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<title>
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Entry
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- *131244 - ENDOTHELIN RECEPTOR, TYPE B; EDNRB
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- OMIM
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</ul>
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</div>
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</nav>
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</div>
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<div id="mimSearch" class="hidden-print">
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<div class="container">
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<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
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<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
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<input type="hidden" id="mimSearchStart" name="start" value="1" />
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<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
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<input type="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
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<div class="row">
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<div class="col-lg-8 col-md-8 col-sm-8 col-xs-8">
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<div class="form-group">
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<div class="input-group">
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<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
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<div class="input-group-btn">
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<button type="submit" id="mimEntrySearchSubmit" class="btn btn-default" style="width: 5em;"><span class="glyphicon glyphicon-search"></span></button>
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<button type="button" class="btn btn-default dropdown-toggle" data-toggle="dropdown"> Options <span class="caret"></span></button>
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<ul class="dropdown-menu dropdown-menu-right">
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<li class="dropdown-header">
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Advanced Search
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/entry"> OMIM </a>
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/geneMap"> Gene Map </a>
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<li role="separator" class="divider"></li>
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<li>
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<a href="/history"> Search History </a>
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</ul>
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</div>
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</div>
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<div class="autocomplete" id="mimEntrySearchAutocomplete"></div>
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<div class="col-lg-4 col-md-4 col-sm-4 col-xs-4">
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</form>
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<p />
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</div>
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<!-- <div id="mimSearch"> -->
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-2 hidden-sm hidden-xs">
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*131244</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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</li>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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</li>
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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#biochemicalFeatures">Biochemical Features</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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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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</li>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
|
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<a href="/allelicVariants/131244">Table View</a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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</li>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
|
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
|
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<h4 class="panel-title">
|
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
|
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<div style="display: table-row">
|
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
|
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<div style="display: table-cell;">External Links</div>
|
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</div>
|
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</a>
|
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</h4>
|
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</div>
|
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
|
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<span class="panel-title">
|
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<span class="small">
|
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
|
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</a>
|
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</span>
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</span>
|
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</div>
|
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
|
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<div class="panel-body small mim-panel-body">
|
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|
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000136160;t=ENST00000646607" 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=1910" 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=131244" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
|
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<span class="panel-title">
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<span class="small">
|
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
|
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</a>
|
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000136160;t=ENST00000646607" 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_000115,NM_001122659,NM_001201397,NM_003991" 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_001122659" 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=131244" 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=08834&isoform_id=08834_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/EDNRB" 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/119622,181959,182276,219652,233234,298322,913203,2285956,4261877,4503467,4557547,4580924,15680235,20429126,20429128,20429130,20429132,30526095,42718168,62087976,119600979,119600980,119600981,119600982,119600983,119600984,158254834,169808392,319655697" 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/P24530" 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=1910" 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=ENSG00000136160;t=ENST00000646607" 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=EDNRB" 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=EDNRB" 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+1910" 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/EDNRB" 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:1910" 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/1910" 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=chr13&hgg_gene=ENST00000646607.2&hgg_start=77895487&hgg_end=77975527&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:3180" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:3180" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/ednrb" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=131244[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=131244[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/EDNRB/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000136160" 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=EDNRB" 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=EDNRB" 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=EDNRB" 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="http://grenada.lumc.nl/LOVD2/WS/home.php?select_db=EDNRB" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=EDNRB&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/PA27618" 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:3180" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:102720" 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/EDNRB#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:102720" 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/1910/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://omia.org/results?search_type=advanced&omia_id=000629,001765,002701,002808" class="mim-tip-hint" title="OMIA" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OMIA', 'domain': 'omia.angis.org.au'})">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=1910" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-081105-182" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:1910" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=EDNRB&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> 715952000<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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131244
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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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ENDOTHELIN RECEPTOR, TYPE B; EDNRB
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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">
|
|
ENDOTHELIN RECEPTOR, NONSELECTIVE TYPE; ETB<br />
|
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ETRB; ETBR
|
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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=EDNRB" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">EDNRB</a></em></strong>
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</span>
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</p>
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
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Cytogenetic location: <a href="/geneMap/13/236?start=-3&limit=10&highlight=236">13q22.3</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr13:77895487-77975527&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'})">13:77,895,487-77,975,527</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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13q22.3
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?ABCD syndrome
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{Hirschsprung disease, susceptibility to, 2}
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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Waardenburg syndrome, type 4A
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<a href="/entry/277580"> 277580 </a>
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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PheneGene Graphics <span class="caret"></span>
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</button>
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<ul class="dropdown-menu" style="width: 17em;">
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<li><a href="/graph/linear/131244" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/131244" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<h4>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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<a id="cloning" class="mim-anchor"></a>
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<h4 href="#mimCloningFold" id="mimCloningToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<p>Endothelins belong to a family of potent vasoactive peptides consisting of 3 isopeptides, ET1 (EDN1; <a href="/entry/131240">131240</a>), ET2 (EDN2; <a href="/entry/131241">131241</a>), and ET3 (EDN3; <a href="/entry/131242">131242</a>). A diverse set of pharmacologic activities with different potencies are exerted by endothelin family peptides, suggesting the existence of ET receptor subtypes. <a href="#39" class="mim-tip-reference" title="Takayanagi, R., Ohnaka, K., Takasaki, C., Ohashi, M., Nawata, H. <strong>Multiple subtypes of endothelin receptors in porcine tissues: characterization by ligand binding, affinity labeling and regional distribution.</strong> Regul. Pept. 32: 23-37, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1848367/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1848367</a>] [<a href="https://doi.org/10.1016/0167-0115(91)90004-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1848367">Takayanagi et al. (1991)</a> described 2 distinct subclasses of ET receptors, namely, ET1-specific and ET-nonselective. <a href="#41" class="mim-tip-reference" title="Vane, J. R. <strong>Endothelins come home to roost.</strong> Nature 348: 673, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2175394/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2175394</a>] [<a href="https://doi.org/10.1038/348673a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2175394">Vane (1990)</a> recommended that the ET1-specific type be called ETA and the nonselective type ETB. <a href="#27" class="mim-tip-reference" title="Nakamuta, M., Takayanagi, R., Sakai, Y., Sakamoto, S., Hagiwara, H., Mizuno, T., Saito, Y., Hirose, S., Yamamoto, M., Nawata, H. <strong>Cloning and sequence analysis of a cDNA encoding human non-selective type of endothelin receptor.</strong> Biochem. Biophys. Res. Commun. 177: 34-39, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1710450/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1710450</a>] [<a href="https://doi.org/10.1016/0006-291x(91)91944-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1710450">Nakamuta et al. (1991)</a> isolated a cDNA encoding human ETB receptor from a cDNA library constructed from human liver. Hepatocytes have a considerable number of ET receptors linked to biologic actions such as glycogenolysis. The cDNA had an open reading frame encoding a protein of 442 amino acid residues with a relative mass of 49,643. The deduced amino acid sequence of the human ETB receptor was 88% and 64% identical to those of rat lung ETB receptor and bovine lung ET1-specific receptor, respectively. <a href="#28" class="mim-tip-reference" title="Ogawa, Y., Nakao, K., Arai, H., Nakagawa, O., Hosoda, K., Suga, S., Nakanishi, S., Imura, H. <strong>Molecular cloning of a non-isopeptide-selective human endothelin receptor.</strong> Biochem. Biophys. Res. Commun. 178: 248-255, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1648908/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1648908</a>] [<a href="https://doi.org/10.1016/0006-291x(91)91806-n" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1648908">Ogawa et al. (1991)</a> likewise isolated a nonisopeptide-selective human endothelin receptor from a human placenta cDNA library. The predicted protein had 442 amino acids with a transmembrane topology similar to that of other G protein-coupled receptors. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1710450+2175394+1848367+1648908" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Elshourbagy, N. A., Adamou, J. E., Gagnon. A. W., Wu, H.-L., Pullen, M., Nambi, P. <strong>Molecular characterization of a novel human endothelin receptor splice variant.</strong> J. Biol. Chem. 271: 25300-25307, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8810293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8810293</a>] [<a href="https://doi.org/10.1074/jbc.271.41.25300" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8810293">Elshourbagy et al. (1996)</a> isolated a novel splice variant of the endothelin-B receptor which they termed ETB-SVR. The sequence of the ETB-SVR receptor is identical to ETRB except for the intracellular C-terminal domain. The ETB-SVR receptor is expressed as a 2.7-kb mRNA in the lung, placenta, kidney, and skeletal muscle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8810293" 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="#12" class="mim-tip-reference" title="Elshourbagy, N. A., Adamou, J. E., Gagnon. A. W., Wu, H.-L., Pullen, M., Nambi, P. <strong>Molecular characterization of a novel human endothelin receptor splice variant.</strong> J. Biol. Chem. 271: 25300-25307, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8810293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8810293</a>] [<a href="https://doi.org/10.1074/jbc.271.41.25300" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8810293">Elshourbagy et al. (1996)</a> transfected COS cells with ETB-SVR or ETRB and found that both receptors bind to ET1. However, while ETRB-transfected cells responded to ET1 with increases in inositol phosphate accumulation and intracellular acidification, ETB-SVR-transfected cells did not exhibit either of these responses to ET1. These data suggested to <a href="#12" class="mim-tip-reference" title="Elshourbagy, N. A., Adamou, J. E., Gagnon. A. W., Wu, H.-L., Pullen, M., Nambi, P. <strong>Molecular characterization of a novel human endothelin receptor splice variant.</strong> J. Biol. Chem. 271: 25300-25307, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8810293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8810293</a>] [<a href="https://doi.org/10.1074/jbc.271.41.25300" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8810293">Elshourbagy et al. (1996)</a> that ETB-SVR and ETRB are functionally distinct, and that the difference in the C-terminal amino acid sequences determines functional coupling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8810293" 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>To investigate the influence of pregnancy-specific hormonal environment on expression of ET1 and ET1 receptor (EDNRA; <a href="/entry/131243">131243</a>), <a href="#5" class="mim-tip-reference" title="Bourgeois, C., Robert, B., Rebourcet, R., Mondon, F., Mignot, T.-M., Duc-Goiran, P., Ferre, F. <strong>Endothelin-1 and ET(A) receptor expression in vascular smooth muscle cells from human placenta: a new ET(A) receptor messenger ribonucleic acid is generated by alternative splicing of exon 3.</strong> J. Clin. Endocr. Metab. 82: 3116-3123, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9284755/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9284755</a>] [<a href="https://doi.org/10.1210/jcem.82.9.4209" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9284755">Bourgeois et al. (1997)</a> investigated whether the muscular layer of stem villi vessels could be a site of the ET1 expression. The authors found that whereas both EDNRA and EDNRB are present in stem villi vessels, placental vascular smooth muscle cells exclusively express the EDNRA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9284755" 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="#24" class="mim-tip-reference" title="Maggi, M., Barni, T., Fantoni, G., Mancina, R., Pupilli, C., Luconi, M., Crescioli, C., Serio, M., Vannelli, G. B. <strong>Expression and biological effects of endothelin-1 in human gonadotropin-releasing hormone-secreting neurons.</strong> J. Clin. Endocr. Metab. 85: 1658-1665, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10770212/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10770212</a>] [<a href="https://doi.org/10.1210/jcem.85.4.6565" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10770212">Maggi et al. (2000)</a> demonstrated that in FNC-B4 cells, which are derived from a human fetal olfactory epithelium, both sex steroids and odorants regulate GnRH secretion. They found biologic activity of EDN1 in this GnRH-secreting neuronal cell. In situ hybridization and immunohistochemistry revealed gene and protein expression of EDN1 and its converting enzyme (ECE1; <a href="/entry/600423">600423</a>) in both fetal olfactory mucosa and FNC-B4 cells. Experiments with radiolabeled EDN1 and EDN3 strongly indicated the presence of 2 classes of binding sites, corresponding to the ETA (16,500 sites/cell) and the ETB receptors (8,700 sites/cell). Functional studies using selective analogs indicated that these 2 classes of receptors subserve distinct functions in human GnRH-secreting cells. The ETA receptor subtype mediated an increase in intracellular calcium and GnRH secretion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10770212" 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>Endothelin-1 inhibits active Na-K transport by as much as 50% in the renal tubule and other tissues (<a href="#46" class="mim-tip-reference" title="Zeidel, M. L., Brady, H. R., Kone, B. C., Gullans, S. R., Brenner, B. M. <strong>Endothelin, a peptide inhibitor of Na(+)-K(+)-ATPase in intact renal tubular epithelial cells.</strong> Am. J. Physiol. 257: C1101-C1107, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2558568/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2558568</a>] [<a href="https://doi.org/10.1152/ajpcell.1989.257.6.C1101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2558568">Zeidel et al., 1989</a>). <a href="#29" class="mim-tip-reference" title="Okafor, M. C., Delamere, N. A. <strong>The inhibitory influence of endothelin on active sodium-potassium transport in porcine lens.</strong> Invest. Ophthal. Vis. Sci. 42: 1018-1023, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11274080/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11274080</a>]" pmid="11274080">Okafor and Delamere (2001)</a> noted that the presence of low levels of ET1 in aqueous humor combined with the potential for release of ET1 from ciliary processes suggested that the crystalline lens could be exposed to ET1 in vivo. They studied the influence of ET1 on active Na-K transport in the porcine lens. Their results suggested that ET1 inhibited active lens Na-K transport by activating EDNRA and EDNRB. Activation of the ET receptors also caused an increase in cytoplasmic calcium concentration in cultured lens epithelial cells. Both responses to ET1 appear to have a tyrosine kinase step. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11274080+2558568" 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>The 5-prime region of EDNRB is a complex CpG island giving rise to 4 individual transcripts initiating within the island. <a href="#30" class="mim-tip-reference" title="Pao, M. M., Tsutsumi, M., Liang, G., Uzvolgyi, E., Gonzales, F. A., Jones, P. A. <strong>The endothelin receptor B (EDNRB) promoter displays heterogeneous, site specific methylation patterns in normal and tumor cells.</strong> Hum. Molec. Genet. 10: 903-910, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11309363/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11309363</a>] [<a href="https://doi.org/10.1093/hmg/10.9.903" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11309363">Pao et al. (2001)</a> analyzed the relationship between methylation and EDNRB expression in human tissues. The CpG island was unmethylated in normal prostate and bladder tissue, whereas it was methylated in colonic epithelium; DNA from tumors derived from these tissues was frequently hypermethylated. Analysis of 11 individual CpG sites in the CpG island showed that specific sites with high methylation levels in several tumors and cancer cell lines were also methylated in normal tissues, suggesting that these sites might serve as foci for further de novo methylation. A low methylation level in a small region within the 5-prime region correlated with expression of the 5-prime-most transcript, whereas almost complete methylation 200 to 1000 bp downstream of the transcriptional start site did not block expression of this transcript. Treatment with 5-aza-2-prime-deoxycytidine induced transcriptional activation of all 4 EDNRB transcripts. The authors concluded that there is differential, tissue-dependent methylation at the EDNRB 5-prime region, and that hypermethylation immediately 3-prime to the transcriptional start site does not prevent initiation. They further proposed a spreading mechanism for de novo methylation, starting from particular methylation hotspots. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11309363" 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>Endothelin-1 is synthesized by keratinocytes in normal skin and is locally released after cutaneous injury. It is able to trigger pain through its actions on endothelin-A receptors of local nociceptors, but coincidentally produces analgesia through endothelin-B receptors. <a href="#20" class="mim-tip-reference" title="Khodorova, A., Navarro, B., Jouaville, L. S., Murphy, J.-E., Rice, F. I., Mazurkiewicz, J. E., Long-Woodward, D., Stoffel, M., Strichartz, G. R., Yukhananov, R., Davar, G. <strong>Endothelin-B receptor activation triggers an endogenous analgesic cascade at sites of peripheral injury.