, S., Torella, A., and 14 others. <strong>TBCE mutations cause early-onset progressive encephalopathy with distal spinal muscular atrophy.</strong> Am. J. Hum. Genet. 99: 974-983, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27666369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27666369</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27666369[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.08.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27666369">Sferra et al. (2016)</a> concluded that the I155N allele is hypomorphic. The phenotype was similar to that of pmn/pmn mice who have a homozygous missense mutation in the Tbce gene (see ANIMAL MODEL). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27666369" 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>Mice that are homozygous with respect to the progressive motor neuronopathy (pmn) mutation on chromosome 13 develop a progressive caudiocranial degeneration of their motor axons from the age of 2 weeks and die 4 to 6 weeks after birth (<a href="#10" class="mim-tip-reference" title="Schmalbruch, H. M. D., Jensen, H., Bjearg, M., Kamienniecka, Z., Kurland, L. B. S. <strong>A new mouse mutant with progressive motor neuronopathy.</strong> J. Neuropath. Exp. Neurol. 50: 192-204, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2022963/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2022963</a>] [<a href="https://doi.org/10.1097/00005072-199105000-00002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2022963">Schmalbruch et al., 1991</a>). The mutation is fully penetrant and expressivity does not depend on the genetic background. <a href="#4" class="mim-tip-reference" title="Martin, N., Jaubert, J., Gounon, P., Salido, E., Haase, G., Szatanik, M., Guenet, J.-L. <strong>A missense mutation in Tbce causes progressive motor neuronopathy in mice.</strong> Nature Genet. 32: 443-447, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12389029/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12389029</a>] [<a href="https://doi.org/10.1038/ng1016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12389029">Martin et al. (2002)</a> identified the pmn mutation as a trp524-to-gly (W524G) substitution at the last residue of the Tbce protein that leads to decreased protein stability. Electron microscopy of the sciatic and phrenic nerves of affected mice showed a reduced number of microtubules, probably due to defective stabilization. Transgenic complementation with a wildtype Tbce cDNA restored a normal phenotype in mutant mice. The observations indicated that Tbce is critical for the maintenance of microtubules in mouse motor axons, and suggested that altered function of tubulin cofactors might be implicated in human motor neuron diseases. <a href="#1" class="mim-tip-reference" title="Bommel, H., Xie, G., Rossoll, W., Wiese, S., Jablonka, S., Boehm, T., Sendtner, M. <strong>Missense mutation in the tubulin-specific chaperone E (Tbce) gene in the mouse mutant progressive motor neuronopathy, a model of human motoneuron disease.</strong> J. Cell Biol. 159: 563-569, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12446740/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12446740</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12446740[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/10.1083/jcb.200208001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12446740">Bommel et al. (2002)</a> independently identified a point mutation resulting in the trp524-to-gly substitution in the Tbce protein in pmn mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12389029+12446740+2022963" 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>Homozygous pmn mice have a severe motor neuron disease characterized by motor axon dying back and progressive loss of motor units. In pmn mice, <a href="#8" class="mim-tip-reference" title="Schaefer, M. K. E., Schmalbruch, H., Buhler, E., Lopez, C., Martin, N., Guenet, J.-L., Haase, G. <strong>Progressive motor neuronopathy: a critical role of the tubulin chaperone TBCE in axonal tubulin routing from the Golgi apparatus.</strong> J. Neurosci. 27: 8779-8789, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17699660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17699660</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17699660[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1523/JNEUROSCI.1599-07.2007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17699660">Schaefer et al. (2007)</a> found that axonal microtubule loss in the phrenic and sciatic nerves first manifested distally and progressed proximally, in parallel with the axonal dying back neuronopathy. Studies of cultured pmn neurons showed loss of Tbce from the Golgi apparatus in motor neuron cells and in Schwann cells, microtubule loss resulting from defective axonal routing of tubulin from the Golgi, and impaired tubulin folding and dimerization. Similar results were found with knockdown of the Tbce gene in cultured motor neurons. The findings indicated that destabilization of Tbce in motor neurons is responsible for the axonal dying back process in pmn mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17699660" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Rak, K., Frenz, S., Radeloff, A., Groh, J., Jablonka, S., Martini, R., Hagen, R., Mlynski, R. <strong>Mutation of the TBCE gene causes disturbance of microtubules in the auditory nerve and cochlear outer hair cell degeneration accompanied by progressive hearing loss in the pmn/pmn mouse.</strong> Exp. Neurol. 250: 333-340, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24120439/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24120439</a>] [<a href="https://doi.org/10.1016/j.expneurol.2013.10.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24120439">Rak et al. (2013)</a> noted that homozygous pmn mice develop progressive hearing loss associated with cochlear dysfunction. Mutant mice had loss of outer hair cells due to apoptosis, as well as disturbance of tubulin structures in the auditory nerve. The findings indicated that tubulin is important for the correct function of the cochlear sensory epithelium. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24120439" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Schafer, M. K., Bellouze, S., Jacquier, A., Schaller, S., Richard, L., Mathis, S., Vallat, J.-M., Haase, G. <strong>Sensory neuropathy in progressive motor neuronopathy (pmn) mice is associated with defects in microtubule polymerization and axonal transport.</strong> Brain Path. 27: 459-471, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27488538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27488538</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27488538[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/10.1111/bpa.12422" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27488538">Schafer et al. (2017)</a> found that pmn mice also have evidence of sensory axon degeneration in addition to motor nerve axon degeneration. Sural nerves from mutant mice showed axonal abnormalities, including bead-like spheroids, suggestive of a multifocal degenerative process, as well as progressive loss of microtubules. Studies of dorsal root ganglion neurons showed that the pmn mutation impaired microtubule polymerization and microtubule-based axonal transport in these sensory cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27488538" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<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> rs767004810 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs767004810;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/rs767004810?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=rs767004810" 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=rs767004810" 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=RCV000005608 OR RCV000191990 OR RCV000224858 OR RCV003989279" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005608, RCV000191990, RCV000224858, RCV003989279" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005608...</a>
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<p><a href="#5" class="mim-tip-reference" title="Parvari, R., Hershkovitz, E., Grossman, N., Gorodischer, R., Loeys, B., Zecic, A., Mortier, G., Gregory, S., Sharony, R., Kambouris, M., Sakati, N., Meyer, B. F., and 10 others. <strong>Mutation of TBCE causes hypoparathyroidism-retardation-dysmorphism and autosomal recessive Kenny-Caffey syndrome.</strong> Nature Genet. 32: 448-452, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12389028/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12389028</a>] [<a href="https://doi.org/10.1038/ng1012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12389028">Parvari et al. (2002)</a> demonstrated homozygosity for a 12-bp deletion in the second coding exon of the TBCE gene in all Middle Eastern individuals with hypoparathyroidism-retardation-dysmorphism syndrome (HRDS; <a href="/entry/241410">241410</a>) whom they evaluated (more than 50). The deletion was not present in more than 350 control chromosomes from Arab individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12389028" 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>All the Middle Eastern subjects studied by <a href="#5" class="mim-tip-reference" title="Parvari, R., Hershkovitz, E., Grossman, N., Gorodischer, R., Loeys, B., Zecic, A., Mortier, G., Gregory, S., Sharony, R., Kambouris, M., Sakati, N., Meyer, B. F., and 10 others. <strong>Mutation of TBCE causes hypoparathyroidism-retardation-dysmorphism and autosomal recessive Kenny-Caffey syndrome.</strong> Nature Genet. 32: 448-452, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12389028/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12389028</a>] [<a href="https://doi.org/10.1038/ng1012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12389028">Parvari et al. (2002)</a> had the 12-bp deletion in the TBCE gene; however, the phenotype in 8 pedigrees with 13 affected individuals was that of autosomal recessive Kenny-Caffey syndrome (KCS1; <a href="/entry/244460">244460</a>), differing from the phenotype in HRDS families (17 Saudi pedigrees, 27 affected individuals; 9 Israeli pedigrees, 25 affected individuals) owing to the additional presence of medullary stenosis of the long bones, calvarial osteosclerosis, and susceptibility to bacterial infection. The presence of patchy osteosclerosis in the long bones of some Saudi patients with HRDS and deaths secondary to sepsis in some Israeli Bedouin individuals with HRDS suggested variable expression of these phenotypic features in a pedigree-specific fashion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12389028" 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 female infant, born of consanguineous Moroccan parents, with HRDS, <a href="#7" class="mim-tip-reference" title="Ratbi, I., Lyahyai, J., Kabiri, M., Banouar, M., Zerkaoui, M., Barkat, A., Sefiani, A. <strong>The Bedouin mutation c.155-166del of the TBCE gene in a patient with Sanjad-Sakati syndrome of Moroccan origin.</strong> Ann. Saudi Med. 35: 170-172, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26336027/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26336027</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26336027[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/10.5144/0256-4947.2015.170" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26336027">Ratbi et al. (2015)</a> identified homozygosity for the 12-bp deletion (c.155_166del12) that was previously found only in patients of Middle Eastern descent. The findings were consistent with the history of Arab migration to Morocco with the expansion of Islam to North Africa in the 7th century. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26336027" 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">rs1572324681 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1572324681;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=rs1572324681" 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=rs1572324681" 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=RCV000005610 OR RCV001390254" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005610, RCV001390254" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005610...</a>
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<p>In a Belgian pedigree in which 2 sibs manifested features typical of hypoparathyroidism-retardation-dysmorphism syndrome (HRDS; <a href="/entry/241410">241410</a>), <a href="#5" class="mim-tip-reference" title="Parvari, R., Hershkovitz, E., Grossman, N., Gorodischer, R., Loeys, B., Zecic, A., Mortier, G., Gregory, S., Sharony, R., Kambouris, M., Sakati, N., Meyer, B. F., and 10 others. <strong>Mutation of TBCE causes hypoparathyroidism-retardation-dysmorphism and autosomal recessive Kenny-Caffey syndrome.</strong> Nature Genet. 32: 448-452, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12389028/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12389028</a>] [<a href="https://doi.org/10.1038/ng1012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12389028">Parvari et al. (2002)</a> showed that the surviving sib was compound heterozygous for a 2-bp deletion (66delAG) in the first coding exon of the TBCE gene, resulting in a frameshift after residue 22 with termination at residue 48 (val23fs48Ter), and a 1113T-A transversion in exon 12 of the TBCE gene, resulting in a cys371-to-ter (C371X; <a href="#0003">604934.0003</a>) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12389028" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using in vitro tubulin folding assays, <a href="#12" class="mim-tip-reference" title="Tian, G., Huang, M. C., Parvari, R., Diaz, G. A., Cowan, N. J. <strong>Cryptic out-of-frame translational initiation of TBCE rescues tubulin formation in compound heterozygous HRD.</strong> Proc. Nat. Acad. Sci. 103: 13491-13496, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16938882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16938882</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16938882[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0602798103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16938882">Tian et al. (2006)</a> found that TBCE expressed from the 66delAG allele supported in vitro tubulin folding and enhanced TBCC (<a href="/entry/602971">602971</a>)- and TBCD (<a href="/entry/604649">604649</a>)-driven tubulin GAP activity in a manner similar to that of wildtype, whereas protein expressed from the C371X allele showed no folding greater than that of a parallel control without TBCE and had no GAP-enhancing ability. <a href="#12" class="mim-tip-reference" title="Tian, G., Huang, M. C., Parvari, R., Diaz, G. A., Cowan, N. J. <strong>Cryptic out-of-frame translational initiation of TBCE rescues tubulin formation in compound heterozygous HRD.</strong> Proc. Nat. Acad. Sci. 103: 13491-13496, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16938882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16938882</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16938882[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0602798103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16938882">Tian et al. (2006)</a> identified 3 out-of-frame AUG codons upstream of the 66delAG mutation and demonstrated the existence of cryptic translation initiation at each of them. <a href="#12" class="mim-tip-reference" title="Tian, G., Huang, M. C., Parvari, R., Diaz, G. A., Cowan, N. J. <strong>Cryptic out-of-frame translational initiation of TBCE rescues tubulin formation in compound heterozygous HRD.