</strong> Nature Med. 9: 1055-1061, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12847519/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12847519</a>] [<a href="https://doi.org/10.1038/nm885" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12847519">Khodorova et al. (2003)</a> mapped an endogenous analgesic circuit, in which endothelin-B receptor activation induces the release of beta-endorphin from keratinocytes and the activation of G protein-coupled inwardly rectifying potassium channels (GIRKs, also called Kir-3) linked to opioid receptors on nociceptors. These results indicated the existence of an intrinsic feedback mechanism to control peripheral pain in skin, and established keratinocytes as an endothelin-B receptor-operated opioid pool. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12847519" 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 gene expression profiling, <a href="#19" class="mim-tip-reference" title="Iwashita, T., Kruger, G. M., Pardal, R., Kiel, M. J., Morrison, S. J. <strong>Hirschsprung disease is linked to defects in neural crest stem cell function.</strong> Science 301: 972-976, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12920301/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12920301</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12920301[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/10.1126/science.1085649" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12920301">Iwashita et al. (2003)</a> determined that genes associated with Hirschsprung disease were highly upregulated in rat gut neural crest stem cells relative to whole-fetus RNA. The genes with highest expression were GDNF (<a href="/entry/600837">600837</a>), SOX10 (<a href="/entry/602229">602229</a>), GFRA1 (<a href="/entry/601496">601496</a>), and EDNRB. The highest expression was seen in RET (<a href="/entry/164761">164761</a>), which was found to be necessary for neural crest stem cell migration in the gut. GDNF promoted the migration of neural crest stem cells in culture but did not affect their survival or proliferation. The observations made by <a href="#19" class="mim-tip-reference" title="Iwashita, T., Kruger, G. M., Pardal, R., Kiel, M. J., Morrison, S. J. <strong>Hirschsprung disease is linked to defects in neural crest stem cell function.</strong> Science 301: 972-976, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12920301/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12920301</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12920301[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/10.1126/science.1085649" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12920301">Iwashita et al. (2003)</a> were confirmed by quantitative RT-PCR, flow cytometry, and functional analysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12920301" 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="#43" class="mim-tip-reference" title="Wang, L., Fortune, B., Cull, G., Dong, J., Cioffi, G. A. <strong>Endothelin B receptor in human glaucoma and experimentally induced optic nerve damage.</strong> Arch. Ophthal. 124: 717-724, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16682595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16682595</a>] [<a href="https://doi.org/10.1001/archopht.124.5.717" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16682595">Wang et al. (2006)</a> assessed EDNRB expression in human glaucomatous optic nerves and the spatial relationship between EDNRB and astrocytes. The frequency of positive EDNRB immunoreactivity was significantly higher in human glaucomatous optic nerves as compared with age-matched controls (9/16 vs 1/10). EDNRB colocalized with astrocytic processes and was quantitatively higher in the glaucomatous eyes. <a href="#43" class="mim-tip-reference" title="Wang, L., Fortune, B., Cull, G., Dong, J., Cioffi, G. A. <strong>Endothelin B receptor in human glaucoma and experimentally induced optic nerve damage.</strong> Arch. Ophthal. 124: 717-724, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16682595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16682595</a>] [<a href="https://doi.org/10.1001/archopht.124.5.717" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16682595">Wang et al. (2006)</a> concluded that increased EDNRB immunoreactivity in diseased optic nerves and its association with astrocytes suggested that the glia-endothelin system might be involved in the pathologic mechanisms of neuronal degeneration. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16682595" 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 transcription profiling of microdissected tumor endothelial cells from human ovarian cancers, <a href="#6" class="mim-tip-reference" title="Buckanovich, R. J., Facciabene, A., Kim, S., Benencia, F., Sasaroli, D., Balint, K., Katsaros, D., O'Brien-Jenkins, A., Gimotty, P. A., Coukos, G. <strong>Endothelin B receptor mediates the endothelial barrier to T cell homing to tumors and disables immune therapy.</strong> Nature Med. 14: 28-36, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18157142/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18157142</a>] [<a href="https://doi.org/10.1038/nm1699" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18157142">Buckanovich et al. (2008)</a> found that overexpression of ETBR was associated with absence of tumor-infiltrating lymphocytes and short patient survival time. An ETBR inhibitor increased adhesion of T cells to human endothelium in vitro, and this effect was countered by ICAM1 (<a href="/entry/147840">147840</a>) blockade or treatment with nitric oxide donors. Mice treated with the ETBR inhibitor displayed increased Icam1-dependent T-cell homing to tumors. ETBR inhibitor treatment enabled a tumor response in otherwise ineffective immunotherapy without altering the systemic antitumor immune response. <a href="#6" class="mim-tip-reference" title="Buckanovich, R. J., Facciabene, A., Kim, S., Benencia, F., Sasaroli, D., Balint, K., Katsaros, D., O'Brien-Jenkins, A., Gimotty, P. A., Coukos, G. <strong>Endothelin B receptor mediates the endothelial barrier to T cell homing to tumors and disables immune therapy.</strong> Nature Med. 14: 28-36, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18157142/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18157142</a>] [<a href="https://doi.org/10.1038/nm1699" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18157142">Buckanovich et al. (2008)</a> proposed that mixed ETAR-ETBR blockade could simultaneously target tumor cells through ETAR and enhance antitumor immune mechanisms through vascular ETBR. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18157142" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#2" class="mim-tip-reference" title="Arai, H., Nakao, K., Takaya, K., Hosoda, K., Ogawa, Y., Nakanishi, S., Imura, H. <strong>The human endothelin-B receptor gene: structural organization and chromosomal assignment.</strong> J. Biol. Chem. 268: 3463-3470, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8429023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8429023</a>]" pmid="8429023">Arai et al. (1993)</a> demonstrated that the human genome contains a single copy of the ETRB gene, which spans 24 kb and comprises 7 exons and 6 introns. Every intron occurs near the border of the putative transmembrane domain in the coding region. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8429023" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using human/rodent somatic hybrid cell lines, <a href="#2" class="mim-tip-reference" title="Arai, H., Nakao, K., Takaya, K., Hosoda, K., Ogawa, Y., Nakanishi, S., Imura, H. <strong>The human endothelin-B receptor gene: structural organization and chromosomal assignment.</strong> J. Biol. Chem. 268: 3463-3470, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8429023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8429023</a>]" pmid="8429023">Arai et al. (1993)</a> assigned the ETRB gene to human chromosome 13. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8429023" 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="#34" class="mim-tip-reference" title="Shihoya, W., Nishizawa, T., Okuta, A., Tani, K., Dohmae, N., Fujiyoshi, Y., Nureki, O., Doi, T. <strong>Activation mechanism of endothelin ET(B) receptor by endothelin-1.</strong> Nature 537: 363-368, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27595334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27595334</a>] [<a href="https://doi.org/10.1038/nature19319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27595334">Shihoya et al. (2016)</a>, reported the crystal structures of human endothelin type B receptor in the ligand-free form and in complex with the endogenous agonist endothelin-1 (<a href="/entry/131240">131240</a>). The structures and mutation analysis revealed the mechanism for the isopeptide selectivity between endothelin-1 and -3. Transmembrane helices 1, 2, 6, and 7 move and envelop the entire endothelin peptide in a virtually irreversible manner. The agonist-induced conformational changes are propagated to the receptor core and the cytoplasmic G protein-coupling interface, and probably induce conformational flexibility in TM6. A comparison with the M2 muscarinic receptor (CHRM2; <a href="/entry/118493">118493</a>) suggested a shared mechanism for signal transduction in class A G protein-coupled receptors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27595334" 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="#31" class="mim-tip-reference" title="Puffenberger, E. G., Hosoda, K., Washington, S. S., Nakao, K., deWit, D., Yanagisawa, M., Chakravarti, A. <strong>A missense mutation of the endothelin-B receptor gene in multigenic Hirschsprung's disease.</strong> Cell 79: 1257-1266, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8001158/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8001158</a>] [<a href="https://doi.org/10.1016/0092-8674(94)90016-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8001158">Puffenberger et al. (1994)</a> presented evidence that Hirschsprung disease (HSCR2; <a href="/entry/600155">600155</a>), an apparently multigenic disorder, can result in some cases from mutation in the endothelin-B receptor gene. EDNRB was a candidate gene because it mapped to the same region of chromosome 13 as did HSCR2. A trp276-to-cys mutation (W276C; <a href="#0001">131244.0001</a>) was dosage sensitive in that homozygotes and heterozygotes had a 74% and a 21% risk, respectively, of developing HSCR. For all clinical forms of HSCR, there is a greater incidence of megacolon in males than in females and the same was true for the specific EDNRB mutation. However, among the Mennonites, at least 5 megacolon patients did not seem to carry the W276C EDNRB mutation present in most of the affected members, which suggested the existence of as yet undiscovered HSCR susceptibility genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8001158" 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="#21" class="mim-tip-reference" title="Kusafuka, T., Wang, Y., Puri, P. <strong>Novel mutations of the endothelin-B receptor gene in isolated patients with Hirschsprung's disease.</strong> Hum. Molec. Genet. 5: 347-349, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8852658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8852658</a>] [<a href="https://doi.org/10.1093/hmg/5.3.347" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8852658">Kusafuka et al. (1996)</a> analyzed 7 exons for mutations in the EDNRB gene in 41 isolated patients with HSCR. Two novel mutations were detected (<a href="#0003">131244.0003</a> and <a href="#0004">131244.0004</a>). Both patients with the novel mutations were heterozygotes. No information was provided on the families of these 2 cases, but the presumption was that they represented new mutations. <a href="#1" class="mim-tip-reference" title="Amiel, J., Attie, T., Jan, D., Pelet, A., Edery, P., Bidaud, C., Lacombe, D., Tam, P., Simeoni, J., Flori, E., Nihoul-Fekete, C., Munnich, A., Lyonnet, S. <strong>Heterozygous endothelin receptor B (EDNRB) mutations in isolated Hirschsprung disease.</strong> Hum. Molec. Genet. 5: 355-357, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8852660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8852660</a>] [<a href="https://doi.org/10.1093/hmg/5.3.355" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8852660">Amiel et al. (1996)</a> reported 3 missense mutations in the EDNRB gene in heterozygous state in sporadic cases of HSCR. <a href="#11" class="mim-tip-reference" title="Chakravarti, A. <strong>Endothelin receptor-mediated signaling in Hirschsprung disease.</strong> Hum. Molec. Genet. 5: 303-307, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8852653/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8852653</a>]" pmid="8852653">Chakravarti (1996)</a> tabulated 12 mutations in the EDNRB gene identified in cases of Hirschsprung disease up to that time. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8852660+8852653+8852658" 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>Among 31 isolated cases of Hirschsprung disease in non-inbred populations in Japan, <a href="#40" class="mim-tip-reference" title="Tanaka, H., Moroi, K., Iwai, J., Takahashi, H., Ohnuma, N., Hori, S., Takimoto, M., Nishiyama, M., Masaki, T., Yanagisawa, M., Sekiya, S., Kimura, S. <strong>Novel mutations of the endothelin B receptor gene in patients with Hirschsprung's disease and their characterization.</strong> J. Biol. Chem. 273: 11378-11383, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9556633/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9556633</a>] [<a href="https://doi.org/10.1074/jbc.273.18.11378" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9556633">Tanaka et al. (1998)</a> identified 3 new mutations in the EDNRB gene: 2 transversions, A to T and C to A at nucleotides 311 (N104I) and 1170 (S390R), respectively, and a T-to-C transition at nucleotide 325 (C109R). In vitro functional expression studies in Chinese hamster ovary cells revealed that N104I receptors showed almost the same binding affinities and functional properties as the wildtype and might represent a polymorphism. On the other hand, although S390R did not change the binding affinities, it caused decreases in the ligand-induced increment of intracellular calcium and in the inhibition of adenylyl cyclase activity, showing the impairment of the intracellular signaling. C109R receptors were proved to be localized near the nuclei as an unusual 44-kD protein with an extremely low affinity to endothelin-1 and not to be translocated into the plasma membrane. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9556633" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Chakravarti, A. <strong>Endothelin receptor-mediated signaling in Hirschsprung disease.</strong> Hum. Molec. Genet. 5: 303-307, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8852653/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8852653</a>]" pmid="8852653">Chakravarti (1996)</a> estimated that RET (<a href="/entry/164761">164761</a>) mutations account for approximately 50% of HSCR cases and EDNRB mutations account for approximately 5%. Short-segment HSCR occurs in about 25% of RET-caused cases and in more than 95% of EDNRB-related cases. Whereas homozygosity for the EDNRB gene can cause deafness and pigmentary anomalies in addition to HSCR (e.g., <a href="#0002">131244.0002</a>), the homozygous phenotype for RET has not been observed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8852653" 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="Carrasquillo, M. M., McCallion, A. S., Puffenberger, E. G., Kashuk, C. S., Nouri, N., Chakravarti, A. <strong>Genome-wide association study and mouse model identify interaction between RET and EDNRB pathways in Hirschsprung disease.</strong> Nature Genet. 32: 237-244, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12355085/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12355085</a>] [<a href="https://doi.org/10.1038/ng998" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12355085">Carrasquillo et al. (2002)</a> noted that although 8 genes with mutations that can be associated with Hirschsprung disease had been identified, mutations at individual loci are neither necessary nor sufficient to cause clinical disease. They conducted a genomewide association study in 43 Mennonite family trios (parents and affected child) using 2,083 microsatellites and SNPs and a new multipoint linkage disequilibrium method that searched for association arising from common ancestry. They identified susceptibility loci at 10q11, 13q22, and 16q23 (HSCR8; <a href="/entry/608462">608462</a>); they showed that the gene at 13q22 is EDNRB and the gene at 10q11 is RET. Statistically significant joint transmission of RET and EDNRB alleles in affected individuals and noncomplementation of aganglionosis in mouse intercrosses between Ret-null and the Ednrb hypomorphic piebald allele were suggestive of epistasis between EDNRB and RET. The findings suggested that genetic interaction between mutations in RET and EDNRB is an underlying mechanism for this complex disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12355085" 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="#32" class="mim-tip-reference" title="Sanchez-Mejias, A., Fernandez, R. M., Lopez-Alonso, M., Antinolo, G., Borrego, S. <strong>New roles of EDNRB and EDN3 in the pathogenesis of Hirschsprung disease.</strong> Genet. Med. 12: 39-43, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20009762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20009762</a>] [<a href="https://doi.org/10.1097/GIM.0b013e3181c371b0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20009762">Sanchez-Mejias et al. (2010)</a> screened the EDN3 (<a href="/entry/131242">131242</a>) and EDNRB genes in 196 patients with Hirschsprung disease from Spain using high performance liquid chromatography. They found 25 sequence variants in the EDNRB gene; 17 of these were novel. <a href="#32" class="mim-tip-reference" title="Sanchez-Mejias, A., Fernandez, R. M., Lopez-Alonso, M., Antinolo, G., Borrego, S. <strong>New roles of EDNRB and EDN3 in the pathogenesis of Hirschsprung disease.</strong> Genet. Med. 12: 39-43, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20009762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20009762</a>] [<a href="https://doi.org/10.1097/GIM.0b013e3181c371b0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20009762">Sanchez-Mejias et al. (2010)</a> screened an additional exon in the 5-prime direction from exon 1 of EDNRB, never previously analyzed in the context of HSCR. Inclusion of this additional exon results in a transcript variant, termed EDNRB-delta-3, with 89 additional amino acids at the N-terminal region of the protein relative to conventional EDNRB. <a href="#32" class="mim-tip-reference" title="Sanchez-Mejias, A., Fernandez, R. M., Lopez-Alonso, M., Antinolo, G., Borrego, S. <strong>New roles of EDNRB and EDN3 in the pathogenesis of Hirschsprung disease.</strong> Genet. Med. 12: 39-43, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20009762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20009762</a>] [<a href="https://doi.org/10.1097/GIM.0b013e3181c371b0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20009762">Sanchez-Mejias et al. (2010)</a> detected 3 sequence variants at the 5-prime untranslated region of this additional exon. The most striking finding was the detection of a coding mutation, lys15-to-ter (<a href="#0009">131244.0009</a>), in a sporadic Hirschsprung disease patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20009762" 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>Waardenburg Syndrome Type 4A</em></strong></p><p>
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<a href="#31" class="mim-tip-reference" title="Puffenberger, E. G., Hosoda, K., Washington, S. S., Nakao, K., deWit, D., Yanagisawa, M., Chakravarti, A. <strong>A missense mutation of the endothelin-B receptor gene in multigenic Hirschsprung's disease.</strong> Cell 79: 1257-1266, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8001158/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8001158</a>] [<a href="https://doi.org/10.1016/0092-8674(94)90016-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8001158">Puffenberger et al. (1994)</a> found that some Mennonites had HSCR associated with nonenteric phenotypes, including bicolored irides (6.3%), hypopigmentation (2.5%), sensorineural hearing loss (5.1%), and white forelock (7.6%), reminiscent of the Shah-Waardenburg syndrome (WS4A; <a href="/entry/277580">277580</a>). <a href="#31" class="mim-tip-reference" title="Puffenberger, E. G., Hosoda, K., Washington, S. S., Nakao, K., deWit, D., Yanagisawa, M., Chakravarti, A. <strong>A missense mutation of the endothelin-B receptor gene in multigenic Hirschsprung's disease.</strong> Cell 79: 1257-1266, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8001158/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8001158</a>] [<a href="https://doi.org/10.1016/0092-8674(94)90016-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8001158">Puffenberger et al. (1994)</a> suggested that these nonenteric features represented pleiotropic effects of the W276C mutation. They pointed out that the mouse piebald mutation 's' demonstrates white coat spotting as the only phenotypic trait, whereas the piebald-lethal mouse 's(l)' has megacolon in addition to white coat color (<a href="#22" class="mim-tip-reference" title="Lane, P. W. <strong>Association of megacolon with two recessive spotting genes in the mouse.</strong> J. Hered. 57: 29-31, 1966.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5917257/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5917257</a>] [<a href="https://doi.org/10.1093/oxfordjournals.jhered.a107457" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5917257">Lane, 1966</a>). <a href="#18" class="mim-tip-reference" title="Hosoda, K., Hammer, R. E., Richardson, J. A., Baynash, A. G., Cheung, J. C., Giaid, A., Yanagisawa, M. <strong>Targeted and natural (piebald-lethal) mutations of endothelin-B receptor gene produce megacolon associated with spotted coat color in mice.</strong> Cell 79: 1267-1276, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8001159/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8001159</a>] [<a href="https://doi.org/10.1016/0092-8674(94)90017-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8001159">Hosoda et al. (1994)</a> found that targeted and natural ('piebald-lethal') mutations of the Ednrb mouse result in megacolon associated with spotted coat color. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8001159+5917257+8001158" 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>ABCD Syndrome</em></strong></p><p>