</strong> Proc. Nat. Acad. Sci. 103: 13491-13496, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16938882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16938882</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16938882[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0602798103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16938882">Tian et al. (2006)</a> concluded that these cryptically initiated functional polypeptides explain the survival of affected individuals homozygous for mutated alleles that apparently lack the capacity to make functional TBCE. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16938882" 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 HYPOPARATHYROIDISM-RETARDATION-DYSMORPHISM SYNDROME</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908384 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908384;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=rs121908384" 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=rs121908384" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>For discussion of the cys371-to-ter (C371X) mutation in the TBCE gene that was found in compound heterozygosity in a Belgian patient with hypoparathyroidism-retardation-dysmorphism syndrome (HRDS; <a href="/entry/241410">241410</a>) by <a href="#5" class="mim-tip-reference" title="Parvari, R., Hershkovitz, E., Grossman, N., Gorodischer, R., Loeys, B., Zecic, A., Mortier, G., Gregory, S., Sharony, R., Kambouris, M., Sakati, N., Meyer, B. F., and 10 others. <strong>Mutation of TBCE causes hypoparathyroidism-retardation-dysmorphism and autosomal recessive Kenny-Caffey syndrome.</strong> Nature Genet. 32: 448-452, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12389028/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12389028</a>] [<a href="https://doi.org/10.1038/ng1012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12389028">Parvari et al. (2002)</a>, see <a href="#0002">604934.0002</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12389028" 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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TBCE, ILE155ASN (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs780472451;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs780472451</a>)
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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> rs780472451 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs780472451;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/rs780472451?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=rs780472451" 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=rs780472451" 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=RCV000412509 OR RCV001569082" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000412509, RCV001569082" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000412509...</a>
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<p>In 5 patients from 3 unrelated families originating from the same region in Southern Italy with progressive encephalopathy with amyotrophy and optic atrophy (PEAMO; <a href="/entry/617207">617207</a>), <a href="#11" class="mim-tip-reference" title="Sferra, A., Baillat, G., Rizza, T., Barresi, S., Flex, E., Tasca, G., D'Amico, A., Bellacchio, E., Ciolfi, A., Caputo, V., Cecchetti, S., Torella, A., and 14 others. <strong>TBCE mutations cause early-onset progressive encephalopathy with distal spinal muscular atrophy.</strong> Am. J. Hum. Genet. 99: 974-983, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27666369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27666369</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27666369[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.08.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27666369">Sferra et al. (2016)</a> identified a homozygous c.464T-A transversion (c.464T-A, NM_001079515.2) in the TBCE gene resulting in an ile155-to-asn (I155N) substitution at a highly conserved residue in the LRR domain. The mutation was noted in the text as c.464T-A, although in most of the sections of Table 1 it was referred to as c.463T-A. The mutation in 2 families was found by whole-exome sequencing and confirmed by Sanger sequencing; the mutation in a pair of affected monozygotic twins in the third family was found by mutation scan of the TBCE gene. Another patient (2518864) with the disorder was found to be compound heterozygous for the I155N mutation and a 1-bp deletion (c.1076delC; <a href="#0005">604934.0005</a>), resulting in a frameshift and premature termination (Leu360Ter). The mutations segregated with the disorder in all families. Both mutations were found at a low frequency in the dbSNP and ExAC databases: the frequency in ExAC was 0.000008 for I155N and 0.00002 for c.1076delC. Haplotype analysis of the families indicated a founder effect for I155N, although that variant was not found in 400 control individuals from the same geographic region near Naples. Western blot analysis of patient fibroblasts showed significantly reduced amounts of mutant TBCE protein compared to controls, with lower levels in the patient with compound heterozygous mutations. RNA analysis of patient cells showed normal levels in the patient homozygous for I155N, but decreased amounts of RNA in the compound heterozygous patient, suggesting that the 1-bp deletion resulted in nonsense-mediated mRNA decay. Patient cells showed decreased levels of polymerized alpha-tubulin and altered microtubule dynamics with decreased nucleation and markedly delayed microtubule repolymerization; microtubules were less abundant and strongly disorganized in both early and late stages of repolymerization, and there was loss of compaction in the Golgi apparatus. There was also abnormal mitotic morphology with abnormal mitotic spindles and disorganized microtubule arrangement. <a href="#11" class="mim-tip-reference" title="Sferra, A., Baillat, G., Rizza, T., Barresi, S., Flex, E., Tasca, G., D'Amico, A., Bellacchio, E., Ciolfi, A., Caputo, V., Cecchetti, S., Torella, A., and 14 others. <strong>TBCE mutations cause early-onset progressive encephalopathy with distal spinal muscular atrophy.</strong> Am. J. Hum. Genet. 99: 974-983, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27666369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27666369</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27666369[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.08.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27666369">Sferra et al. (2016)</a> concluded that the 155N allele is hypomorphic. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27666369" 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=RCV000412635 OR RCV002298580 OR RCV003558367" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000412635, RCV002298580, RCV003558367" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000412635...</a>
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<p>For discussion of the 1-bp deletion (c.1076delC, NM_001079515.2) in the TBCE gene, resulting in a frameshift and premature termination (Leu360Ter), that was found in compound heterozygous state in a patient with progressive encephalopathy with amyotrophy and optic atrophy (PEAMO; <a href="/entry/617207">617207</a>) by <a href="#11" class="mim-tip-reference" title="Sferra, A., Baillat, G., Rizza, T., Barresi, S., Flex, E., Tasca, G., D'Amico, A., Bellacchio, E., Ciolfi, A., Caputo, V., Cecchetti, S., Torella, A., and 14 others. <strong>TBCE mutations cause early-onset progressive encephalopathy with distal spinal muscular atrophy.</strong> Am. J. Hum. Genet. 99: 974-983, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27666369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27666369</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27666369[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.08.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27666369">Sferra et al. (2016)</a>, see <a href="#0004">604934.0004</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27666369" 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>Missense mutation in the tubulin-specific chaperone E (Tbce) gene in the mouse mutant progressive motor neuronopathy, a model of human motoneuron disease.</strong>
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J. Cell Biol. 159: 563-569, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12446740/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12446740</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12446740[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=12446740" 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/10.1083/jcb.200208001" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/(sici)1096-8628(19990702)85:1<48::aid-ajmg9>3.0.co;2-y" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1083/jcb.132.1.1" target="_blank">Full Text</a>]
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<strong>A missense mutation in Tbce causes progressive motor neuronopathy in mice.</strong>
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[<a href="https://doi.org/10.1038/ng1016" target="_blank">Full Text</a>]
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<a id="Parvari2002" class="mim-anchor"></a>
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Parvari, R., Hershkovitz, E., Grossman, N., Gorodischer, R., Loeys, B., Zecic, A., Mortier, G., Gregory, S., Sharony, R., Kambouris, M., Sakati, N., Meyer, B. F., and 10 others.
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<strong>Mutation of TBCE causes hypoparathyroidism-retardation-dysmorphism and autosomal recessive Kenny-Caffey syndrome.</strong>
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Nature Genet. 32: 448-452, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12389028/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12389028</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12389028" 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/ng1012" target="_blank">Full Text</a>]
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Rak, K., Frenz, S., Radeloff, A., Groh, J., Jablonka, S., Martini, R., Hagen, R., Mlynski, R.
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<strong>Mutation of the TBCE gene causes disturbance of microtubules in the auditory nerve and cochlear outer hair cell degeneration accompanied by progressive hearing loss in the pmn/pmn mouse.</strong>
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Exp. Neurol. 250: 333-340, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24120439/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24120439</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24120439" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.expneurol.2013.10.007" target="_blank">Full Text</a>]
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<a id="Ratbi2015" class="mim-anchor"></a>
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Ratbi, I., Lyahyai, J., Kabiri, M., Banouar, M., Zerkaoui, M., Barkat, A., Sefiani, A.
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<strong>The Bedouin mutation c.155-166del of the TBCE gene in a patient with Sanjad-Sakati syndrome of Moroccan origin.</strong>
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Ann. Saudi Med. 35: 170-172, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26336027/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26336027</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26336027[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=26336027" 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/10.5144/0256-4947.2015.170" target="_blank">Full Text</a>]
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<a id="Schaefer2007" class="mim-anchor"></a>
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Schaefer, M. K. E., Schmalbruch, H., Buhler, E., Lopez, C., Martin, N., Guenet, J.-L., Haase, G.
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<strong>Progressive motor neuronopathy: a critical role of the tubulin chaperone TBCE in axonal tubulin routing from the Golgi apparatus.</strong>
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J. Neurosci. 27: 8779-8789, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17699660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17699660</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17699660[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=17699660" 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/10.1523/JNEUROSCI.1599-07.2007" target="_blank">Full Text</a>]
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<a id="Schafer2017" class="mim-anchor"></a>
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Schafer, M. K., Bellouze, S., Jacquier, A., Schaller, S., Richard, L., Mathis, S., Vallat, J.-M., Haase, G.
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<strong>Sensory neuropathy in progressive motor neuronopathy (pmn) mice is associated with defects in microtubule polymerization and axonal transport.</strong>
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Brain Path. 27: 459-471, 2017.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27488538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27488538</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27488538[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=27488538" 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/bpa.12422" target="_blank">Full Text</a>]
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<a id="10" class="mim-anchor"></a>
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<a id="Schmalbruch1991" class="mim-anchor"></a>
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Schmalbruch, H. M. D., Jensen, H., Bjearg, M., Kamienniecka, Z., Kurland, L. B. S.
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<strong>A new mouse mutant with progressive motor neuronopathy.</strong>
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J. Neuropath. Exp. Neurol. 50: 192-204, 1991.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2022963/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2022963</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2022963" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1097/00005072-199105000-00002" target="_blank">Full Text</a>]
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<a id="Sferra2016" class="mim-anchor"></a>
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Sferra, A., Baillat, G., Rizza, T., Barresi, S., Flex, E., Tasca, G., D'Amico, A., Bellacchio, E., Ciolfi, A., Caputo, V., Cecchetti, S., Torella, A., and 14 others.
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<strong>TBCE mutations cause early-onset progressive encephalopathy with distal spinal muscular atrophy.</strong>
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Am. J. Hum. Genet. 99: 974-983, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27666369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27666369</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27666369[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=27666369" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ajhg.2016.08.006" target="_blank">Full Text</a>]
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Tian, G., Huang, M. C., Parvari, R., Diaz, G. A., Cowan, N. J.