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In a child with ABCD syndrome (<a href="/entry/600501">600501</a>) reported by <a href="#16" class="mim-tip-reference" title="Gross, A., Kunze, J., Maier, R. F., Stoltenburg-Didinger, G., Grimmer, I., Obladen, M. <strong>Autosomal-recessive neural crest syndrome with albinism, black lock, cell migration disorder of the neurocytes of the gut, and deafness: ABCD syndrome.</strong> Am. J. Med. Genet. 56: 322-326, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7778600/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7778600</a>] [<a href="https://doi.org/10.1002/ajmg.1320560322" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7778600">Gross et al. (1995)</a>, <a href="#42" class="mim-tip-reference" title="Verheij, J. B. G. M., Kunze, J., Osinga, J., van Essen, A. J., Hofstra, R. M. W. <strong>ABCD syndrome is caused by a homozygous mutation in the EDNRB gene.</strong> Am. J. Med. Genet. 108: 223-225, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11891690/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11891690</a>] [<a href="https://doi.org/10.1002/ajmg.10172" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11891690">Verheij et al. (2002)</a> identified a homozygous nonsense mutation in the EDNRB gene (<a href="#0008">131244.0008</a>). <a href="#42" class="mim-tip-reference" title="Verheij, J. B. G. M., Kunze, J., Osinga, J., van Essen, A. J., Hofstra, R. M. W. <strong>ABCD syndrome is caused by a homozygous mutation in the EDNRB gene.</strong> Am. J. Med. Genet. 108: 223-225, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11891690/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11891690</a>] [<a href="https://doi.org/10.1002/ajmg.10172" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11891690">Verheij et al. (2002)</a> concluded that the ABCD syndrome is not a separate entity, but rather an expression of Shah-Waardenburg syndrome (WS4). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11891690+7778600" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The autosomal recessive 'spotting lethal' (sl) mutation in the rat is characterized by absence of intramural ganglion cells in the entire colon and distal small bowel, thus resembling human Hirschsprung disease. <a href="#10" class="mim-tip-reference" title="Ceccherini, I., Zhang, A. L., Matera, I., Yang, G., Devoto, M., Romeo, G., Cass, D. T. <strong>Interstitial deletion of the endothelin-B receptor gene in the spotting lethal (sl) rat.</strong> Hum. Molec. Genet. 4: 2089-2096, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8589685/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8589685</a>] [<a href="https://doi.org/10.1093/hmg/4.11.2089" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8589685">Ceccherini et al. (1995)</a> excluded linkage of sl with 2 candidate genes, RET protooncogene (RET; <a href="/entry/164761">164761</a>) and endothelin-3; however, a highly significant lod score (Z = 47.05 at theta = 0.0) was found between EDNRB and the sl phenotype. The exon-intron structure of the rat gene was reconstructed and each exon of the sl rat was screened for mutations. A 301-bp interstitial deletion, encompassing the distal half of the first coding exon (exon 2) and the proximal part of the adjacent intron, was demonstrated. This deletion resulted in 2 transcriptional products, 270 and 238 bp shorter than wildtype cDNA. <a href="#13" class="mim-tip-reference" title="Gariepy, C. E., Cass, D. T., Yanagisawa, M. <strong>Null mutation of endothelin receptor type B gene in spotting lethal rats causes aganglionic megacolon and white coat color.</strong> Proc. Nat. Acad. Sci. 93: 867-872, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8570650/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8570650</a>] [<a href="https://doi.org/10.1073/pnas.93.2.867" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8570650">Gariepy et al. (1996)</a> showed that the deletion perfectly cosegregates with the sl phenotype. The deletion leads to production of an aberrantly spliced EDNRB mRNA that lacks the coding sequence for the first and second putative transmembrane domains of the G protein-coupled receptor. Radioligand binding assays revealed undetectable levels of functional EDNRB in tissues from homozygous sl/sl rats. Thus, the authors concluded that EDNRB plays an essential role in the normal development of 2 neural crest-derived cell lineages, epidermal melanocytes and enteric neurons, in 3 mammalian species--humans, mice, and rats. They stated that rats lacking EDNRB may prove valuable in studies of adult physiology in health and diseases, if the sl rat can be rescued from the lethal megacolon phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8589685+8570650" 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="#15" class="mim-tip-reference" title="Gariepy, C. E., Williams, S. C., Richardson, J. A., Hammer, R. E., Yanagisawa, M. <strong>Transgenic expression of the endothelin-B receptor prevents congenital intestinal aganglionosis in a rat model of Hirschsprung disease.</strong> J. Clin. Invest. 102: 1092-1101, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9739043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9739043</a>] [<a href="https://doi.org/10.1172/JCI3702" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9739043">Gariepy et al. (1998)</a> demonstrated that during normal rat development the EDNRB mRNA expression pattern is consistent with expression by enteric nervous system (ENS) precursors throughout gut colonization. They used the human dopamine-beta-hydroxylase (DBH; <a href="/entry/223360">223360</a>) promoter to direct transgenic expression of EDNRB to colonizing ENS precursors in the sl/sl rat. The DBH-EDNRB transgene compensated for deficient endogenous EDNRB in these rats and prevented the development of congenital intestinal aganglionosis. The transgene had no effect on coat color spotting, indicating the critical time for EDNRB expression in ENS development begins after separation of the melanocyte lineage from the ENS lineage and a common precursor. The transgene dosage affected both the incidence and severity of the congenital intestinal defect, suggesting dosage-dependent events downstream of EDNRB activation in ENS development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9739043" 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="#36" class="mim-tip-reference" title="Shin, M. K., Russell, L. B., Tilghman, S. M. <strong>Molecular characterization of four induced alleles at the Ednrb locus.</strong> Proc. Nat. Acad. Sci. 94: 13105-13110, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9371807/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9371807</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9371807[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.94.24.13105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9371807">Shin et al. (1997)</a> attempted to identify the important domains for EDNRB function by studying 4 recessive juvenile lethal alleles in the mouse Ednrb gene created either by radiation or chemical mutagens. Molecular defects were identified in 3; in 1 mutation, which is associated with normal levels of Ednrb mRNA in adult brain, the mutation appeared to affect important regulatory elements that mediate the expression of the gene during development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9371807" 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>Lethal white foal syndrome (LWFS) is a congenital anomaly of horses resembling Hirschsprung disease characterized by a white coat color and aganglionosis of the bowel. To investigate the molecular basis of LWFS, <a href="#44" class="mim-tip-reference" title="Yang, G. C., Croaker, D., Zhang, A. L., Manglick, P., Cartmill, T., Cass, D. <strong>A dinucleotide mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome (LWFS); a horse variant of Hirschsprung disease (HSCR).</strong> Hum. Molec. Genet. 7: 1047-1052, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9580670/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9580670</a>] [<a href="https://doi.org/10.1093/hmg/7.6.1047" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9580670">Yang et al. (1998)</a> demonstrated that a full-length cDNA for horse EDNRB contains a 1,329-bp open reading frame that encoded 443 amino acid residues. The predicted amino acid sequence was 89%, 91%, and 85% identical to human, bovine, and mouse/rat EDNRB sequences, respectively, but only 55% identical to the human, bovine, and rat EDNRA sequences. When homozygous, a dinucleotide mutation, TC-to-AG, which changed isoleucine to lysine in the predicted first transmembrane domain of the EDNRB protein, was found as the basis of LWFS; the heterozygous state resulted in the 'overo' phenotype. The dinucleotide mutation involved nucleotides 353 and 354. It had previously been known that LWFS is produced most often by mating horses with the overo color pattern. One mutant allele produces the coat color change but the presence of at least 1 normal allele appears to protect against the development of aganglionosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9580670" 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="#26" class="mim-tip-reference" title="Metallinos, D. L., Bowling, A. T., Rine, J. <strong>A missense mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome: an equine version of Hirschsprung disease.</strong> Mammalian Genome 9: 426-431, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9585428/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9585428</a>] [<a href="https://doi.org/10.1007/s003359900790" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9585428">Metallinos et al. (1998)</a> also showed that an ile118-to-lys missense mutation in EDNRB is responsible for lethal white foal syndrome. Breedings between particular spotted horses, generally described as frame overo, produce some foals that, in contrast to their parents, are all white or nearly all white and die shortly after birth of severe intestinal blockage. These foals have aganglionosis characterized by a lack of submucosal and myenteric ganglia from the distal small intestine to the large intestine, similar to human Hirschsprung disease. <a href="#26" class="mim-tip-reference" title="Metallinos, D. L., Bowling, A. T., Rine, J. <strong>A missense mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome: an equine version of Hirschsprung disease.</strong> Mammalian Genome 9: 426-431, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9585428/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9585428</a>] [<a href="https://doi.org/10.1007/s003359900790" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9585428">Metallinos et al. (1998)</a> found that lethal white foal syndrome occurred in homozygotes; heterozygotes showed the frame overo pattern. Horses with tobiano markings included some carriers, indicating that tobiano is epistatic to frame overo. In addition, some horses identified as carriers had no recognized overo coat pattern phenotype, demonstrating the incomplete penetrance of the mutation. <a href="#33" class="mim-tip-reference" title="Santschi, E. M., Purdy, A. K., Valberg, S. J., Vrotsos, P. D., Kaese, H., Mickelson, J. R. <strong>Endothelin receptor B polymorphism associated with lethal white foal syndrome in horses.</strong> Mammalian Genome 9: 306-309, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9530628/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9530628</a>] [<a href="https://doi.org/10.1007/s003359900754" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9530628">Santschi et al. (1998)</a> likewise studied the ile118-to-lys change in the overo lethal white syndrome in foals born to American Paint Horse parents of the overo coat pattern lineage. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9585428+9530628" 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>To determine when EDNRB signaling is required during embryogenesis, <a href="#35" class="mim-tip-reference" title="Shin, M. K., Levorse, J. M., Ingram, R. S., Tilghman, S. M. <strong>The temporal requirement for endothelin receptor-B signalling during neural crest development.</strong> Nature 402: 496-501, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10591209/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10591209</a>] [<a href="https://doi.org/10.1038/990040" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10591209">Shin et al. (1999)</a> exploited the tetracycline-inducible system to generate strains of mice that expressed Ednrb at different stages of embryogenesis. <a href="#35" class="mim-tip-reference" title="Shin, M. K., Levorse, J. M., Ingram, R. S., Tilghman, S. M. <strong>The temporal requirement for endothelin receptor-B signalling during neural crest development.</strong> Nature 402: 496-501, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10591209/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10591209</a>] [<a href="https://doi.org/10.1038/990040" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10591209">Shin et al. (1999)</a> determined that Ednrb is required during a restricted period of neural crest development between embryonic days 10 and 12.5. <a href="#35" class="mim-tip-reference" title="Shin, M. K., Levorse, J. M., Ingram, R. S., Tilghman, S. M. <strong>The temporal requirement for endothelin receptor-B signalling during neural crest development.</strong> Nature 402: 496-501, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10591209/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10591209</a>] [<a href="https://doi.org/10.1038/990040" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10591209">Shin et al. (1999)</a> concluded that EDNRB is required for the migration of both melanoblasts and enteric neuroblasts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10591209" 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>The role of the endothelin-B receptor in vascular homeostasis is controversial because the receptor has both pressor and depressor effects in vivo. Spotting lethal rats carry a naturally occurring deletion in the endothelin-B receptor gene that completely abrogates functional receptor expression. Rats homozygous for this mutation die shortly after birth due to congenital distal intestinal aganglionosis. Genetic rescue of homozygous rats from this developmental defect using a dopamine hydroxylase-EDNRB transgene resulted in ETB-deficient adult rats <a href="#14" class="mim-tip-reference" title="Gariepy, C. E., Ohuchi, T., Williams, S. C., Richardson, J. A., Yanagisawa, M. <strong>Salt-sensitive hypertension in endothelin-B receptor-deficient rats.</strong> J. Clin. Invest. 105: 925-933, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10749572/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10749572</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10749572[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/10.1172/JCI8609" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10749572">Gariepy et al. (2000)</a>. On a sodium-deficient diet, the rats exhibited a normal arterial blood pressure, but on a high-sodium diet the homozygous sl rats became severely hypertensive. Normal pressure was restored in the salt-fed rats when the epithelial sodium channel was blocked with amiloride. <a href="#14" class="mim-tip-reference" title="Gariepy, C. E., Ohuchi, T., Williams, S. C., Richardson, J. A., Yanagisawa, M. <strong>Salt-sensitive hypertension in endothelin-B receptor-deficient rats.</strong> J. Clin. Invest. 105: 925-933, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10749572/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10749572</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10749572[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/10.1172/JCI8609" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10749572">Gariepy et al. (2000)</a> concluded that the rescued sl/sl rats are a novel single-locus genetic model of severe salt-sensitive hypertension. The results suggested that these rats are hypertensive because they lack the normal tonic inhibition of the renal epithelial sodium channel. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10749572" 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="#25" class="mim-tip-reference" title="Matsushima, Y., Shinkai, Y., Kobayashi, Y., Sakamoto, M., Kunieda, T., Tachibana, M. <strong>A mouse model of Waardenburg syndrome type 4 with a new spontaneous mutation of the endothelin-B receptor gene.</strong> Mammalian Genome 13: 30-35, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11773966/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11773966</a>] [<a href="https://doi.org/10.1007/s00335-001-3038-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11773966">Matsushima et al. (2002)</a> described a novel mutant mouse with a mutation in the Ednrb gene and proposed the mouse as an animal model of Waardenburg syndrome 4 (WS4; see <a href="/entry/277580">277580</a>), or Waardenburg-Shah syndrome, which combines Hirschsprung disease with features of Waardenburg syndrome. These mutants had a mixed genetic background and extensive white spotting. They died between 2 and 7 weeks after birth owing to megacolon; their colon distal to the megacolon lacked Auerbach plexus cells. These mutants did not respond to sound, and the stria vascularis of their cochleae lacked intermediate cells, i.e., neural crest-derived melanocytes. The inheritance was autosomal recessive as in human WS4. Breeding analysis revealed that WS4 mice are allelic with piebald-lethal and JF1 mice, which are also mutated in the Ednrb gene. Mutation analysis showed that the Ednrb gene lacked 318 nucleotides encoding transmembrane domains owing to deletion of exons 2 and 3. Interaction between endothelin-3 (<a href="/entry/131242">131242</a>) and its receptor is required for normal differentiation and development of melanocytes and Auerbach plexus cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11773966" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Carpenter, T., Schomberg, S., Steudel, W., Ozimek, J., Colvin, K., Stenmark, K., Ivy, D. D. <strong>Endothelin B receptor deficiency predisposes to pulmonary edema formation via increased lung vascular endothelial cell growth factor expression.</strong> Circ. Res. 93: 456-463, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12919946/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12919946</a>] [<a href="https://doi.org/10.1161/01.RES.0000090994.15442.42" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12919946">Carpenter et al. (2003)</a> studied pulmonary edema formation in EDNRB-deficient rats. In normoxia, EDNRB -/- rats had significantly more lung vascular leak than heterozygotes or controls. Hypoxia increased vascular leak regardless of genotype, and hypoxic EDNRB-deficient rats leaked more than hypoxic controls. EDNRB-deficient rats had higher lung endothelin levels in both normoxia and hypoxia. Lung hypoxia-inducible factor-1-alpha (HIF1A; <a href="/entry/603348">603348</a>) and vascular endothelial growth factor (VEGF; <a href="/entry/192240">192240</a>) levels were greater in the EDNRB-deficient rats in both normoxia and hypoxia, and both levels were reduced by EDNRA antagonism. Both EDNRA blockade and VEGF antagonism reduced vascular leak in hypoxic EDNRB-deficient rats. <a href="#8" class="mim-tip-reference" title="Carpenter, T., Schomberg, S., Steudel, W., Ozimek, J., Colvin, K., Stenmark, K., Ivy, D. D. <strong>Endothelin B receptor deficiency predisposes to pulmonary edema formation via increased lung vascular endothelial cell growth factor expression.</strong> Circ. Res. 93: 456-463, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12919946/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12919946</a>] [<a href="https://doi.org/10.1161/01.RES.0000090994.15442.42" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12919946">Carpenter et al. (2003)</a> concluded that EDNRB-deficient rats display an exaggerated lung vascular protein leak in normoxia, that hypoxia exacerbates that leak, and that this effect is in part attributable to an endothelin-mediated increase in lung VEGF content. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12919946" 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>Migration of the precursors of the enteric nervous system (ENS) into the colon requires expression of the EDNRB gene at a defined time. In studies in mice, <a href="#47" class="mim-tip-reference" title="Zhu, L., Lee, H.-O., Jordan, C. S., Cantrell, V. A., Southard-Smith, E. M., Shin, M. K. <strong>Spatiotemporal regulation of endothelin receptor-B by SOX10 in neural crest-derived enteric neuron precursors.</strong> Nature Genet. 36: 732-737, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15170213/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15170213</a>] [<a href="https://doi.org/10.1038/ng1371" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15170213">Zhu et al. (2004)</a> found a conserved spatiotemporal ENS enhancer of Ednrb. This 1-kb enhancer was activated as the ENS precursors approached the colon, and partial deletion of the enhancer at the endogenous Ednrb locus resulted in pigmented mice that died postnatally from megacolon. In the Ednrb ENS enhancer, they identified binding sites for Sox10 (<a href="/entry/602229">602229</a>), an SRY-related transcription factor associated with Hirschsprung disease, and mutational analyses of these sites suggested that SOX10 may have multiple roles in regulating EDNRB in the ENS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15170213" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Cantrell, V. A., Owens, S. E., Chandler, R. L., Airey, D. C., Bradley, K. M., Smith, J. R., Southard-Smith, E. M. <strong>Interactions between Sox10 and EdnrB modulate penetrance and severity of aganglionosis in the Sox10(Dom) mouse model of Hirschsprung disease.</strong> Hum. Molec. Genet. 13: 2289-2301, 2004. Note: Erratum: Hum. Molec. Genet. 13: 3241 only, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15294878/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15294878</a>] [<a href="https://doi.org/10.1093/hmg/ddh243" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15294878">Cantrell et al. (2004)</a> tested for association between genes in the endothelin signaling pathway and severity of aganglionosis in an extended pedigree of B6C3FeLe.Sox10(Dom) mice. Single-locus association analysis identified interaction between EdnrB and Sox10. Additional analysis of F2 intercross progeny confirmed a highly significant effect of EdnrB alleles on the Sox10(Dom/+) phenotype. The presence of C57BL/6J alleles at EdnrB was associated with increased penetrance and more severe aganglionosis in Sox10(Dom) mutants. Crosses between EdnrB and Sox10 mutants corroborated this gene interaction, with double-mutant progeny exhibiting significantly more severe aganglionosis. The background strain of the EdnrB mutant further influenced the phenotype of Sox10/EdnrB double-mutant progeny, implying the action of additional modifiers on this phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15294878" 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 adult transgenic mice with conditional cardiac-restricted ET1 overexpression, <a href="#45" class="mim-tip-reference" title="Yang, L. L., Gros, R., Kabir, M. G., Sadi, A., Gotlieb, A. I., Husain, M., Stewart, D. J. <strong>Conditional cardiac overexpression of endothelin-1 induces inflammation and dilated cardiomyopathy in mice.</strong> Circulation 109: 255-261, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14718401/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14718401</a>] [<a href="https://doi.org/10.1161/01.CIR.0000105701.98663.D4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14718401">Yang et al. (2004)</a> observed nuclear factor kappa-B (see <a href="/entry/164011">164011</a>) translocation, cytokine expression, inflammation and hypertrophy, resulting in dilated cardiomyopathy, congestive heart failure, and death as early as 5 weeks after transgene induction. Significant prolongation of survival was observed with a combined EDNRA/EDNRB antagonist but not with an EDNRA-selective antagonist, consistent with an important role for EDNRB in this model. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14718401" 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=RCV000018112 OR RCV000018113 OR RCV003236768" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018112, RCV000018113, RCV003236768" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018112...</a>
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<p>In an extensive Mennonite kindred with many cases of Hirschsprung disease (<a href="/entry/600155">600155</a>), <a href="#31" class="mim-tip-reference" title="Puffenberger, E. G., Hosoda, K., Washington, S. S., Nakao, K., deWit, D., Yanagisawa, M., Chakravarti, A. <strong>A missense mutation of the endothelin-B receptor gene in multigenic Hirschsprung's disease.</strong> Cell 79: 1257-1266, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8001158/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8001158</a>] [<a href="https://doi.org/10.1016/0092-8674(94)90016-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8001158">Puffenberger et al. (1994)</a> found a G-to-T missense mutation in exon 4 of the EDNRB gene, resulting in substitution of the highly conserved tryptophan-276 residue with a cysteine residue (W276C) in the fifth transmembrane helix of the G protein-coupled receptor. The mutant W276C receptor exhibited a partial impairment of ligand-induced Ca(2+) transient levels in transfected cells. HSCR was observed in 74% of W276C homozygotes and 21% of W276C heterozygotes. In addition to HSCR, nonenteric manifestations suggestive of Waardenburg-Shah syndrome (WS4A; <a href="/entry/277580">277580</a>) were observed in individuals with the mutation: bicolored irides in 6.3%, hypopigmentation in 2.5%, sensorineural hearing loss in 5.1%, and white forelock in 7.6%. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8001158" 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">rs104894388 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894388;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=rs104894388" 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=rs104894388" 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=RCV000018114" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018114" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018114</a>
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<p>In 2 girls born to consanguineous Tunisian parents, <a href="#3" class="mim-tip-reference" title="Attie, T., Till, M., Pelet, A., Amiel, J., Edery, P., Boutrand, L., Munnich, A., Lyonnet, S. <strong>Mutation of the endothelin-receptor B gene in Waardenburg-Hirschsprung disease.</strong> Hum. Molec. Genet. 4: 2407-2409, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8634719/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8634719</a>] [<a href="https://doi.org/10.1093/hmg/4.12.2407" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8634719">Attie et al. (1995)</a> described features of both Waardenburg syndrome and Hirschsprung disease (<a href="/entry/277580">277580</a>). They excluded RET and PAX3 (<a href="/entry/606597">606597</a>) as candidate genes by linkage analysis but found a homozygous missense mutation in exon 2 of the EDNRB gene. Using microsatellite DNA markers flanking the EDNRB gene, they showed that the 2 affected sibs were geno-identical and homozygous at these loci, whereas the 2 unaffected brothers shared no more than 1 allele with their affected sisters. The affected sisters showed an abnormal SSCP pattern in exon 2 and direct DNA sequencing revealed a C-to-G transversion at the second nucleotide of codon 183, predicted to result in the replacement of an alanine by a glycine (A183G) in the third transmembrane domain of EDNRB. The parents and 1 healthy brother who was studied were heterozygous for the A183G mutation. Neither affected sister had dystopia canthorum. However, both had deafness, white forelock, and heterochromia iridis, as well as Hirschsprung disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8634719" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104894389 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894389;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/rs104894389?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=rs104894389" 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=rs104894389" 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=RCV000018115" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018115" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018115</a>
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<p>In an isolated case of Hirschsprung disease (<a href="/entry/600155">600155</a>), <a href="#21" class="mim-tip-reference" title="Kusafuka, T., Wang, Y., Puri, P. <strong>Novel mutations of the endothelin-B receptor gene in isolated patients with Hirschsprung's disease.</strong> Hum. Molec. Genet. 5: 347-349, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8852658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8852658</a>] [<a href="https://doi.org/10.1093/hmg/5.3.347" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8852658">Kusafuka et al. (1996)</a> identified a G-to-A transition at nucleotide 824 of the EDNRB gene. The patient was heterozygous and apparently this represented a new mutation. Aganglionosis was confined to the rectosigmoid colon and there was no associated abnormality. The mutation converted a TGG (trp) codon to a stop codon at residue 275. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8852658" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 HIRSCHSPRUNG DISEASE, SUSCEPTIBILITY TO, 2</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> rs769735757 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs769735757;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/rs769735757?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=rs769735757" 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=rs769735757" 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=RCV000018116" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018116" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018116</a>
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<p>In an isolated case of Hirschsprung disease (<a href="/entry/600155">600155</a>), <a href="#21" class="mim-tip-reference" title="Kusafuka, T., Wang, Y., Puri, P. <strong>Novel mutations of the endothelin-B receptor gene in isolated patients with Hirschsprung's disease.</strong> Hum. Molec. Genet. 5: 347-349, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8852658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8852658</a>] [<a href="https://doi.org/10.1093/hmg/5.3.347" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8852658">Kusafuka et al. (1996)</a> found insertion of a T after nucleotide 878 in the EDNRB gene. The patient was heterozygous and presumably represented a new mutation, although no family studies were performed. The mutation caused a frameshift with early termination of translation at nucleotide 894. The aganglionosis was confined to the descending colon, and there were no associated abnormalities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8852658" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs1801710 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1801710;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/rs1801710?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=rs1801710" 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=rs1801710" 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=RCV000018117 OR RCV000216329 OR RCV000224294" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018117, RCV000216329, RCV000224294" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018117...</a>
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<p><a href="#37" class="mim-tip-reference" title="Svensson, P.-J., Anvret, M., Molander, M.-L., Nordenskjold, A. <strong>Phenotypic variation in a family with mutations in two Hirschsprung-related genes (RET and endothelin receptor B).</strong> Hum. Genet. 103: 145-148, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9760196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9760196</a>] [<a href="https://doi.org/10.1007/s004390050797" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9760196">Svensson et al. (1998)</a> described a family with Hirschsprung disease (<a href="/entry/600155">600155</a>) with missense mutations in both the RET gene (arg982 to cys; <a href="/entry/164761#0036">164761.0036</a>) and the EDNRB gene, gly57 to ser (G57S). In this family, 3 of 5 members had both mutations, but only 1, a boy, had the Hirschsprung disease phenotype. <a href="#17" class="mim-tip-reference" title="Hofstra, R. M. W., Osinga, J., Buys, C. H. C. M. <strong>Mutations in Hirschsprung disease: when does a mutation contribute to the phenotype?</strong> Europ. J. Hum. Genet. 5: 180-185, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9359036/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9359036</a>]" pmid="9359036">Hofstra et al. (1997)</a> found the G57S mutation in 3 of 40 HSCR patients, but also in 4 of 180 control chromosomes. With the controls studied by <a href="#37" class="mim-tip-reference" title="Svensson, P.-J., Anvret, M., Molander, M.-L., Nordenskjold, A. <strong>Phenotypic variation in a family with mutations in two Hirschsprung-related genes (RET and endothelin receptor B).</strong> Hum. Genet. 103: 145-148, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9760196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9760196</a>] [<a href="https://doi.org/10.1007/s004390050797" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9760196">Svensson et al. (1998)</a>, the figure comes to 4 of 410 control chromosomes. In the family of <a href="#37" class="mim-tip-reference" title="Svensson, P.-J., Anvret, M., Molander, M.-L., Nordenskjold, A. <strong>Phenotypic variation in a family with mutations in two Hirschsprung-related genes (RET and endothelin receptor B).</strong> Hum. Genet. 103: 145-148, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9760196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9760196</a>] [<a href="https://doi.org/10.1007/s004390050797" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9760196">Svensson et al. (1998)</a> the mother and a daughter carried both mutations; the G57S mutation was present in homozygous state in the daughter who had inherited the mutation from each parent. The fact that family members are healthy carriers of G57S in hetero- or homozygous form suggested a sex-dependent gene-dosage effect, comparable to that observed by <a href="#31" class="mim-tip-reference" title="Puffenberger, E. G., Hosoda, K., Washington, S. S., Nakao, K., deWit, D., Yanagisawa, M., Chakravarti, A. <strong>A missense mutation of the endothelin-B receptor gene in multigenic Hirschsprung's disease.</strong> Cell 79: 1257-1266, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8001158/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8001158</a>] [<a href="https://doi.org/10.1016/0092-8674(94)90016-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8001158">Puffenberger et al. (1994)</a> in a Mennonite kindred with the trp276-to-cys mutation (<a href="#0001">131244.0001</a>), in which there were heterozygous as well as homozygous healthy carriers of the founder mutation. The penetrance was higher in males, however. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8001158+9760196+9359036" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs5352 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs5352;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/rs5352?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=rs5352" 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=rs5352" 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=RCV000018118 OR RCV000222856 OR RCV000626404 OR RCV000659497 OR RCV000954472 OR RCV001258252" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018118, RCV000222856, RCV000626404, RCV000659497, RCV000954472, RCV001258252" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018118...</a>
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<p>In a patient with Hirschsprung disease (<a href="/entry/600155">600155</a>), <a href="#4" class="mim-tip-reference" title="Auricchio, A., Griseri, P., Carpentieri, M. L., Betsos, N., Staiano, A., Tozzi, A., Priolo, M., Thompson, H., Bocciardi, R., Romeo, G., Ballabio, A., Ceccherini, I. <strong>Double heterozygosity for a RET substitution inferring with splicing and an EDNRB missense mutation in Hirschsprung disease. (Letter)</strong> Am. J. Hum. Genet. 64: 1216-1221, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10090908/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10090908</a>] [<a href="https://doi.org/10.1086/302329" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10090908">Auricchio et al. (1999)</a> found double heterozygosity for a silent mutation, I647I, of the RET gene (<a href="/entry/164761#0037">164761.0037</a>), inherited from the unaffected mother, and an EDNRB missense mutation, S305N, transmitted by the healthy father. In 2 different patients they demonstrated both in vivo and in vitro that the silent RET mutation can interfere with correct transcription, possibly leading to a reduced level of the RET protein. The coexistence in the same patient of 2 functionally significant EDNRB and RET mutations suggested a direct genetic interaction between these 2 distinct transmembrane receptors in polygenic HSCR disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10090908" 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="#23" class="mim-tip-reference" title="Lek, M., Karczewski, K. J., Minikel, E. V., Samocha, K. E., Banks, E., Fennell, T., O'Donnell-Luria, A. H., Ware, J. S., Hill, A. J., Cummings, B. B., Tukiainen, T., Birnbaum, D. P., and 68 others. <strong>Analysis of protein-coding genetic variation in 60,706 humans.</strong> Nature 536: 285-291, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27535533/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27535533</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27535533[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature19057" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27535533">Lek et al. (2016)</a> questioned the validity of this variant as a susceptibility allele because it has a high global allele frequency (0.0089) in the ExAC database. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27535533" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0007 WAARDENBURG SYNDROME, TYPE 4A</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> rs104894390 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894390;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/rs104894390?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=rs104894390" 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=rs104894390" 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=RCV000018119 OR RCV001851902" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018119, RCV001851902" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018119...</a>
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<p>In a family with Waardenburg-Shah syndrome (<a href="/entry/277580">277580</a>), <a href="#38" class="mim-tip-reference" title="Syrris, P., Carter, N. D., Patton, M. A. <strong>Novel nonsense mutation of the endothelin-B receptor gene in a family with Waardenburg-Hirschsprung disease.</strong> Am. J. Med. Genet. 87: 69-71, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10528251/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10528251</a>]" pmid="10528251">Syrris et al. (1999)</a> identified a heterozygous C-to-T transition in exon 3 of the EDNRB gene, resulting in an arg253-to-ter (R253X) substitution resulting in premature termination. The mutation was not observed in over 50 unrelated controls. The data confirmed the role of EDNRB in the cause of Waardenburg-Shah disease and demonstrated that in this disorder there is a lack of correlation between phenotype and genotype and a variable expression of disease even within the same family. The family studied by <a href="#38" class="mim-tip-reference" title="Syrris, P., Carter, N. D., Patton, M. A. <strong>Novel nonsense mutation of the endothelin-B receptor gene in a family with Waardenburg-Hirschsprung disease.</strong> Am. J. Med. Genet. 87: 69-71, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10528251/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10528251</a>]" pmid="10528251">Syrris et al. (1999)</a> was of Afro-Caribbean origin and had a history of sensorineural deafness, heterochromia iridis, and Hirschsprung disease. Synophrys, hair or skin hypopigmentation, and dystopia canthorum were absent in this family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10528251" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0008 ABCD SYNDROME (1 family)</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> rs104894391 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894391;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/rs104894391?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=rs104894391" 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=rs104894391" 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=RCV000018120 OR RCV000659496 OR RCV001092078" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018120, RCV000659496, RCV001092078" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018120...</a>
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<p>In the fifth child affected with ABCD syndrome (<a href="/entry/600501">600501</a>) in a consanguineous Kurdish family, previously described by <a href="#16" class="mim-tip-reference" title="Gross, A., Kunze, J., Maier, R. F., Stoltenburg-Didinger, G., Grimmer, I., Obladen, M. <strong>Autosomal-recessive neural crest syndrome with albinism, black lock, cell migration disorder of the neurocytes of the gut, and deafness: ABCD syndrome.</strong> Am. J. Med. Genet. 56: 322-326, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7778600/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7778600</a>] [<a href="https://doi.org/10.1002/ajmg.1320560322" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7778600">Gross et al. (1995)</a>, <a href="#42" class="mim-tip-reference" title="Verheij, J. B. G. M., Kunze, J., Osinga, J., van Essen, A. J., Hofstra, R. M. W. <strong>ABCD syndrome is caused by a homozygous mutation in the EDNRB gene.</strong> Am. J. Med. Genet. 108: 223-225, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11891690/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11891690</a>] [<a href="https://doi.org/10.1002/ajmg.10172" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11891690">Verheij et al. (2002)</a> identified a homozygous C-to-T transition in exon 3 of the EDNRB gene, resulting in the substitution of a stop codon for an arginine residue (R201X). The affected female infant presented with bilateral deafness, albinism, a black lock at the right temporooccipital region, and spots of retinal depigmentation. She also had a severe defect of intestinal innervation from which she died at 5 weeks of age. <a href="#42" class="mim-tip-reference" title="Verheij, J. B. G. M., Kunze, J., Osinga, J., van Essen, A. J., Hofstra, R. M. W. <strong>ABCD syndrome is caused by a homozygous mutation in the EDNRB gene.</strong> Am. J. Med. Genet. 108: 223-225, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11891690/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11891690</a>] [<a href="https://doi.org/10.1002/ajmg.10172" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11891690">Verheij et al. (2002)</a> suggested that ABCD syndrome is not a separate entity, but an expression of Shah-Waardenburg syndrome (<a href="/entry/277580">277580</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11891690+7778600" 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">rs267606780 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606780;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=rs267606780" 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=rs267606780" 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=RCV000018121" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018121" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018121</a>
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<p>In a Spanish male patient with sporadic Hirschsprung disease (<a href="/entry/600155">600155</a>), <a href="#32" class="mim-tip-reference" title="Sanchez-Mejias, A., Fernandez, R. M., Lopez-Alonso, M., Antinolo, G., Borrego, S. <strong>New roles of EDNRB and EDN3 in the pathogenesis of Hirschsprung disease.</strong> Genet. Med. 12: 39-43, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20009762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20009762</a>] [<a href="https://doi.org/10.1097/GIM.0b013e3181c371b0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20009762">Sanchez-Mejias et al. (2010)</a> identified an A-to-T transversion at nucleotide 43 of the EDNRB gene, resulting in a lysine-to-termination substitution in codon 15 (K15X). This mutation was not identified in any other family members other than the father from whom the child inherited it. The father did not have Hirschsprung disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20009762" 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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Amiel, J., Attie, T., Jan, D., Pelet, A., Edery, P., Bidaud, C., Lacombe, D., Tam, P., Simeoni, J., Flori, E., Nihoul-Fekete, C., Munnich, A., Lyonnet, S.
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<strong>Heterozygous endothelin receptor B (EDNRB) mutations in isolated Hirschsprung disease.</strong>
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Hum. Molec. Genet. 5: 355-357, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8852660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8852660</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8852660" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/5.3.355" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Arai1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Arai, H., Nakao, K., Takaya, K., Hosoda, K., Ogawa, Y., Nakanishi, S., Imura, H.
|
|
<strong>The human endothelin-B receptor gene: structural organization and chromosomal assignment.</strong>
|
|
J. Biol. Chem. 268: 3463-3470, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8429023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8429023</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8429023" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Attie1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Attie, T., Till, M., Pelet, A., Amiel, J., Edery, P., Boutrand, L., Munnich, A., Lyonnet, S.
|
|
<strong>Mutation of the endothelin-receptor B gene in Waardenburg-Hirschsprung disease.</strong>
|
|
Hum. Molec. Genet. 4: 2407-2409, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8634719/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8634719</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8634719" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/4.12.2407" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Auricchio1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Auricchio, A., Griseri, P., Carpentieri, M. L., Betsos, N., Staiano, A., Tozzi, A., Priolo, M., Thompson, H., Bocciardi, R., Romeo, G., Ballabio, A., Ceccherini, I.
|
|
<strong>Double heterozygosity for a RET substitution inferring with splicing and an EDNRB missense mutation in Hirschsprung disease. (Letter)</strong>
|
|
Am. J. Hum. Genet. 64: 1216-1221, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10090908/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10090908</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10090908" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/302329" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Bourgeois1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bourgeois, C., Robert, B., Rebourcet, R., Mondon, F., Mignot, T.-M., Duc-Goiran, P., Ferre, F.
|
|
<strong>Endothelin-1 and ET(A) receptor expression in vascular smooth muscle cells from human placenta: a new ET(A) receptor messenger ribonucleic acid is generated by alternative splicing of exon 3.</strong>
|
|
J. Clin. Endocr. Metab. 82: 3116-3123, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9284755/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9284755</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9284755" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.82.9.4209" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Buckanovich2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Buckanovich, R. J., Facciabene, A., Kim, S., Benencia, F., Sasaroli, D., Balint, K., Katsaros, D., O'Brien-Jenkins, A., Gimotty, P. A., Coukos, G.
|
|
<strong>Endothelin B receptor mediates the endothelial barrier to T cell homing to tumors and disables immune therapy.</strong>
|
|
Nature Med. 14: 28-36, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18157142/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18157142</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18157142" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nm1699" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Cantrell2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cantrell, V. A., Owens, S. E., Chandler, R. L., Airey, D. C., Bradley, K. M., Smith, J. R., Southard-Smith, E. M.
|
|
<strong>Interactions between Sox10 and EdnrB modulate penetrance and severity of aganglionosis in the Sox10(Dom) mouse model of Hirschsprung disease.</strong>
|
|
Hum. Molec. Genet. 13: 2289-2301, 2004. Note: Erratum: Hum. Molec. Genet. 13: 3241 only, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15294878/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15294878</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15294878" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddh243" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Carpenter2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Carpenter, T., Schomberg, S., Steudel, W., Ozimek, J., Colvin, K., Stenmark, K., Ivy, D. D.
|
|
<strong>Endothelin B receptor deficiency predisposes to pulmonary edema formation via increased lung vascular endothelial cell growth factor expression.</strong>
|
|
Circ. Res. 93: 456-463, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12919946/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12919946</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12919946" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1161/01.RES.0000090994.15442.42" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Carrasquillo2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Carrasquillo, M. M., McCallion, A. S., Puffenberger, E. G., Kashuk, C. S., Nouri, N., Chakravarti, A.
|
|
<strong>Genome-wide association study and mouse model identify interaction between RET and EDNRB pathways in Hirschsprung disease.</strong>
|
|
Nature Genet. 32: 237-244, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12355085/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12355085</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12355085" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng998" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Ceccherini1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ceccherini, I., Zhang, A. L., Matera, I., Yang, G., Devoto, M., Romeo, G., Cass, D. T.
|
|
<strong>Interstitial deletion of the endothelin-B receptor gene in the spotting lethal (sl) rat.</strong>
|
|
Hum. Molec. Genet. 4: 2089-2096, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8589685/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8589685</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8589685" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/4.11.2089" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Chakravarti1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chakravarti, A.
|
|
<strong>Endothelin receptor-mediated signaling in Hirschsprung disease.</strong>
|
|
Hum. Molec. Genet. 5: 303-307, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8852653/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8852653</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8852653" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Elshourbagy1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Elshourbagy, N. A., Adamou, J. E., Gagnon. A. W., Wu, H.-L., Pullen, M., Nambi, P.