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<strong>Cryptic out-of-frame translational initiation of TBCE rescues tubulin formation in compound heterozygous HRD.</strong>
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Proc. Nat. Acad. Sci. 103: 13491-13496, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16938882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16938882</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16938882[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=16938882" 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/10.1073/pnas.0602798103" target="_blank">Full Text</a>]
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Tian, G., Huang, Y., Rommelaere, H., Vandekerckhove, J., Ampe, C., Cowan, N. J.
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<strong>Pathway leading to correctly folded beta-tubulin.</strong>
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Cell 86: 287-296, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8706133/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8706133</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8706133" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0092-8674(00)80100-2" target="_blank">Full Text</a>]
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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Cassandra L. Kniffin - updated : 11/17/2016
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 10/4/2006<br>Cassandra L. Kniffin - updated : 4/2/2003<br>Victor A. McKusick - updated : 10/23/2002
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Stefanie A. Nelson : 5/9/2000
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carol : 07/17/2023<br>alopez : 07/14/2023<br>carol : 06/13/2017<br>alopez : 11/29/2016<br>ckniffin : 11/17/2016<br>carol : 09/30/2016<br>carol : 09/28/2015<br>carol : 7/26/2007<br>wwang : 10/10/2006<br>terry : 10/4/2006<br>ckniffin : 4/2/2003<br>alopez : 11/5/2002<br>alopez : 10/25/2002<br>alopez : 10/25/2002<br>alopez : 10/24/2002<br>terry : 10/23/2002<br>terry : 10/23/2002<br>alopez : 5/9/2000
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<h3>
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<span class="mim-font">
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<strong>*</strong> 604934
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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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TUBULIN-SPECIFIC CHAPERONE E; TBCE
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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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<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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COFACTOR E
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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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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: TBCE</em></strong>
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</span>
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</p>
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</div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 1197148005;
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</p>
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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: 1q42.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 1:235,367,427-235,452,443 </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="3">
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<span class="mim-font">
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1q42.3
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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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Encephalopathy, progressive, with amyotrophy and optic atrophy
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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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617207
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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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<tr>
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<td>
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<span class="mim-font">
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Hypoparathyroidism-retardation-dysmorphism syndrome
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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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241410
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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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<tr>
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<td>
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<span class="mim-font">
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Kenny-Caffey syndrome, type 1
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</span>
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</td>
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<td>
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<span class="mim-font">
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244460
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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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<br />
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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 TBCE gene encodes one of several chaperone proteins required for the proper folding of alpha-tubulin subunits and the formation of alpha-beta-tubulin heterodimers (Parvari et al., 2002). See 602971 for further information. </p><p>Proteins contain within their primary amino acid sequence information sufficient to dictate 3-dimensional structure. Proper folding of many proteins requires facilitation via interaction with a class of multisubunit toroidal complexes called chaperonins (Lewis et al., 1996). </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>Tian et al. (1996) identified 3 novel proteins that participate in beta-tubulin folding. By fractionating crude tissue extracts and assaying the fractions in in vitro cytosolic chaperonin (c-cpn)-mediated folding reactions, they isolated cofactor E. Cofactor E performs the second step in the beta-tubulin folding process, interacting with the beta-tubulin-cofactor D intermediate. Cofactor E has an apparent molecular mass of 150 kD on a gel filtration column. Under denaturing conditions, cofactor E consists of a 60-kD peptide. The authors used partial peptide sequence data from purified cofactor E to isolate the corresponding cDNA. Cofactor E shares 30% amino acid identity with S. cerevisiae pac2, and has a short region showing homology to the microtubule-binding domain of CLIP-170 (179838), a microtubule-associated protein that links endocytic vesicles to microtubules. </p><p>In mice, Schaefer et al. (2007) found that Tbce was expressed in ventral horn motor neurons and in neurons of superficial dorsal horn layers in the soma, but not in the axons. Tbce expression was also found in Schwann cell bodies. In motor neurons, Tbce accumulated at the Golgi apparatus, where it was demonstrated to control axonal tubulin routing in motor neurons. Rak et al. (2013) found that Tbce was selectively expressed in outer hair cells and inner pillar cells in the organ of Corti in the mouse ear. Tbce was not detected in inner hair cells, the auditory nerve, or in the spiral ganglia. The cells of the organ of Corti are polarized and highly dependent on tubulin structures. Schafer et al. (2017) found expression of the Tbce gene in murine dorsal root ganglion neurons, and in certain brain regions including cortex, hippocampus, and brainstem. Tbce localized to the Golgi apparatus in dorsal root ganglion neurons. </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>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Since mutations in the TBCE gene have been found in both autosomal recessive Kenny-Caffey syndrome (244460) and Sanjad-Sakati syndrome (241410) (see later), both of which map to 1q43-q44, the TBCE gene must map to that region. The mouse Tbce gene maps to chromosome 13 (Schmalbruch et al., 1991). </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><strong><em>Hypoparathyroidism-Retardation-Dysmorphism Syndrome and Autosomal Recessive Kenny-Caffey Syndrome</em></strong></p><p>