|
|
<strong>Molecular characterization of a novel human endothelin receptor splice variant.</strong>
|
|
J. Biol. Chem. 271: 25300-25307, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8810293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8810293</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8810293" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.271.41.25300" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Gariepy1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gariepy, C. E., Cass, D. T., Yanagisawa, M.
|
|
<strong>Null mutation of endothelin receptor type B gene in spotting lethal rats causes aganglionic megacolon and white coat color.</strong>
|
|
Proc. Nat. Acad. Sci. 93: 867-872, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8570650/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8570650</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8570650" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.93.2.867" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Gariepy2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gariepy, C. E., Ohuchi, T., Williams, S. C., Richardson, J. A., Yanagisawa, M.
|
|
<strong>Salt-sensitive hypertension in endothelin-B receptor-deficient rats.</strong>
|
|
J. Clin. Invest. 105: 925-933, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10749572/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10749572</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10749572[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=10749572" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI8609" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Gariepy1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gariepy, C. E., Williams, S. C., Richardson, J. A., Hammer, R. E., Yanagisawa, M.
|
|
<strong>Transgenic expression of the endothelin-B receptor prevents congenital intestinal aganglionosis in a rat model of Hirschsprung disease.</strong>
|
|
J. Clin. Invest. 102: 1092-1101, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9739043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9739043</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9739043" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI3702" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Gross1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gross, A., Kunze, J., Maier, R. F., Stoltenburg-Didinger, G., Grimmer, I., Obladen, M.
|
|
<strong>Autosomal-recessive neural crest syndrome with albinism, black lock, cell migration disorder of the neurocytes of the gut, and deafness: ABCD syndrome.</strong>
|
|
Am. J. Med. Genet. 56: 322-326, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7778600/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7778600</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7778600" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.1320560322" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Hofstra1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hofstra, R. M. W., Osinga, J., Buys, C. H. C. M.
|
|
<strong>Mutations in Hirschsprung disease: when does a mutation contribute to the phenotype?</strong>
|
|
Europ. J. Hum. Genet. 5: 180-185, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9359036/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9359036</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9359036" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Hosoda1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hosoda, K., Hammer, R. E., Richardson, J. A., Baynash, A. G., Cheung, J. C., Giaid, A., Yanagisawa, M.
|
|
<strong>Targeted and natural (piebald-lethal) mutations of endothelin-B receptor gene produce megacolon associated with spotted coat color in mice.</strong>
|
|
Cell 79: 1267-1276, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8001159/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8001159</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8001159" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0092-8674(94)90017-5" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Iwashita2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Iwashita, T., Kruger, G. M., Pardal, R., Kiel, M. J., Morrison, S. J.
|
|
<strong>Hirschsprung disease is linked to defects in neural crest stem cell function.</strong>
|
|
Science 301: 972-976, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12920301/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12920301</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12920301[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=12920301" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1085649" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Khodorova2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Khodorova, A., Navarro, B., Jouaville, L. S., Murphy, J.-E., Rice, F. I., Mazurkiewicz, J. E., Long-Woodward, D., Stoffel, M., Strichartz, G. R., Yukhananov, R., Davar, G.
|
|
<strong>Endothelin-B receptor activation triggers an endogenous analgesic cascade at sites of peripheral injury.</strong>
|
|
Nature Med. 9: 1055-1061, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12847519/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12847519</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12847519" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nm885" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Kusafuka1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kusafuka, T., Wang, Y., Puri, P.
|
|
<strong>Novel mutations of the endothelin-B receptor gene in isolated patients with Hirschsprung's disease.</strong>
|
|
Hum. Molec. Genet. 5: 347-349, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8852658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8852658</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8852658" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/5.3.347" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Lane1966" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lane, P. W.
|
|
<strong>Association of megacolon with two recessive spotting genes in the mouse.</strong>
|
|
J. Hered. 57: 29-31, 1966.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5917257/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5917257</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5917257" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/oxfordjournals.jhered.a107457" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Lek2016" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lek, M., Karczewski, K. J., Minikel, E. V., Samocha, K. E., Banks, E., Fennell, T., O'Donnell-Luria, A. H., Ware, J. S., Hill, A. J., Cummings, B. B., Tukiainen, T., Birnbaum, D. P., and 68 others.
|
|
<strong>Analysis of protein-coding genetic variation in 60,706 humans.</strong>
|
|
Nature 536: 285-291, 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27535533/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27535533</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27535533[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=27535533" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature19057" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Maggi2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Maggi, M., Barni, T., Fantoni, G., Mancina, R., Pupilli, C., Luconi, M., Crescioli, C., Serio, M., Vannelli, G. B.
|
|
<strong>Expression and biological effects of endothelin-1 in human gonadotropin-releasing hormone-secreting neurons.</strong>
|
|
J. Clin. Endocr. Metab. 85: 1658-1665, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10770212/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10770212</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10770212" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.85.4.6565" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Matsushima2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Matsushima, Y., Shinkai, Y., Kobayashi, Y., Sakamoto, M., Kunieda, T., Tachibana, M.
|
|
<strong>A mouse model of Waardenburg syndrome type 4 with a new spontaneous mutation of the endothelin-B receptor gene.</strong>
|
|
Mammalian Genome 13: 30-35, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11773966/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11773966</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11773966" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s00335-001-3038-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Metallinos1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Metallinos, D. L., Bowling, A. T., Rine, J.
|
|
<strong>A missense mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome: an equine version of Hirschsprung disease.</strong>
|
|
Mammalian Genome 9: 426-431, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9585428/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9585428</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9585428" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s003359900790" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Nakamuta1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nakamuta, M., Takayanagi, R., Sakai, Y., Sakamoto, S., Hagiwara, H., Mizuno, T., Saito, Y., Hirose, S., Yamamoto, M., Nawata, H.
|
|
<strong>Cloning and sequence analysis of a cDNA encoding human non-selective type of endothelin receptor.</strong>
|
|
Biochem. Biophys. Res. Commun. 177: 34-39, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1710450/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1710450</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1710450" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0006-291x(91)91944-8" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Ogawa1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ogawa, Y., Nakao, K., Arai, H., Nakagawa, O., Hosoda, K., Suga, S., Nakanishi, S., Imura, H.
|
|
<strong>Molecular cloning of a non-isopeptide-selective human endothelin receptor.</strong>
|
|
Biochem. Biophys. Res. Commun. 178: 248-255, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1648908/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1648908</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1648908" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0006-291x(91)91806-n" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Okafor2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Okafor, M. C., Delamere, N. A.
|
|
<strong>The inhibitory influence of endothelin on active sodium-potassium transport in porcine lens.</strong>
|
|
Invest. Ophthal. Vis. Sci. 42: 1018-1023, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11274080/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11274080</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11274080" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Pao2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pao, M. M., Tsutsumi, M., Liang, G., Uzvolgyi, E., Gonzales, F. A., Jones, P. A.
|
|
<strong>The endothelin receptor B (EDNRB) promoter displays heterogeneous, site specific methylation patterns in normal and tumor cells.</strong>
|
|
Hum. Molec. Genet. 10: 903-910, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11309363/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11309363</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11309363" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/10.9.903" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Puffenberger1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Puffenberger, E. G., Hosoda, K., Washington, S. S., Nakao, K., deWit, D., Yanagisawa, M., Chakravarti, A.
|
|
<strong>A missense mutation of the endothelin-B receptor gene in multigenic Hirschsprung's disease.</strong>
|
|
Cell 79: 1257-1266, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8001158/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8001158</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8001158" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0092-8674(94)90016-7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Sanchez-Mejias2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sanchez-Mejias, A., Fernandez, R. M., Lopez-Alonso, M., Antinolo, G., Borrego, S.
|
|
<strong>New roles of EDNRB and EDN3 in the pathogenesis of Hirschsprung disease.</strong>
|
|
Genet. Med. 12: 39-43, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20009762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20009762</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20009762" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1097/GIM.0b013e3181c371b0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Santschi1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Santschi, E. M., Purdy, A. K., Valberg, S. J., Vrotsos, P. D., Kaese, H., Mickelson, J. R.
|
|
<strong>Endothelin receptor B polymorphism associated with lethal white foal syndrome in horses.</strong>
|
|
Mammalian Genome 9: 306-309, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9530628/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9530628</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9530628" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s003359900754" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Shihoya2016" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shihoya, W., Nishizawa, T., Okuta, A., Tani, K., Dohmae, N., Fujiyoshi, Y., Nureki, O., Doi, T.
|
|
<strong>Activation mechanism of endothelin ET(B) receptor by endothelin-1.</strong>
|
|
Nature 537: 363-368, 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27595334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27595334</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27595334" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature19319" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Shin1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shin, M. K., Levorse, J. M., Ingram, R. S., Tilghman, S. M.
|
|
<strong>The temporal requirement for endothelin receptor-B signalling during neural crest development.</strong>
|
|
Nature 402: 496-501, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10591209/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10591209</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10591209" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/990040" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Shin1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shin, M. K., Russell, L. B., Tilghman, S. M.
|
|
<strong>Molecular characterization of four induced alleles at the Ednrb locus.</strong>
|
|
Proc. Nat. Acad. Sci. 94: 13105-13110, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9371807/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9371807</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9371807[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=9371807" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.94.24.13105" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Svensson1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Svensson, P.-J., Anvret, M., Molander, M.-L., Nordenskjold, A.
|
|
<strong>Phenotypic variation in a family with mutations in two Hirschsprung-related genes (RET and endothelin receptor B).</strong>
|
|
Hum. Genet. 103: 145-148, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9760196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9760196</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9760196" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s004390050797" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Syrris1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Syrris, P., Carter, N. D., Patton, M. A.
|
|
<strong>Novel nonsense mutation of the endothelin-B receptor gene in a family with Waardenburg-Hirschsprung disease.</strong>
|
|
Am. J. Med. Genet. 87: 69-71, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10528251/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10528251</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10528251" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" class="mim-anchor"></a>
|
|
<a id="Takayanagi1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Takayanagi, R., Ohnaka, K., Takasaki, C., Ohashi, M., Nawata, H.
|
|
<strong>Multiple subtypes of endothelin receptors in porcine tissues: characterization by ligand binding, affinity labeling and regional distribution.</strong>
|
|
Regul. Pept. 32: 23-37, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1848367/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1848367</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1848367" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0167-0115(91)90004-z" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Tanaka1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tanaka, H., Moroi, K., Iwai, J., Takahashi, H., Ohnuma, N., Hori, S., Takimoto, M., Nishiyama, M., Masaki, T., Yanagisawa, M., Sekiya, S., Kimura, S.
|
|
<strong>Novel mutations of the endothelin B receptor gene in patients with Hirschsprung's disease and their characterization.</strong>
|
|
J. Biol. Chem. 273: 11378-11383, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9556633/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9556633</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9556633" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.273.18.11378" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="41" class="mim-anchor"></a>
|
|
<a id="Vane1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vane, J. R.
|
|
<strong>Endothelins come home to roost.</strong>
|
|
Nature 348: 673, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2175394/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2175394</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2175394" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/348673a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Verheij2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
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|
|
Verheij, J. B. G. M., Kunze, J., Osinga, J., van Essen, A. J., Hofstra, R. M. W.
|
|
<strong>ABCD syndrome is caused by a homozygous mutation in the EDNRB gene.</strong>
|
|
Am. J. Med. Genet. 108: 223-225, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11891690/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11891690</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11891690" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.10172" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="43" class="mim-anchor"></a>
|
|
<a id="Wang2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wang, L., Fortune, B., Cull, G., Dong, J., Cioffi, G. A.
|
|
<strong>Endothelin B receptor in human glaucoma and experimentally induced optic nerve damage.</strong>
|
|
Arch. Ophthal. 124: 717-724, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16682595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16682595</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16682595" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
|
|
|
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[<a href="https://doi.org/10.1001/archopht.124.5.717" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="44" class="mim-anchor"></a>
|
|
<a id="Yang1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yang, G. C., Croaker, D., Zhang, A. L., Manglick, P., Cartmill, T., Cass, D.
|
|
<strong>A dinucleotide mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome (LWFS); a horse variant of Hirschsprung disease (HSCR).</strong>
|
|
Hum. Molec. Genet. 7: 1047-1052, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9580670/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9580670</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9580670" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
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[<a href="https://doi.org/10.1093/hmg/7.6.1047" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
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|
|
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|
|
|
|
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|
|
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|
|
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|
|
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|
|
<p class="mim-text-font">
|
|
Yang, L. L., Gros, R., Kabir, M. G., Sadi, A., Gotlieb, A. I., Husain, M., Stewart, D. J.
|
|
<strong>Conditional cardiac overexpression of endothelin-1 induces inflammation and dilated cardiomyopathy in mice.</strong>
|
|
Circulation 109: 255-261, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14718401/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14718401</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14718401" 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/10.1161/01.CIR.0000105701.98663.D4" target="_blank">Full Text</a>]
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|
|
|
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|
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|
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|
|
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|
|
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|
|
Zeidel, M. L., Brady, H. R., Kone, B. C., Gullans, S. R., Brenner, B. M.
|
|
<strong>Endothelin, a peptide inhibitor of Na(+)-K(+)-ATPase in intact renal tubular epithelial cells.</strong>
|
|
Am. J. Physiol. 257: C1101-C1107, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2558568/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2558568</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2558568" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1152/ajpcell.1989.257.6.C1101" target="_blank">Full Text</a>]
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|
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|
|
|
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|
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|
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|
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Zhu, L., Lee, H.-O., Jordan, C. S., Cantrell, V. A., Southard-Smith, E. M., Shin, M. K.
|
|
<strong>Spatiotemporal regulation of endothelin receptor-B by SOX10 in neural crest-derived enteric neuron precursors.</strong>
|
|
Nature Genet. 36: 732-737, 2004.
|
|
|
|
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15170213/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15170213</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15170213" 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/ng1371" target="_blank">Full Text</a>]
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Ada Hamosh - updated : 11/30/2016
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<span class="mim-text-font">
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Ada Hamosh - updated : 09/27/2016<br>Ada Hamosh - updated : 5/27/2010<br>Paul J. Converse - updated : 3/5/2008<br>George E. Tiller - updated : 4/5/2007<br>Jane Kelly - updated : 12/7/2006<br>Marla J. F. O'Neill - updated : 11/11/2005<br>Victor A. McKusick - updated : 7/7/2004<br>Marla J. F. O'Neill - updated : 3/12/2004<br>Ada Hamosh - updated : 8/26/2003<br>Victor A. McKusick - updated : 7/1/2003<br>Victor A. McKusick - updated : 9/25/2002<br>Victor A. McKusick - updated : 5/23/2002<br>Deborah L. Stone - updated : 4/25/2002<br>Jane Kelly - updated : 1/25/2002<br>George E. Tiller - updated : 9/28/2001<br>John A. Phillips, III - updated : 12/1/2000<br>Ada Hamosh - updated : 2/1/2000<br>Victor A. McKusick - updated : 11/23/1999<br>Victor A. McKusick - updated : 4/9/1999<br>Victor A. McKusick - updated : 3/11/1999<br>Victor A. McKusick - updated : 10/29/1998<br>Victor A. McKusick - updated : 10/6/1998<br>Victor A. McKusick - updated : 9/4/1998<br>Victor A. McKusick - updated : 7/30/1998<br>Victor A. McKusick - updated : 6/15/1998<br>Victor A. McKusick - updated : 2/24/1998<br>John A. Phillips, III - updated : 10/6/1997<br>Jennifer P. Macke - updated : 5/20/1997
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Victor A. McKusick : 7/12/1991
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carol : 09/24/2022<br>carol : 04/19/2022<br>carol : 12/01/2016<br>carol : 11/30/2016<br>alopez : 09/27/2016<br>carol : 09/18/2013<br>terry : 3/28/2013<br>carol : 6/1/2011<br>wwang : 5/12/2011<br>carol : 7/29/2010<br>alopez : 6/2/2010<br>terry : 5/27/2010<br>ckniffin : 3/15/2010<br>carol : 3/11/2010<br>ckniffin : 3/8/2010<br>mgross : 3/5/2008<br>alopez : 12/5/2007<br>alopez : 4/13/2007<br>terry : 4/5/2007<br>carol : 12/7/2006<br>terry : 12/7/2006<br>wwang : 11/11/2005<br>alopez : 7/9/2004<br>terry : 7/7/2004<br>tkritzer : 3/30/2004<br>ckniffin : 3/16/2004<br>tkritzer : 3/12/2004<br>alopez : 8/29/2003<br>alopez : 8/26/2003<br>terry : 8/26/2003<br>alopez : 7/2/2003<br>terry : 7/1/2003<br>alopez : 9/25/2002<br>alopez : 9/25/2002<br>alopez : 9/25/2002<br>tkritzer : 9/23/2002<br>alopez : 5/28/2002<br>terry : 5/23/2002<br>carol : 4/25/2002<br>terry : 4/25/2002<br>carol : 1/29/2002<br>terry : 1/25/2002<br>carol : 1/8/2002<br>cwells : 10/9/2001<br>cwells : 9/28/2001<br>mgross : 12/1/2000<br>mcapotos : 6/9/2000<br>mcapotos : 6/8/2000<br>alopez : 2/2/2000<br>terry : 2/1/2000<br>carol : 11/29/1999<br>terry : 11/23/1999<br>carol : 4/12/1999<br>terry : 4/9/1999<br>carol : 3/29/1999<br>terry : 3/11/1999<br>psherman : 2/15/1999<br>carol : 1/4/1999<br>carol : 11/2/1998<br>terry : 10/29/1998<br>carol : 10/12/1998<br>terry : 10/6/1998<br>alopez : 9/9/1998<br>carol : 9/4/1998<br>carol : 8/3/1998<br>terry : 7/30/1998<br>carol : 7/8/1998<br>dkim : 7/2/1998<br>alopez : 6/17/1998<br>terry : 6/15/1998<br>alopez : 2/25/1998<br>terry : 2/24/1998<br>jenny : 12/1/1997<br>jenny : 11/17/1997<br>alopez : 8/12/1997<br>alopez : 7/25/1997<br>alopez : 7/25/1997<br>mark : 4/17/1996<br>terry : 4/10/1996<br>mark : 2/9/1996<br>terry : 2/8/1996<br>mark : 1/18/1996<br>terry : 1/16/1996<br>mark : 1/16/1996<br>mark : 1/10/1996<br>terry : 1/26/1995<br>carol : 3/20/1993<br>supermim : 3/16/1992<br>carol : 2/20/1992<br>carol : 9/12/1991
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<div class="container visible-print-block">
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<h3>
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<span class="mim-font">
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<strong>*</strong> 131244
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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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ENDOTHELIN RECEPTOR, TYPE B; EDNRB
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</span>
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</h3>
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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-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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ENDOTHELIN RECEPTOR, NONSELECTIVE TYPE; ETB<br />
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ETRB; ETBR
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</span>
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</h4>
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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: EDNRB</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> 715952000;
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</span>
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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: 13q22.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 13:77,895,487-77,975,527 </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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<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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13q22.3
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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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?ABCD 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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600501
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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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{Hirschsprung disease, susceptibility to, 2}
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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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600155
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant
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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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Waardenburg syndrome, type 4A
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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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277580
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant; Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Endothelins belong to a family of potent vasoactive peptides consisting of 3 isopeptides, ET1 (EDN1; 131240), ET2 (EDN2; 131241), and ET3 (EDN3; 131242). A diverse set of pharmacologic activities with different potencies are exerted by endothelin family peptides, suggesting the existence of ET receptor subtypes. Takayanagi et al. (1991) described 2 distinct subclasses of ET receptors, namely, ET1-specific and ET-nonselective. Vane (1990) recommended that the ET1-specific type be called ETA and the nonselective type ETB. Nakamuta et al. (1991) isolated a cDNA encoding human ETB receptor from a cDNA library constructed from human liver. Hepatocytes have a considerable number of ET receptors linked to biologic actions such as glycogenolysis. The cDNA had an open reading frame encoding a protein of 442 amino acid residues with a relative mass of 49,643. The deduced amino acid sequence of the human ETB receptor was 88% and 64% identical to those of rat lung ETB receptor and bovine lung ET1-specific receptor, respectively. Ogawa et al. (1991) likewise isolated a nonisopeptide-selective human endothelin receptor from a human placenta cDNA library. The predicted protein had 442 amino acids with a transmembrane topology similar to that of other G protein-coupled receptors. </p><p>Elshourbagy et al. (1996) isolated a novel splice variant of the endothelin-B receptor which they termed ETB-SVR. The sequence of the ETB-SVR receptor is identical to ETRB except for the intracellular C-terminal domain. The ETB-SVR receptor is expressed as a 2.7-kb mRNA in the lung, placenta, kidney, and skeletal muscle. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Elshourbagy et al. (1996) transfected COS cells with ETB-SVR or ETRB and found that both receptors bind to ET1. However, while ETRB-transfected cells responded to ET1 with increases in inositol phosphate accumulation and intracellular acidification, ETB-SVR-transfected cells did not exhibit either of these responses to ET1. These data suggested to Elshourbagy et al. (1996) that ETB-SVR and ETRB are functionally distinct, and that the difference in the C-terminal amino acid sequences determines functional coupling. </p><p>To investigate the influence of pregnancy-specific hormonal environment on expression of ET1 and ET1 receptor (EDNRA; 131243), Bourgeois et al. (1997) investigated whether the muscular layer of stem villi vessels could be a site of the ET1 expression. The authors found that whereas both EDNRA and EDNRB are present in stem villi vessels, placental vascular smooth muscle cells exclusively express the EDNRA. </p><p>Maggi et al. (2000) demonstrated that in FNC-B4 cells, which are derived from a human fetal olfactory epithelium, both sex steroids and odorants regulate GnRH secretion. They found biologic activity of EDN1 in this GnRH-secreting neuronal cell. In situ hybridization and immunohistochemistry revealed gene and protein expression of EDN1 and its converting enzyme (ECE1; 600423) in both fetal olfactory mucosa and FNC-B4 cells. Experiments with radiolabeled EDN1 and EDN3 strongly indicated the presence of 2 classes of binding sites, corresponding to the ETA (16,500 sites/cell) and the ETB receptors (8,700 sites/cell). Functional studies using selective analogs indicated that these 2 classes of receptors subserve distinct functions in human GnRH-secreting cells. The ETA receptor subtype mediated an increase in intracellular calcium and GnRH secretion. </p><p>Endothelin-1 inhibits active Na-K transport by as much as 50% in the renal tubule and other tissues (Zeidel et al., 1989). Okafor and Delamere (2001) noted that the presence of low levels of ET1 in aqueous humor combined with the potential for release of ET1 from ciliary processes suggested that the crystalline lens could be exposed to ET1 in vivo. They studied the influence of ET1 on active Na-K transport in the porcine lens. Their results suggested that ET1 inhibited active lens Na-K transport by activating EDNRA and EDNRB. Activation of the ET receptors also caused an increase in cytoplasmic calcium concentration in cultured lens epithelial cells. Both responses to ET1 appear to have a tyrosine kinase step. </p><p>The 5-prime region of EDNRB is a complex CpG island giving rise to 4 individual transcripts initiating within the island. Pao et al. (2001) analyzed the relationship between methylation and EDNRB expression in human tissues. The CpG island was unmethylated in normal prostate and bladder tissue, whereas it was methylated in colonic epithelium; DNA from tumors derived from these tissues was frequently hypermethylated. Analysis of 11 individual CpG sites in the CpG island showed that specific sites with high methylation levels in several tumors and cancer cell lines were also methylated in normal tissues, suggesting that these sites might serve as foci for further de novo methylation. A low methylation level in a small region within the 5-prime region correlated with expression of the 5-prime-most transcript, whereas almost complete methylation 200 to 1000 bp downstream of the transcriptional start site did not block expression of this transcript. Treatment with 5-aza-2-prime-deoxycytidine induced transcriptional activation of all 4 EDNRB transcripts. The authors concluded that there is differential, tissue-dependent methylation at the EDNRB 5-prime region, and that hypermethylation immediately 3-prime to the transcriptional start site does not prevent initiation. They further proposed a spreading mechanism for de novo methylation, starting from particular methylation hotspots. </p><p>Endothelin-1 is synthesized by keratinocytes in normal skin and is locally released after cutaneous injury. It is able to trigger pain through its actions on endothelin-A receptors of local nociceptors, but coincidentally produces analgesia through endothelin-B receptors. Khodorova et al. (2003) mapped an endogenous analgesic circuit, in which endothelin-B receptor activation induces the release of beta-endorphin from keratinocytes and the activation of G protein-coupled inwardly rectifying potassium channels (GIRKs, also called Kir-3) linked to opioid receptors on nociceptors. These results indicated the existence of an intrinsic feedback mechanism to control peripheral pain in skin, and established keratinocytes as an endothelin-B receptor-operated opioid pool. </p><p>Using gene expression profiling, Iwashita et al. (2003) determined that genes associated with Hirschsprung disease were highly upregulated in rat gut neural crest stem cells relative to whole-fetus RNA. The genes with highest expression were GDNF (600837), SOX10 (602229), GFRA1 (601496), and EDNRB. The highest expression was seen in RET (164761), which was found to be necessary for neural crest stem cell migration in the gut. GDNF promoted the migration of neural crest stem cells in culture but did not affect their survival or proliferation. The observations made by Iwashita et al. (2003) were confirmed by quantitative RT-PCR, flow cytometry, and functional analysis. </p><p>Wang et al. (2006) assessed EDNRB expression in human glaucomatous optic nerves and the spatial relationship between EDNRB and astrocytes. The frequency of positive EDNRB immunoreactivity was significantly higher in human glaucomatous optic nerves as compared with age-matched controls (9/16 vs 1/10). EDNRB colocalized with astrocytic processes and was quantitatively higher in the glaucomatous eyes. Wang et al. (2006) concluded that increased EDNRB immunoreactivity in diseased optic nerves and its association with astrocytes suggested that the glia-endothelin system might be involved in the pathologic mechanisms of neuronal degeneration. </p><p>Using transcription profiling of microdissected tumor endothelial cells from human ovarian cancers, Buckanovich et al. (2008) found that overexpression of ETBR was associated with absence of tumor-infiltrating lymphocytes and short patient survival time. An ETBR inhibitor increased adhesion of T cells to human endothelium in vitro, and this effect was countered by ICAM1 (147840) blockade or treatment with nitric oxide donors. Mice treated with the ETBR inhibitor displayed increased Icam1-dependent T-cell homing to tumors. ETBR inhibitor treatment enabled a tumor response in otherwise ineffective immunotherapy without altering the systemic antitumor immune response. Buckanovich et al. (2008) proposed that mixed ETAR-ETBR blockade could simultaneously target tumor cells through ETAR and enhance antitumor immune mechanisms through vascular ETBR. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Arai et al. (1993) demonstrated that the human genome contains a single copy of the ETRB gene, which spans 24 kb and comprises 7 exons and 6 introns. Every intron occurs near the border of the putative transmembrane domain in the coding region. </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>Using human/rodent somatic hybrid cell lines, Arai et al. (1993) assigned the ETRB gene to human chromosome 13. </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>Biochemical Features</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>Crystal Structure</em></strong></p><p>
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Shihoya et al. (2016), reported the crystal structures of human endothelin type B receptor in the ligand-free form and in complex with the endogenous agonist endothelin-1 (131240). The structures and mutation analysis revealed the mechanism for the isopeptide selectivity between endothelin-1 and -3. Transmembrane helices 1, 2, 6, and 7 move and envelop the entire endothelin peptide in a virtually irreversible manner. The agonist-induced conformational changes are propagated to the receptor core and the cytoplasmic G protein-coupling interface, and probably induce conformational flexibility in TM6. A comparison with the M2 muscarinic receptor (CHRM2; 118493) suggested a shared mechanism for signal transduction in class A G protein-coupled receptors. </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>Susceptibility to Hirschsprung Disease 2</em></strong></p><p>
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Puffenberger et al. (1994) presented evidence that Hirschsprung disease (HSCR2; 600155), an apparently multigenic disorder, can result in some cases from mutation in the endothelin-B receptor gene. EDNRB was a candidate gene because it mapped to the same region of chromosome 13 as did HSCR2. A trp276-to-cys mutation (W276C; 131244.0001) was dosage sensitive in that homozygotes and heterozygotes had a 74% and a 21% risk, respectively, of developing HSCR. For all clinical forms of HSCR, there is a greater incidence of megacolon in males than in females and the same was true for the specific EDNRB mutation. However, among the Mennonites, at least 5 megacolon patients did not seem to carry the W276C EDNRB mutation present in most of the affected members, which suggested the existence of as yet undiscovered HSCR susceptibility genes. </p><p>Kusafuka et al. (1996) analyzed 7 exons for mutations in the EDNRB gene in 41 isolated patients with HSCR. Two novel mutations were detected (131244.0003 and 131244.0004). Both patients with the novel mutations were heterozygotes. No information was provided on the families of these 2 cases, but the presumption was that they represented new mutations. Amiel et al. (1996) reported 3 missense mutations in the EDNRB gene in heterozygous state in sporadic cases of HSCR. Chakravarti (1996) tabulated 12 mutations in the EDNRB gene identified in cases of Hirschsprung disease up to that time. </p><p>Among 31 isolated cases of Hirschsprung disease in non-inbred populations in Japan, Tanaka et al. (1998) identified 3 new mutations in the EDNRB gene: 2 transversions, A to T and C to A at nucleotides 311 (N104I) and 1170 (S390R), respectively, and a T-to-C transition at nucleotide 325 (C109R). In vitro functional expression studies in Chinese hamster ovary cells revealed that N104I receptors showed almost the same binding affinities and functional properties as the wildtype and might represent a polymorphism. On the other hand, although S390R did not change the binding affinities, it caused decreases in the ligand-induced increment of intracellular calcium and in the inhibition of adenylyl cyclase activity, showing the impairment of the intracellular signaling. C109R receptors were proved to be localized near the nuclei as an unusual 44-kD protein with an extremely low affinity to endothelin-1 and not to be translocated into the plasma membrane. </p><p>Chakravarti (1996) estimated that RET (164761) mutations account for approximately 50% of HSCR cases and EDNRB mutations account for approximately 5%. Short-segment HSCR occurs in about 25% of RET-caused cases and in more than 95% of EDNRB-related cases. Whereas homozygosity for the EDNRB gene can cause deafness and pigmentary anomalies in addition to HSCR (e.g., 131244.0002), the homozygous phenotype for RET has not been observed. </p><p>Carrasquillo et al. (2002) noted that although 8 genes with mutations that can be associated with Hirschsprung disease had been identified, mutations at individual loci are neither necessary nor sufficient to cause clinical disease. They conducted a genomewide association study in 43 Mennonite family trios (parents and affected child) using 2,083 microsatellites and SNPs and a new multipoint linkage disequilibrium method that searched for association arising from common ancestry. They identified susceptibility loci at 10q11, 13q22, and 16q23 (HSCR8; 608462); they showed that the gene at 13q22 is EDNRB and the gene at 10q11 is RET. Statistically significant joint transmission of RET and EDNRB alleles in affected individuals and noncomplementation of aganglionosis in mouse intercrosses between Ret-null and the Ednrb hypomorphic piebald allele were suggestive of epistasis between EDNRB and RET. The findings suggested that genetic interaction between mutations in RET and EDNRB is an underlying mechanism for this complex disorder. </p><p>Sanchez-Mejias et al. (2010) screened the EDN3 (131242) and EDNRB genes in 196 patients with Hirschsprung disease from Spain using high performance liquid chromatography. They found 25 sequence variants in the EDNRB gene; 17 of these were novel. Sanchez-Mejias et al. (2010) screened an additional exon in the 5-prime direction from exon 1 of EDNRB, never previously analyzed in the context of HSCR. Inclusion of this additional exon results in a transcript variant, termed EDNRB-delta-3, with 89 additional amino acids at the N-terminal region of the protein relative to conventional EDNRB. Sanchez-Mejias et al. (2010) detected 3 sequence variants at the 5-prime untranslated region of this additional exon. The most striking finding was the detection of a coding mutation, lys15-to-ter (131244.0009), in a sporadic Hirschsprung disease patient. </p><p><strong><em>Waardenburg Syndrome Type 4A</em></strong></p><p>
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Puffenberger et al. (1994) found that some Mennonites had HSCR associated with nonenteric phenotypes, including bicolored irides (6.3%), hypopigmentation (2.5%), sensorineural hearing loss (5.1%), and white forelock (7.6%), reminiscent of the Shah-Waardenburg syndrome (WS4A; 277580). Puffenberger et al. (1994) suggested that these nonenteric features represented pleiotropic effects of the W276C mutation. They pointed out that the mouse piebald mutation 's' demonstrates white coat spotting as the only phenotypic trait, whereas the piebald-lethal mouse 's(l)' has megacolon in addition to white coat color (Lane, 1966). Hosoda et al. (1994) found that targeted and natural ('piebald-lethal') mutations of the Ednrb mouse result in megacolon associated with spotted coat color. </p><p><strong><em>ABCD Syndrome</em></strong></p><p>
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In a child with ABCD syndrome (600501) reported by Gross et al. (1995), Verheij et al. (2002) identified a homozygous nonsense mutation in the EDNRB gene (131244.0008). Verheij et al. (2002) concluded that the ABCD syndrome is not a separate entity, but rather an expression of Shah-Waardenburg syndrome (WS4). </p>