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Hypoparathyroidism-retardation-dysmorphism syndrome (HRDS; 241410), also known as the Sanjad-Sakati syndrome, is an autosomal recessive disorder of congenital hypoparathyroidism, mental retardation, facial dysmorphism, and extreme growth failure reported almost exclusively in Middle Eastern populations. A similar syndrome with the additional features of osteosclerosis and recurrent bacterial infections is the autosomal recessive Kenny-Caffey syndrome (KCS1; 244460). Both disorders were mapped to 1q43-q44 and, despite the differences in clinical phenotype, were found to share an ancestral haplotype, suggesting a common founder mutation (Diaz et al., 1999). Parvari et al. (2002) refined the critical region on 1q to an interval of roughly 230 kb and identified deletion and truncation mutations of the TBCE gene in affected individuals (604934.0001-604934.0003). The vast majority of patients carried a recurrent 12-bp deletion (604934.0001). Analysis of diseased fibroblasts and lymphoblastoid cells showed lower microtubule density at the microtubule-organizing center (MTOC) and perturbed microtubule polarity in diseased cells. Immunofluorescence and ultrastructural studies showed disturbances in subcellular organelles that require microtubules for membrane trafficking, such as the Golgi and late endosomal compartments. Thus, HRDS and KCS1 are chaperone diseases caused by genetic defect in the tubulin assembly pathway, and these findings established a potential connection between tubulin physiology and the development of the parathyroid. </p><p><strong><em>Progressive Encephalopathy with Amyotrophy and Optic Atrophy</em></strong></p><p>
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In 5 patients from 3 unrelated Italian families with progressive encephalopathy with amyotrophy and optic atrophy (PEAMO; 617207), Sferra et al. (2016) identified a homozygous missense mutation in the TBCE gene (I155N; 604934.0004). The mutation in 2 families was found by whole-exome sequencing and confirmed by Sanger sequencing; the mutation in a pair of affected monozygotic twins in the third family was found by mutation scan of the TBCE gene. Another patient (patient 2518864) with the disorder was found to be compound heterozygous for the I155N mutation and a frameshift mutation (604934.0005). The mutations segregated with the disorder in all families, and haplotype analysis of the families indicated a founder effect for I155N. Western blot analysis of patient fibroblasts showed significantly reduced amounts of mutant TBCE protein compared to controls, with lower levels in the patient with compound heterozygous mutations. RNA analysis of patient cells showed normal levels in the patient homozygous for I155N, but decreased amounts of RNA in the compound heterozygous patient, suggesting that the 1-bp deletion resulted in nonsense-mediated mRNA decay. Patient cells showed decreased levels of polymerized alpha-tubulin (see 602529) and altered microtubule dynamics with decreased nucleation and markedly delayed microtubule repolymerization; microtubules were less abundant and strongly disorganized in both early and late stages of repolymerization, and there was loss of compaction in the Golgi apparatus. There was also abnormal mitotic morphology with abnormal mitotic spindles and disorganized microtubule arrangement. Sferra et al. (2016) concluded that the I155N allele is hypomorphic. The phenotype was similar to that of pmn/pmn mice who have a homozygous missense mutation in the Tbce gene (see ANIMAL MODEL). </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>Animal Model</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>Mice that are homozygous with respect to the progressive motor neuronopathy (pmn) mutation on chromosome 13 develop a progressive caudiocranial degeneration of their motor axons from the age of 2 weeks and die 4 to 6 weeks after birth (Schmalbruch et al., 1991). The mutation is fully penetrant and expressivity does not depend on the genetic background. Martin et al. (2002) identified the pmn mutation as a trp524-to-gly (W524G) substitution at the last residue of the Tbce protein that leads to decreased protein stability. Electron microscopy of the sciatic and phrenic nerves of affected mice showed a reduced number of microtubules, probably due to defective stabilization. Transgenic complementation with a wildtype Tbce cDNA restored a normal phenotype in mutant mice. The observations indicated that Tbce is critical for the maintenance of microtubules in mouse motor axons, and suggested that altered function of tubulin cofactors might be implicated in human motor neuron diseases. Bommel et al. (2002) independently identified a point mutation resulting in the trp524-to-gly substitution in the Tbce protein in pmn mice. </p><p>Homozygous pmn mice have a severe motor neuron disease characterized by motor axon dying back and progressive loss of motor units. In pmn mice, Schaefer et al. (2007) found that axonal microtubule loss in the phrenic and sciatic nerves first manifested distally and progressed proximally, in parallel with the axonal dying back neuronopathy. Studies of cultured pmn neurons showed loss of Tbce from the Golgi apparatus in motor neuron cells and in Schwann cells, microtubule loss resulting from defective axonal routing of tubulin from the Golgi, and impaired tubulin folding and dimerization. Similar results were found with knockdown of the Tbce gene in cultured motor neurons. The findings indicated that destabilization of Tbce in motor neurons is responsible for the axonal dying back process in pmn mice. </p><p>Rak et al. (2013) noted that homozygous pmn mice develop progressive hearing loss associated with cochlear dysfunction. Mutant mice had loss of outer hair cells due to apoptosis, as well as disturbance of tubulin structures in the auditory nerve. The findings indicated that tubulin is important for the correct function of the cochlear sensory epithelium. </p><p>Schafer et al. (2017) found that pmn mice also have evidence of sensory axon degeneration in addition to motor nerve axon degeneration. Sural nerves from mutant mice showed axonal abnormalities, including bead-like spheroids, suggestive of a multifocal degenerative process, as well as progressive loss of microtubules. Studies of dorsal root ganglion neurons showed that the pmn mutation impaired microtubule polymerization and microtubule-based axonal transport in these sensory cells. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>5 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 HYPOPARATHYROIDISM-RETARDATION-DYSMORPHISM SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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KENNY-CAFFEY SYNDROME, TYPE 1, INCLUDED
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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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TBCE, 12-BP DEL, NT155
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<br />
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SNP: rs767004810,
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gnomAD: rs767004810,
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ClinVar: RCV000005608, RCV000191990, RCV000224858, RCV003989279