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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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<p>The autosomal recessive 'spotting lethal' (sl) mutation in the rat is characterized by absence of intramural ganglion cells in the entire colon and distal small bowel, thus resembling human Hirschsprung disease. Ceccherini et al. (1995) excluded linkage of sl with 2 candidate genes, RET protooncogene (RET; 164761) and endothelin-3; however, a highly significant lod score (Z = 47.05 at theta = 0.0) was found between EDNRB and the sl phenotype. The exon-intron structure of the rat gene was reconstructed and each exon of the sl rat was screened for mutations. A 301-bp interstitial deletion, encompassing the distal half of the first coding exon (exon 2) and the proximal part of the adjacent intron, was demonstrated. This deletion resulted in 2 transcriptional products, 270 and 238 bp shorter than wildtype cDNA. Gariepy et al. (1996) showed that the deletion perfectly cosegregates with the sl phenotype. The deletion leads to production of an aberrantly spliced EDNRB mRNA that lacks the coding sequence for the first and second putative transmembrane domains of the G protein-coupled receptor. Radioligand binding assays revealed undetectable levels of functional EDNRB in tissues from homozygous sl/sl rats. Thus, the authors concluded that EDNRB plays an essential role in the normal development of 2 neural crest-derived cell lineages, epidermal melanocytes and enteric neurons, in 3 mammalian species--humans, mice, and rats. They stated that rats lacking EDNRB may prove valuable in studies of adult physiology in health and diseases, if the sl rat can be rescued from the lethal megacolon phenotype. </p><p>Gariepy et al. (1998) demonstrated that during normal rat development the EDNRB mRNA expression pattern is consistent with expression by enteric nervous system (ENS) precursors throughout gut colonization. They used the human dopamine-beta-hydroxylase (DBH; 223360) promoter to direct transgenic expression of EDNRB to colonizing ENS precursors in the sl/sl rat. The DBH-EDNRB transgene compensated for deficient endogenous EDNRB in these rats and prevented the development of congenital intestinal aganglionosis. The transgene had no effect on coat color spotting, indicating the critical time for EDNRB expression in ENS development begins after separation of the melanocyte lineage from the ENS lineage and a common precursor. The transgene dosage affected both the incidence and severity of the congenital intestinal defect, suggesting dosage-dependent events downstream of EDNRB activation in ENS development. </p><p>Shin et al. (1997) attempted to identify the important domains for EDNRB function by studying 4 recessive juvenile lethal alleles in the mouse Ednrb gene created either by radiation or chemical mutagens. Molecular defects were identified in 3; in 1 mutation, which is associated with normal levels of Ednrb mRNA in adult brain, the mutation appeared to affect important regulatory elements that mediate the expression of the gene during development. </p><p>Lethal white foal syndrome (LWFS) is a congenital anomaly of horses resembling Hirschsprung disease characterized by a white coat color and aganglionosis of the bowel. To investigate the molecular basis of LWFS, Yang et al. (1998) demonstrated that a full-length cDNA for horse EDNRB contains a 1,329-bp open reading frame that encoded 443 amino acid residues. The predicted amino acid sequence was 89%, 91%, and 85% identical to human, bovine, and mouse/rat EDNRB sequences, respectively, but only 55% identical to the human, bovine, and rat EDNRA sequences. When homozygous, a dinucleotide mutation, TC-to-AG, which changed isoleucine to lysine in the predicted first transmembrane domain of the EDNRB protein, was found as the basis of LWFS; the heterozygous state resulted in the 'overo' phenotype. The dinucleotide mutation involved nucleotides 353 and 354. It had previously been known that LWFS is produced most often by mating horses with the overo color pattern. One mutant allele produces the coat color change but the presence of at least 1 normal allele appears to protect against the development of aganglionosis. </p><p>Metallinos et al. (1998) also showed that an ile118-to-lys missense mutation in EDNRB is responsible for lethal white foal syndrome. Breedings between particular spotted horses, generally described as frame overo, produce some foals that, in contrast to their parents, are all white or nearly all white and die shortly after birth of severe intestinal blockage. These foals have aganglionosis characterized by a lack of submucosal and myenteric ganglia from the distal small intestine to the large intestine, similar to human Hirschsprung disease. Metallinos et al. (1998) found that lethal white foal syndrome occurred in homozygotes; heterozygotes showed the frame overo pattern. Horses with tobiano markings included some carriers, indicating that tobiano is epistatic to frame overo. In addition, some horses identified as carriers had no recognized overo coat pattern phenotype, demonstrating the incomplete penetrance of the mutation. Santschi et al. (1998) likewise studied the ile118-to-lys change in the overo lethal white syndrome in foals born to American Paint Horse parents of the overo coat pattern lineage. </p><p>To determine when EDNRB signaling is required during embryogenesis, Shin et al. (1999) exploited the tetracycline-inducible system to generate strains of mice that expressed Ednrb at different stages of embryogenesis. Shin et al. (1999) determined that Ednrb is required during a restricted period of neural crest development between embryonic days 10 and 12.5. Shin et al. (1999) concluded that EDNRB is required for the migration of both melanoblasts and enteric neuroblasts. </p><p>The role of the endothelin-B receptor in vascular homeostasis is controversial because the receptor has both pressor and depressor effects in vivo. Spotting lethal rats carry a naturally occurring deletion in the endothelin-B receptor gene that completely abrogates functional receptor expression. Rats homozygous for this mutation die shortly after birth due to congenital distal intestinal aganglionosis. Genetic rescue of homozygous rats from this developmental defect using a dopamine hydroxylase-EDNRB transgene resulted in ETB-deficient adult rats Gariepy et al. (2000). On a sodium-deficient diet, the rats exhibited a normal arterial blood pressure, but on a high-sodium diet the homozygous sl rats became severely hypertensive. Normal pressure was restored in the salt-fed rats when the epithelial sodium channel was blocked with amiloride. Gariepy et al. (2000) concluded that the rescued sl/sl rats are a novel single-locus genetic model of severe salt-sensitive hypertension. The results suggested that these rats are hypertensive because they lack the normal tonic inhibition of the renal epithelial sodium channel. </p><p>Matsushima et al. (2002) described a novel mutant mouse with a mutation in the Ednrb gene and proposed the mouse as an animal model of Waardenburg syndrome 4 (WS4; see 277580), or Waardenburg-Shah syndrome, which combines Hirschsprung disease with features of Waardenburg syndrome. These mutants had a mixed genetic background and extensive white spotting. They died between 2 and 7 weeks after birth owing to megacolon; their colon distal to the megacolon lacked Auerbach plexus cells. These mutants did not respond to sound, and the stria vascularis of their cochleae lacked intermediate cells, i.e., neural crest-derived melanocytes. The inheritance was autosomal recessive as in human WS4. Breeding analysis revealed that WS4 mice are allelic with piebald-lethal and JF1 mice, which are also mutated in the Ednrb gene. Mutation analysis showed that the Ednrb gene lacked 318 nucleotides encoding transmembrane domains owing to deletion of exons 2 and 3. Interaction between endothelin-3 (131242) and its receptor is required for normal differentiation and development of melanocytes and Auerbach plexus cells. </p><p>Carpenter et al. (2003) studied pulmonary edema formation in EDNRB-deficient rats. In normoxia, EDNRB -/- rats had significantly more lung vascular leak than heterozygotes or controls. Hypoxia increased vascular leak regardless of genotype, and hypoxic EDNRB-deficient rats leaked more than hypoxic controls. EDNRB-deficient rats had higher lung endothelin levels in both normoxia and hypoxia. Lung hypoxia-inducible factor-1-alpha (HIF1A; 603348) and vascular endothelial growth factor (VEGF; 192240) levels were greater in the EDNRB-deficient rats in both normoxia and hypoxia, and both levels were reduced by EDNRA antagonism. Both EDNRA blockade and VEGF antagonism reduced vascular leak in hypoxic EDNRB-deficient rats. Carpenter et al. (2003) concluded that EDNRB-deficient rats display an exaggerated lung vascular protein leak in normoxia, that hypoxia exacerbates that leak, and that this effect is in part attributable to an endothelin-mediated increase in lung VEGF content. </p><p>Migration of the precursors of the enteric nervous system (ENS) into the colon requires expression of the EDNRB gene at a defined time. In studies in mice, Zhu et al. (2004) found a conserved spatiotemporal ENS enhancer of Ednrb. This 1-kb enhancer was activated as the ENS precursors approached the colon, and partial deletion of the enhancer at the endogenous Ednrb locus resulted in pigmented mice that died postnatally from megacolon. In the Ednrb ENS enhancer, they identified binding sites for Sox10 (602229), an SRY-related transcription factor associated with Hirschsprung disease, and mutational analyses of these sites suggested that SOX10 may have multiple roles in regulating EDNRB in the ENS. </p><p>Cantrell et al. (2004) tested for association between genes in the endothelin signaling pathway and severity of aganglionosis in an extended pedigree of B6C3FeLe.Sox10(Dom) mice. Single-locus association analysis identified interaction between EdnrB and Sox10. Additional analysis of F2 intercross progeny confirmed a highly significant effect of EdnrB alleles on the Sox10(Dom/+) phenotype. The presence of C57BL/6J alleles at EdnrB was associated with increased penetrance and more severe aganglionosis in Sox10(Dom) mutants. Crosses between EdnrB and Sox10 mutants corroborated this gene interaction, with double-mutant progeny exhibiting significantly more severe aganglionosis. The background strain of the EdnrB mutant further influenced the phenotype of Sox10/EdnrB double-mutant progeny, implying the action of additional modifiers on this phenotype. </p><p>In adult transgenic mice with conditional cardiac-restricted ET1 overexpression, Yang et al. (2004) observed nuclear factor kappa-B (see 164011) translocation, cytokine expression, inflammation and hypertrophy, resulting in dilated cardiomyopathy, congestive heart failure, and death as early as 5 weeks after transgene induction. Significant prolongation of survival was observed with a combined EDNRA/EDNRB antagonist but not with an EDNRA-selective antagonist, consistent with an important role for EDNRB in this model. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>9 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 HIRSCHSPRUNG DISEASE, SUSCEPTIBILITY TO, 2</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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WAARDENBURG SYNDROME, TYPE 4A, 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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EDNRB, TRP276CYS
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<br />
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SNP: rs104894387,
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gnomAD: rs104894387,
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ClinVar: RCV000018112, RCV000018113, RCV003236768
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</span>
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<span class="mim-text-font">
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<p>In an extensive Mennonite kindred with many cases of Hirschsprung disease (600155), Puffenberger et al. (1994) found a G-to-T missense mutation in exon 4 of the EDNRB gene, resulting in substitution of the highly conserved tryptophan-276 residue with a cysteine residue (W276C) in the fifth transmembrane helix of the G protein-coupled receptor. The mutant W276C receptor exhibited a partial impairment of ligand-induced Ca(2+) transient levels in transfected cells. HSCR was observed in 74% of W276C homozygotes and 21% of W276C heterozygotes. In addition to HSCR, nonenteric manifestations suggestive of Waardenburg-Shah syndrome (WS4A; 277580) were observed in individuals with the mutation: bicolored irides in 6.3%, hypopigmentation in 2.5%, sensorineural hearing loss in 5.1%, and white forelock in 7.6%. </p>
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</span>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 WAARDENBURG SYNDROME, TYPE 4A</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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EDNRB, ALA183GLY
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<br />
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SNP: rs104894388,
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ClinVar: RCV000018114
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<div>
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<span class="mim-text-font">
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<p>In 2 girls born to consanguineous Tunisian parents, Attie et al. (1995) described features of both Waardenburg syndrome and Hirschsprung disease (277580). They excluded RET and PAX3 (606597) as candidate genes by linkage analysis but found a homozygous missense mutation in exon 2 of the EDNRB gene. Using microsatellite DNA markers flanking the EDNRB gene, they showed that the 2 affected sibs were geno-identical and homozygous at these loci, whereas the 2 unaffected brothers shared no more than 1 allele with their affected sisters. The affected sisters showed an abnormal SSCP pattern in exon 2 and direct DNA sequencing revealed a C-to-G transversion at the second nucleotide of codon 183, predicted to result in the replacement of an alanine by a glycine (A183G) in the third transmembrane domain of EDNRB. The parents and 1 healthy brother who was studied were heterozygous for the A183G mutation. Neither affected sister had dystopia canthorum. However, both had deafness, white forelock, and heterochromia iridis, as well as Hirschsprung disease. </p>
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</span>
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</div>
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<div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 HIRSCHSPRUNG DISEASE, SUSCEPTIBILITY TO, 2</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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EDNRB, TRP275TER
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<br />
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SNP: rs104894389,
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gnomAD: rs104894389,
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ClinVar: RCV000018115
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In an isolated case of Hirschsprung disease (600155), Kusafuka et al. (1996) identified a G-to-A transition at nucleotide 824 of the EDNRB gene. The patient was heterozygous and apparently this represented a new mutation. Aganglionosis was confined to the rectosigmoid colon and there was no associated abnormality. The mutation converted a TGG (trp) codon to a stop codon at residue 275. </p>
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</span>
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</div>
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<div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 HIRSCHSPRUNG DISEASE, SUSCEPTIBILITY TO, 2</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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EDNRB, 1-BP INS, 878T
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<br />
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SNP: rs769735757,
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gnomAD: rs769735757,
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ClinVar: RCV000018116
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In an isolated case of Hirschsprung disease (600155), Kusafuka et al. (1996) found insertion of a T after nucleotide 878 in the EDNRB gene. The patient was heterozygous and presumably represented a new mutation, although no family studies were performed. The mutation caused a frameshift with early termination of translation at nucleotide 894. The aganglionosis was confined to the descending colon, and there were no associated abnormalities. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0005 HIRSCHSPRUNG DISEASE, SUSCEPTIBILITY TO, 2</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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EDNRB, GLY57SER
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<br />
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SNP: rs1801710,
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gnomAD: rs1801710,
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ClinVar: RCV000018117, RCV000216329, RCV000224294
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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>Svensson et al. (1998) described a family with Hirschsprung disease (600155) with missense mutations in both the RET gene (arg982 to cys; 164761.0036) and the EDNRB gene, gly57 to ser (G57S). In this family, 3 of 5 members had both mutations, but only 1, a boy, had the Hirschsprung disease phenotype. Hofstra et al. (1997) found the G57S mutation in 3 of 40 HSCR patients, but also in 4 of 180 control chromosomes. With the controls studied by Svensson et al. (1998), the figure comes to 4 of 410 control chromosomes. In the family of Svensson et al. (1998) the mother and a daughter carried both mutations; the G57S mutation was present in homozygous state in the daughter who had inherited the mutation from each parent. The fact that family members are healthy carriers of G57S in hetero- or homozygous form suggested a sex-dependent gene-dosage effect, comparable to that observed by Puffenberger et al. (1994) in a Mennonite kindred with the trp276-to-cys mutation (131244.0001), in which there were heterozygous as well as homozygous healthy carriers of the founder mutation. The penetrance was higher in males, however. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0006 HIRSCHSPRUNG DISEASE, SUSCEPTIBILITY TO, 2</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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EDNRB, SER305ASN
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<br />
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SNP: rs5352,
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gnomAD: rs5352,
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ClinVar: RCV000018118, RCV000222856, RCV000626404, RCV000659497, RCV000954472, RCV001258252
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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 patient with Hirschsprung disease (600155), Auricchio et al. (1999) found double heterozygosity for a silent mutation, I647I, of the RET gene (164761.0037), inherited from the unaffected mother, and an EDNRB missense mutation, S305N, transmitted by the healthy father. In 2 different patients they demonstrated both in vivo and in vitro that the silent RET mutation can interfere with correct transcription, possibly leading to a reduced level of the RET protein. The coexistence in the same patient of 2 functionally significant EDNRB and RET mutations suggested a direct genetic interaction between these 2 distinct transmembrane receptors in polygenic HSCR disease. </p><p>Lek et al. (2016) questioned the validity of this variant as a susceptibility allele because it has a high global allele frequency (0.0089) in the ExAC database. </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>.0007 WAARDENBURG SYNDROME, TYPE 4A</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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EDNRB, ARG253TER
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<br />
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SNP: rs104894390,
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gnomAD: rs104894390,
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ClinVar: RCV000018119, RCV001851902
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a family with Waardenburg-Shah syndrome (277580), Syrris et al. (1999) identified a heterozygous C-to-T transition in exon 3 of the EDNRB gene, resulting in an arg253-to-ter (R253X) substitution resulting in premature termination. The mutation was not observed in over 50 unrelated controls. The data confirmed the role of EDNRB in the cause of Waardenburg-Shah disease and demonstrated that in this disorder there is a lack of correlation between phenotype and genotype and a variable expression of disease even within the same family. The family studied by Syrris et al. (1999) was of Afro-Caribbean origin and had a history of sensorineural deafness, heterochromia iridis, and Hirschsprung disease. Synophrys, hair or skin hypopigmentation, and dystopia canthorum were absent in this family. </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>.0008 ABCD SYNDROME (1 family)</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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EDNRB, ARG201TER
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<br />
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SNP: rs104894391,
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gnomAD: rs104894391,
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|
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ClinVar: RCV000018120, RCV000659496, RCV001092078
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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 the fifth child affected with ABCD syndrome (600501) in a consanguineous Kurdish family, previously described by Gross et al. (1995), Verheij et al. (2002) identified a homozygous C-to-T transition in exon 3 of the EDNRB gene, resulting in the substitution of a stop codon for an arginine residue (R201X). The affected female infant presented with bilateral deafness, albinism, a black lock at the right temporooccipital region, and spots of retinal depigmentation. She also had a severe defect of intestinal innervation from which she died at 5 weeks of age. Verheij et al. (2002) suggested that ABCD syndrome is not a separate entity, but an expression of Shah-Waardenburg syndrome (277580). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0009 HIRSCHSPRUNG DISEASE, SUSCEPTIBILITY TO, 2</strong>
|
|
</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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EDNRB, LYS15TER
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<br />
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SNP: rs267606780,
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|
|
ClinVar: RCV000018121
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|
|
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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 Spanish male patient with sporadic Hirschsprung disease (600155), Sanchez-Mejias et al. (2010) identified an A-to-T transversion at nucleotide 43 of the EDNRB gene, resulting in a lysine-to-termination substitution in codon 15 (K15X). This mutation was not identified in any other family members other than the father from whom the child inherited it. The father did not have Hirschsprung disease. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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|
<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
|
|
Amiel, J., Attie, T., Jan, D., Pelet, A., Edery, P., Bidaud, C., Lacombe, D., Tam, P., Simeoni, J., Flori, E., Nihoul-Fekete, C., Munnich, A., Lyonnet, S.
|
|
<strong>Heterozygous endothelin receptor B (EDNRB) mutations in isolated Hirschsprung disease.</strong>
|
|
Hum. Molec. Genet. 5: 355-357, 1996.
|
|
|
|
|
|
[PubMed: 8852660]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/5.3.355]
|
|
|
|
|
|
</p>
|
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</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Arai, H., Nakao, K., Takaya, K., Hosoda, K., Ogawa, Y., Nakanishi, S., Imura, H.
|
|
<strong>The human endothelin-B receptor gene: structural organization and chromosomal assignment.</strong>
|
|
J. Biol. Chem. 268: 3463-3470, 1993.
|
|
|
|
|
|
[PubMed: 8429023]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Attie, T., Till, M., Pelet, A., Amiel, J., Edery, P., Boutrand, L., Munnich, A., Lyonnet, S.
|
|
<strong>Mutation of the endothelin-receptor B gene in Waardenburg-Hirschsprung disease.</strong>
|
|
Hum. Molec. Genet. 4: 2407-2409, 1995.
|
|
|
|
|
|
[PubMed: 8634719]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/4.12.2407]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Auricchio, A., Griseri, P., Carpentieri, M. L., Betsos, N., Staiano, A., Tozzi, A., Priolo, M., Thompson, H., Bocciardi, R., Romeo, G., Ballabio, A., Ceccherini, I.
|
|
<strong>Double heterozygosity for a RET substitution inferring with splicing and an EDNRB missense mutation in Hirschsprung disease. (Letter)</strong>
|
|
Am. J. Hum. Genet. 64: 1216-1221, 1999.
|
|
|
|
|
|
[PubMed: 10090908]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/302329]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bourgeois, C., Robert, B., Rebourcet, R., Mondon, F., Mignot, T.-M., Duc-Goiran, P., Ferre, F.
|
|
<strong>Endothelin-1 and ET(A) receptor expression in vascular smooth muscle cells from human placenta: a new ET(A) receptor messenger ribonucleic acid is generated by alternative splicing of exon 3.</strong>
|
|
J. Clin. Endocr. Metab. 82: 3116-3123, 1997.
|
|
|
|
|
|
[PubMed: 9284755]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.82.9.4209]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Buckanovich, R. J., Facciabene, A., Kim, S., Benencia, F., Sasaroli, D., Balint, K., Katsaros, D., O'Brien-Jenkins, A., Gimotty, P. A., Coukos, G.
|
|
<strong>Endothelin B receptor mediates the endothelial barrier to T cell homing to tumors and disables immune therapy.</strong>
|
|
Nature Med. 14: 28-36, 2008.
|
|
|
|
|
|
[PubMed: 18157142]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nm1699]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cantrell, V. A., Owens, S. E., Chandler, R. L., Airey, D. C., Bradley, K. M., Smith, J. R., Southard-Smith, E. M.
|
|
<strong>Interactions between Sox10 and EdnrB modulate penetrance and severity of aganglionosis in the Sox10(Dom) mouse model of Hirschsprung disease.</strong>
|
|
Hum. Molec. Genet. 13: 2289-2301, 2004. Note: Erratum: Hum. Molec. Genet. 13: 3241 only, 2004.
|
|
|
|
|
|
[PubMed: 15294878]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddh243]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Carpenter, T., Schomberg, S., Steudel, W., Ozimek, J., Colvin, K., Stenmark, K., Ivy, D. D.
|
|
<strong>Endothelin B receptor deficiency predisposes to pulmonary edema formation via increased lung vascular endothelial cell growth factor expression.</strong>
|
|
Circ. Res. 93: 456-463, 2003.
|
|
|
|
|
|
[PubMed: 12919946]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1161/01.RES.0000090994.15442.42]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Carrasquillo, M. M., McCallion, A. S., Puffenberger, E. G., Kashuk, C. S., Nouri, N., Chakravarti, A.
|
|
<strong>Genome-wide association study and mouse model identify interaction between RET and EDNRB pathways in Hirschsprung disease.</strong>
|
|
Nature Genet. 32: 237-244, 2002.
|
|
|
|
|
|
[PubMed: 12355085]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng998]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ceccherini, I., Zhang, A. L., Matera, I., Yang, G., Devoto, M., Romeo, G., Cass, D. T.