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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>Parvari et al. (2002) demonstrated homozygosity for a 12-bp deletion in the second coding exon of the TBCE gene in all Middle Eastern individuals with hypoparathyroidism-retardation-dysmorphism syndrome (HRDS; 241410) whom they evaluated (more than 50). The deletion was not present in more than 350 control chromosomes from Arab individuals. </p><p>All the Middle Eastern subjects studied by Parvari et al. (2002) had the 12-bp deletion in the TBCE gene; however, the phenotype in 8 pedigrees with 13 affected individuals was that of autosomal recessive Kenny-Caffey syndrome (KCS1; 244460), differing from the phenotype in HRDS families (17 Saudi pedigrees, 27 affected individuals; 9 Israeli pedigrees, 25 affected individuals) owing to the additional presence of medullary stenosis of the long bones, calvarial osteosclerosis, and susceptibility to bacterial infection. The presence of patchy osteosclerosis in the long bones of some Saudi patients with HRDS and deaths secondary to sepsis in some Israeli Bedouin individuals with HRDS suggested variable expression of these phenotypic features in a pedigree-specific fashion. </p><p>In a female infant, born of consanguineous Moroccan parents, with HRDS, Ratbi et al. (2015) identified homozygosity for the 12-bp deletion (c.155_166del12) that was previously found only in patients of Middle Eastern descent. The findings were consistent with the history of Arab migration to Morocco with the expansion of Islam to North Africa in the 7th century. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 HYPOPARATHYROIDISM-RETARDATION-DYSMORPHISM SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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TBCE, 2-BP DEL, 66AG
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<br />
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SNP: rs1572324681,
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ClinVar: RCV000005610, RCV001390254
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a Belgian pedigree in which 2 sibs manifested features typical of hypoparathyroidism-retardation-dysmorphism syndrome (HRDS; 241410), Parvari et al. (2002) showed that the surviving sib was compound heterozygous for a 2-bp deletion (66delAG) in the first coding exon of the TBCE gene, resulting in a frameshift after residue 22 with termination at residue 48 (val23fs48Ter), and a 1113T-A transversion in exon 12 of the TBCE gene, resulting in a cys371-to-ter (C371X; 604934.0003) substitution. </p><p>Using in vitro tubulin folding assays, Tian et al. (2006) found that TBCE expressed from the 66delAG allele supported in vitro tubulin folding and enhanced TBCC (602971)- and TBCD (604649)-driven tubulin GAP activity in a manner similar to that of wildtype, whereas protein expressed from the C371X allele showed no folding greater than that of a parallel control without TBCE and had no GAP-enhancing ability. Tian et al. (2006) identified 3 out-of-frame AUG codons upstream of the 66delAG mutation and demonstrated the existence of cryptic translation initiation at each of them. Tian et al. (2006) concluded that these cryptically initiated functional polypeptides explain the survival of affected individuals homozygous for mutated alleles that apparently lack the capacity to make functional TBCE. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 HYPOPARATHYROIDISM-RETARDATION-DYSMORPHISM SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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TBCE, CYS371TER
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<br />
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SNP: rs121908384,
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ClinVar: RCV000005611
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the cys371-to-ter (C371X) mutation in the TBCE gene that was found in compound heterozygosity in a Belgian patient with hypoparathyroidism-retardation-dysmorphism syndrome (HRDS; 241410) by Parvari et al. (2002), see 604934.0002. </p>
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<strong>.0004 ENCEPHALOPATHY, PROGRESSIVE, WITH AMYOTROPHY AND OPTIC ATROPHY</strong>
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TBCE, ILE155ASN ({dbSNP rs780472451})
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SNP: rs780472451,
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gnomAD: rs780472451,
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ClinVar: RCV000412509, RCV001569082
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<p>In 5 patients from 3 unrelated families originating from the same region in Southern Italy with progressive encephalopathy with amyotrophy and optic atrophy (PEAMO; 617207), Sferra et al. (2016) identified a homozygous c.464T-A transversion (c.464T-A, NM_001079515.2) in the TBCE gene resulting in an ile155-to-asn (I155N) substitution at a highly conserved residue in the LRR domain. The mutation was noted in the text as c.464T-A, although in most of the sections of Table 1 it was referred to as c.463T-A. The mutation in 2 families was found by whole-exome sequencing and confirmed by Sanger sequencing; the mutation in a pair of affected monozygotic twins in the third family was found by mutation scan of the TBCE gene. Another patient (2518864) with the disorder was found to be compound heterozygous for the I155N mutation and a 1-bp deletion (c.1076delC; 604934.0005), resulting in a frameshift and premature termination (Leu360Ter). The mutations segregated with the disorder in all families. Both mutations were found at a low frequency in the dbSNP and ExAC databases: the frequency in ExAC was 0.000008 for I155N and 0.00002 for c.1076delC. Haplotype analysis of the families indicated a founder effect for I155N, although that variant was not found in 400 control individuals from the same geographic region near Naples. Western blot analysis of patient fibroblasts showed significantly reduced amounts of mutant TBCE protein compared to controls, with lower levels in the patient with compound heterozygous mutations. RNA analysis of patient cells showed normal levels in the patient homozygous for I155N, but decreased amounts of RNA in the compound heterozygous patient, suggesting that the 1-bp deletion resulted in nonsense-mediated mRNA decay. Patient cells showed decreased levels of polymerized alpha-tubulin and altered microtubule dynamics with decreased nucleation and markedly delayed microtubule repolymerization; microtubules were less abundant and strongly disorganized in both early and late stages of repolymerization, and there was loss of compaction in the Golgi apparatus. There was also abnormal mitotic morphology with abnormal mitotic spindles and disorganized microtubule arrangement. Sferra et al. (2016) concluded that the 155N allele is hypomorphic. </p>
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<span class="mim-font">
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<strong>.0005 ENCEPHALOPATHY, PROGRESSIVE, WITH AMYOTROPHY AND OPTIC ATROPHY</strong>
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<span class="mim-text-font">
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TBCE, 1-BP DEL, 1076C ({dbSNP rs750781063})
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SNP: rs750781063,
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gnomAD: rs750781063,
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ClinVar: RCV000412635, RCV002298580, RCV003558367
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<p>For discussion of the 1-bp deletion (c.1076delC, NM_001079515.2) in the TBCE gene, resulting in a frameshift and premature termination (Leu360Ter), that was found in compound heterozygous state in a patient with progressive encephalopathy with amyotrophy and optic atrophy (PEAMO; 617207) by Sferra et al. (2016), see 604934.0004. </p>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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Diaz, G. A., Gelb, B. D., Ali, F., Sakati, N., Sanjad, S., Meyer, B. F., Kambouris, M.
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<strong>Sanjad-Sakati and autosomal recessive Kenny-Caffey syndromes are allelic: evidence for an ancestral founder mutation and locus refinement.</strong>
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Martin, N., Jaubert, J., Gounon, P., Salido, E., Haase, G., Szatanik, M., Guenet, J.-L.
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<strong>A missense mutation in Tbce causes progressive motor neuronopathy in mice.</strong>
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[PubMed: 12389029]
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[Full Text: https://doi.org/10.1038/ng1016]
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Parvari, R., Hershkovitz, E., Grossman, N., Gorodischer, R., Loeys, B., Zecic, A., Mortier, G., Gregory, S., Sharony, R., Kambouris, M., Sakati, N., Meyer, B. F., and 10 others.
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<strong>Mutation of TBCE causes hypoparathyroidism-retardation-dysmorphism and autosomal recessive Kenny-Caffey syndrome.</strong>
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Nature Genet. 32: 448-452, 2002.
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[PubMed: 12389028]
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[Full Text: https://doi.org/10.1038/ng1012]
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Rak, K., Frenz, S., Radeloff, A., Groh, J., Jablonka, S., Martini, R., Hagen, R., Mlynski, R.
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<strong>Mutation of the TBCE gene causes disturbance of microtubules in the auditory nerve and cochlear outer hair cell degeneration accompanied by progressive hearing loss in the pmn/pmn mouse.</strong>
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Exp. Neurol. 250: 333-340, 2013.
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[PubMed: 24120439]
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[Full Text: https://doi.org/10.1016/j.expneurol.2013.10.007]
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<p class="mim-text-font">
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Ratbi, I., Lyahyai, J., Kabiri, M., Banouar, M., Zerkaoui, M., Barkat, A., Sefiani, A.
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<strong>The Bedouin mutation c.155-166del of the TBCE gene in a patient with Sanjad-Sakati syndrome of Moroccan origin.</strong>
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Ann. Saudi Med. 35: 170-172, 2015.
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[PubMed: 26336027]
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[Full Text: https://doi.org/10.5144/0256-4947.2015.170]
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<p class="mim-text-font">
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Schaefer, M. K. E., Schmalbruch, H., Buhler, E., Lopez, C., Martin, N., Guenet, J.-L., Haase, G.
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<strong>Progressive motor neuronopathy: a critical role of the tubulin chaperone TBCE in axonal tubulin routing from the Golgi apparatus.</strong>
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J. Neurosci. 27: 8779-8789, 2007.
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[PubMed: 17699660]
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[Full Text: https://doi.org/10.1523/JNEUROSCI.1599-07.2007]
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Schafer, M. K., Bellouze, S., Jacquier, A., Schaller, S., Richard, L., Mathis, S., Vallat, J.-M., Haase, G.
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<strong>Sensory neuropathy in progressive motor neuronopathy (pmn) mice is associated with defects in microtubule polymerization and axonal transport.</strong>
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Brain Path. 27: 459-471, 2017.
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[PubMed: 27488538]
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[Full Text: https://doi.org/10.1111/bpa.12422]
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Schmalbruch, H. M. D., Jensen, H., Bjearg, M., Kamienniecka, Z., Kurland, L. B. S.
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[Full Text: https://doi.org/10.1097/00005072-199105000-00002]
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<p class="mim-text-font">
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Sferra, A., Baillat, G., Rizza, T., Barresi, S., Flex, E., Tasca, G., D'Amico, A., Bellacchio, E., Ciolfi, A., Caputo, V., Cecchetti, S., Torella, A., and 14 others.
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<strong>TBCE mutations cause early-onset progressive encephalopathy with distal spinal muscular atrophy.</strong>
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Am. J. Hum. Genet. 99: 974-983, 2016.
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[PubMed: 27666369]
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Tian, G., Huang, M. C., Parvari, R., Diaz, G. A., Cowan, N. J.
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<strong>Cryptic out-of-frame translational initiation of TBCE rescues tubulin formation in compound heterozygous HRD.</strong>
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[PubMed: 16938882]
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Tian, G., Huang, Y., Rommelaere, H., Vandekerckhove, J., Ampe, C., Cowan, N. J.
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<strong>Pathway leading to correctly folded beta-tubulin.</strong>
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Cassandra L. Kniffin - updated : 11/17/2016<br>Marla J. F. O'Neill - updated : 10/4/2006<br>Cassandra L. Kniffin - updated : 4/2/2003<br>Victor A. McKusick - updated : 10/23/2002
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<p>
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Thank you in advance for your generous support, <br />
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Ada Hamosh, MD, MPH <br />
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Scientific Director, OMIM <br />
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