|
|
<strong>Interstitial deletion of the endothelin-B receptor gene in the spotting lethal (sl) rat.</strong>
|
|
Hum. Molec. Genet. 4: 2089-2096, 1995.
|
|
|
|
|
|
[PubMed: 8589685]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/4.11.2089]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chakravarti, A.
|
|
<strong>Endothelin receptor-mediated signaling in Hirschsprung disease.</strong>
|
|
Hum. Molec. Genet. 5: 303-307, 1996.
|
|
|
|
|
|
[PubMed: 8852653]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Elshourbagy, N. A., Adamou, J. E., Gagnon. A. W., Wu, H.-L., Pullen, M., Nambi, P.
|
|
<strong>Molecular characterization of a novel human endothelin receptor splice variant.</strong>
|
|
J. Biol. Chem. 271: 25300-25307, 1996.
|
|
|
|
|
|
[PubMed: 8810293]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.271.41.25300]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gariepy, C. E., Cass, D. T., Yanagisawa, M.
|
|
<strong>Null mutation of endothelin receptor type B gene in spotting lethal rats causes aganglionic megacolon and white coat color.</strong>
|
|
Proc. Nat. Acad. Sci. 93: 867-872, 1996.
|
|
|
|
|
|
[PubMed: 8570650]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.93.2.867]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gariepy, C. E., Ohuchi, T., Williams, S. C., Richardson, J. A., Yanagisawa, M.
|
|
<strong>Salt-sensitive hypertension in endothelin-B receptor-deficient rats.</strong>
|
|
J. Clin. Invest. 105: 925-933, 2000.
|
|
|
|
|
|
[PubMed: 10749572]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI8609]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gariepy, C. E., Williams, S. C., Richardson, J. A., Hammer, R. E., Yanagisawa, M.
|
|
<strong>Transgenic expression of the endothelin-B receptor prevents congenital intestinal aganglionosis in a rat model of Hirschsprung disease.</strong>
|
|
J. Clin. Invest. 102: 1092-1101, 1998.
|
|
|
|
|
|
[PubMed: 9739043]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI3702]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gross, A., Kunze, J., Maier, R. F., Stoltenburg-Didinger, G., Grimmer, I., Obladen, M.
|
|
<strong>Autosomal-recessive neural crest syndrome with albinism, black lock, cell migration disorder of the neurocytes of the gut, and deafness: ABCD syndrome.</strong>
|
|
Am. J. Med. Genet. 56: 322-326, 1995.
|
|
|
|
|
|
[PubMed: 7778600]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320560322]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hofstra, R. M. W., Osinga, J., Buys, C. H. C. M.
|
|
<strong>Mutations in Hirschsprung disease: when does a mutation contribute to the phenotype?</strong>
|
|
Europ. J. Hum. Genet. 5: 180-185, 1997.
|
|
|
|
|
|
[PubMed: 9359036]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hosoda, K., Hammer, R. E., Richardson, J. A., Baynash, A. G., Cheung, J. C., Giaid, A., Yanagisawa, M.
|
|
<strong>Targeted and natural (piebald-lethal) mutations of endothelin-B receptor gene produce megacolon associated with spotted coat color in mice.</strong>
|
|
Cell 79: 1267-1276, 1994.
|
|
|
|
|
|
[PubMed: 8001159]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0092-8674(94)90017-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Iwashita, T., Kruger, G. M., Pardal, R., Kiel, M. J., Morrison, S. J.
|
|
<strong>Hirschsprung disease is linked to defects in neural crest stem cell function.</strong>
|
|
Science 301: 972-976, 2003.
|
|
|
|
|
|
[PubMed: 12920301]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1085649]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Khodorova, A., Navarro, B., Jouaville, L. S., Murphy, J.-E., Rice, F. I., Mazurkiewicz, J. E., Long-Woodward, D., Stoffel, M., Strichartz, G. R., Yukhananov, R., Davar, G.
|
|
<strong>Endothelin-B receptor activation triggers an endogenous analgesic cascade at sites of peripheral injury.</strong>
|
|
Nature Med. 9: 1055-1061, 2003.
|
|
|
|
|
|
[PubMed: 12847519]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nm885]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kusafuka, T., Wang, Y., Puri, P.
|
|
<strong>Novel mutations of the endothelin-B receptor gene in isolated patients with Hirschsprung's disease.</strong>
|
|
Hum. Molec. Genet. 5: 347-349, 1996.
|
|
|
|
|
|
[PubMed: 8852658]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/5.3.347]
|
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</p>
|
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</li>
|
|
|
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<li>
|
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<p class="mim-text-font">
|
|
Lane, P. W.
|
|
<strong>Association of megacolon with two recessive spotting genes in the mouse.</strong>
|
|
J. Hered. 57: 29-31, 1966.
|
|
|
|
|
|
[PubMed: 5917257]
|
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|
|
|
|
[Full Text: https://doi.org/10.1093/oxfordjournals.jhered.a107457]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Lek, M., Karczewski, K. J., Minikel, E. V., Samocha, K. E., Banks, E., Fennell, T., O'Donnell-Luria, A. H., Ware, J. S., Hill, A. J., Cummings, B. B., Tukiainen, T., Birnbaum, D. P., and 68 others.
|
|
<strong>Analysis of protein-coding genetic variation in 60,706 humans.</strong>
|
|
Nature 536: 285-291, 2016.
|
|
|
|
|
|
[PubMed: 27535533]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature19057]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Maggi, M., Barni, T., Fantoni, G., Mancina, R., Pupilli, C., Luconi, M., Crescioli, C., Serio, M., Vannelli, G. B.
|
|
<strong>Expression and biological effects of endothelin-1 in human gonadotropin-releasing hormone-secreting neurons.</strong>
|
|
J. Clin. Endocr. Metab. 85: 1658-1665, 2000.
|
|
|
|
|
|
[PubMed: 10770212]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.85.4.6565]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Matsushima, Y., Shinkai, Y., Kobayashi, Y., Sakamoto, M., Kunieda, T., Tachibana, M.
|
|
<strong>A mouse model of Waardenburg syndrome type 4 with a new spontaneous mutation of the endothelin-B receptor gene.</strong>
|
|
Mammalian Genome 13: 30-35, 2002.
|
|
|
|
|
|
[PubMed: 11773966]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00335-001-3038-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Metallinos, D. L., Bowling, A. T., Rine, J.
|
|
<strong>A missense mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome: an equine version of Hirschsprung disease.</strong>
|
|
Mammalian Genome 9: 426-431, 1998.
|
|
|
|
|
|
[PubMed: 9585428]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s003359900790]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nakamuta, M., Takayanagi, R., Sakai, Y., Sakamoto, S., Hagiwara, H., Mizuno, T., Saito, Y., Hirose, S., Yamamoto, M., Nawata, H.
|
|
<strong>Cloning and sequence analysis of a cDNA encoding human non-selective type of endothelin receptor.</strong>
|
|
Biochem. Biophys. Res. Commun. 177: 34-39, 1991.
|
|
|
|
|
|
[PubMed: 1710450]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0006-291x(91)91944-8]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ogawa, Y., Nakao, K., Arai, H., Nakagawa, O., Hosoda, K., Suga, S., Nakanishi, S., Imura, H.
|
|
<strong>Molecular cloning of a non-isopeptide-selective human endothelin receptor.</strong>
|
|
Biochem. Biophys. Res. Commun. 178: 248-255, 1991.
|
|
|
|
|
|
[PubMed: 1648908]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0006-291x(91)91806-n]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Okafor, M. C., Delamere, N. A.
|
|
<strong>The inhibitory influence of endothelin on active sodium-potassium transport in porcine lens.</strong>
|
|
Invest. Ophthal. Vis. Sci. 42: 1018-1023, 2001.
|
|
|
|
|
|
[PubMed: 11274080]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pao, M. M., Tsutsumi, M., Liang, G., Uzvolgyi, E., Gonzales, F. A., Jones, P. A.
|
|
<strong>The endothelin receptor B (EDNRB) promoter displays heterogeneous, site specific methylation patterns in normal and tumor cells.</strong>
|
|
Hum. Molec. Genet. 10: 903-910, 2001.
|
|
|
|
|
|
[PubMed: 11309363]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/10.9.903]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Puffenberger, E. G., Hosoda, K., Washington, S. S., Nakao, K., deWit, D., Yanagisawa, M., Chakravarti, A.
|
|
<strong>A missense mutation of the endothelin-B receptor gene in multigenic Hirschsprung's disease.</strong>
|
|
Cell 79: 1257-1266, 1994.
|
|
|
|
|
|
[PubMed: 8001158]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0092-8674(94)90016-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sanchez-Mejias, A., Fernandez, R. M., Lopez-Alonso, M., Antinolo, G., Borrego, S.
|
|
<strong>New roles of EDNRB and EDN3 in the pathogenesis of Hirschsprung disease.</strong>
|
|
Genet. Med. 12: 39-43, 2010.
|
|
|
|
|
|
[PubMed: 20009762]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1097/GIM.0b013e3181c371b0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Santschi, E. M., Purdy, A. K., Valberg, S. J., Vrotsos, P. D., Kaese, H., Mickelson, J. R.
|
|
<strong>Endothelin receptor B polymorphism associated with lethal white foal syndrome in horses.</strong>
|
|
Mammalian Genome 9: 306-309, 1998.
|
|
|
|
|
|
[PubMed: 9530628]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s003359900754]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shihoya, W., Nishizawa, T., Okuta, A., Tani, K., Dohmae, N., Fujiyoshi, Y., Nureki, O., Doi, T.
|
|
<strong>Activation mechanism of endothelin ET(B) receptor by endothelin-1.</strong>
|
|
Nature 537: 363-368, 2016.
|
|
|
|
|
|
[PubMed: 27595334]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature19319]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shin, M. K., Levorse, J. M., Ingram, R. S., Tilghman, S. M.
|
|
<strong>The temporal requirement for endothelin receptor-B signalling during neural crest development.</strong>
|
|
Nature 402: 496-501, 1999.
|
|
|
|
|
|
[PubMed: 10591209]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/990040]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shin, M. K., Russell, L. B., Tilghman, S. M.
|
|
<strong>Molecular characterization of four induced alleles at the Ednrb locus.</strong>
|
|
Proc. Nat. Acad. Sci. 94: 13105-13110, 1997.
|
|
|
|
|
|
[PubMed: 9371807]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.94.24.13105]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Svensson, P.-J., Anvret, M., Molander, M.-L., Nordenskjold, A.
|
|
<strong>Phenotypic variation in a family with mutations in two Hirschsprung-related genes (RET and endothelin receptor B).</strong>
|
|
Hum. Genet. 103: 145-148, 1998.
|
|
|
|
|
|
[PubMed: 9760196]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s004390050797]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Syrris, P., Carter, N. D., Patton, M. A.
|
|
<strong>Novel nonsense mutation of the endothelin-B receptor gene in a family with Waardenburg-Hirschsprung disease.</strong>
|
|
Am. J. Med. Genet. 87: 69-71, 1999.
|
|
|
|
|
|
[PubMed: 10528251]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Takayanagi, R., Ohnaka, K., Takasaki, C., Ohashi, M., Nawata, H.
|
|
<strong>Multiple subtypes of endothelin receptors in porcine tissues: characterization by ligand binding, affinity labeling and regional distribution.</strong>
|
|
Regul. Pept. 32: 23-37, 1991.
|
|
|
|
|
|
[PubMed: 1848367]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0167-0115(91)90004-z]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tanaka, H., Moroi, K., Iwai, J., Takahashi, H., Ohnuma, N., Hori, S., Takimoto, M., Nishiyama, M., Masaki, T., Yanagisawa, M., Sekiya, S., Kimura, S.
|
|
<strong>Novel mutations of the endothelin B receptor gene in patients with Hirschsprung's disease and their characterization.</strong>
|
|
J. Biol. Chem. 273: 11378-11383, 1998.
|
|
|
|
|
|
[PubMed: 9556633]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.273.18.11378]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vane, J. R.
|
|
<strong>Endothelins come home to roost.</strong>
|
|
Nature 348: 673, 1990.
|
|
|
|
|
|
[PubMed: 2175394]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/348673a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Verheij, J. B. G. M., Kunze, J., Osinga, J., van Essen, A. J., Hofstra, R. M. W.
|
|
<strong>ABCD syndrome is caused by a homozygous mutation in the EDNRB gene.</strong>
|
|
Am. J. Med. Genet. 108: 223-225, 2002.
|
|
|
|
|
|
[PubMed: 11891690]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.10172]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wang, L., Fortune, B., Cull, G., Dong, J., Cioffi, G. A.
|
|
<strong>Endothelin B receptor in human glaucoma and experimentally induced optic nerve damage.</strong>
|
|
Arch. Ophthal. 124: 717-724, 2006.
|
|
|
|
|
|
[PubMed: 16682595]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archopht.124.5.717]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yang, G. C., Croaker, D., Zhang, A. L., Manglick, P., Cartmill, T., Cass, D.
|
|
<strong>A dinucleotide mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome (LWFS); a horse variant of Hirschsprung disease (HSCR).</strong>
|
|
Hum. Molec. Genet. 7: 1047-1052, 1998.
|
|
|
|
|
|
[PubMed: 9580670]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/7.6.1047]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yang, L. L., Gros, R., Kabir, M. G., Sadi, A., Gotlieb, A. I., Husain, M., Stewart, D. J.
|
|
<strong>Conditional cardiac overexpression of endothelin-1 induces inflammation and dilated cardiomyopathy in mice.</strong>
|
|
Circulation 109: 255-261, 2004.
|
|
|
|
|
|
[PubMed: 14718401]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1161/01.CIR.0000105701.98663.D4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zeidel, M. L., Brady, H. R., Kone, B. C., Gullans, S. R., Brenner, B. M.
|
|
<strong>Endothelin, a peptide inhibitor of Na(+)-K(+)-ATPase in intact renal tubular epithelial cells.</strong>
|
|
Am. J. Physiol. 257: C1101-C1107, 1989.
|
|
|
|
|
|
[PubMed: 2558568]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1152/ajpcell.1989.257.6.C1101]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zhu, L., Lee, H.-O., Jordan, C. S., Cantrell, V. A., Southard-Smith, E. M., Shin, M. K.
|
|
<strong>Spatiotemporal regulation of endothelin receptor-B by SOX10 in neural crest-derived enteric neuron precursors.</strong>
|
|
Nature Genet. 36: 732-737, 2004.
|
|
|
|
|
|
[PubMed: 15170213]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1371]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
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|
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|
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<span class="text-nowrap mim-text-font">
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Contributors:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh - updated : 11/30/2016<br>Ada Hamosh - updated : 09/27/2016<br>Ada Hamosh - updated : 5/27/2010<br>Paul J. Converse - updated : 3/5/2008<br>George E. Tiller - updated : 4/5/2007<br>Jane Kelly - updated : 12/7/2006<br>Marla J. F. O'Neill - updated : 11/11/2005<br>Victor A. McKusick - updated : 7/7/2004<br>Marla J. F. O'Neill - updated : 3/12/2004<br>Ada Hamosh - updated : 8/26/2003<br>Victor A. McKusick - updated : 7/1/2003<br>Victor A. McKusick - updated : 9/25/2002<br>Victor A. McKusick - updated : 5/23/2002<br>Deborah L. Stone - updated : 4/25/2002<br>Jane Kelly - updated : 1/25/2002<br>George E. Tiller - updated : 9/28/2001<br>John A. Phillips, III - updated : 12/1/2000<br>Ada Hamosh - updated : 2/1/2000<br>Victor A. McKusick - updated : 11/23/1999<br>Victor A. McKusick - updated : 4/9/1999<br>Victor A. McKusick - updated : 3/11/1999<br>Victor A. McKusick - updated : 10/29/1998<br>Victor A. McKusick - updated : 10/6/1998<br>Victor A. McKusick - updated : 9/4/1998<br>Victor A. McKusick - updated : 7/30/1998<br>Victor A. McKusick - updated : 6/15/1998<br>Victor A. McKusick - updated : 2/24/1998<br>John A. Phillips, III - updated : 10/6/1997<br>Jennifer P. Macke - updated : 5/20/1997
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Victor A. McKusick : 7/12/1991
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Edit History:
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carol : 09/03/2024<br>carol : 09/24/2022<br>carol : 04/19/2022<br>carol : 12/01/2016<br>carol : 11/30/2016<br>alopez : 09/27/2016<br>carol : 09/18/2013<br>terry : 3/28/2013<br>carol : 6/1/2011<br>wwang : 5/12/2011<br>carol : 7/29/2010<br>alopez : 6/2/2010<br>terry : 5/27/2010<br>ckniffin : 3/15/2010<br>carol : 3/11/2010<br>ckniffin : 3/8/2010<br>mgross : 3/5/2008<br>alopez : 12/5/2007<br>alopez : 4/13/2007<br>terry : 4/5/2007<br>carol : 12/7/2006<br>terry : 12/7/2006<br>wwang : 11/11/2005<br>alopez : 7/9/2004<br>terry : 7/7/2004<br>tkritzer : 3/30/2004<br>ckniffin : 3/16/2004<br>tkritzer : 3/12/2004<br>alopez : 8/29/2003<br>alopez : 8/26/2003<br>terry : 8/26/2003<br>alopez : 7/2/2003<br>terry : 7/1/2003<br>alopez : 9/25/2002<br>alopez : 9/25/2002<br>alopez : 9/25/2002<br>tkritzer : 9/23/2002<br>alopez : 5/28/2002<br>terry : 5/23/2002<br>carol : 4/25/2002<br>terry : 4/25/2002<br>carol : 1/29/2002<br>terry : 1/25/2002<br>carol : 1/8/2002<br>cwells : 10/9/2001<br>cwells : 9/28/2001<br>mgross : 12/1/2000<br>mcapotos : 6/9/2000<br>mcapotos : 6/8/2000<br>alopez : 2/2/2000<br>terry : 2/1/2000<br>carol : 11/29/1999<br>terry : 11/23/1999<br>carol : 4/12/1999<br>terry : 4/9/1999<br>carol : 3/29/1999<br>terry : 3/11/1999<br>psherman : 2/15/1999<br>carol : 1/4/1999<br>carol : 11/2/1998<br>terry : 10/29/1998<br>carol : 10/12/1998<br>terry : 10/6/1998<br>alopez : 9/9/1998<br>carol : 9/4/1998<br>carol : 8/3/1998<br>terry : 7/30/1998<br>carol : 7/8/1998<br>dkim : 7/2/1998<br>alopez : 6/17/1998<br>terry : 6/15/1998<br>alopez : 2/25/1998<br>terry : 2/24/1998<br>jenny : 12/1/1997<br>jenny : 11/17/1997<br>alopez : 8/12/1997<br>alopez : 7/25/1997<br>alopez : 7/25/1997<br>mark : 4/17/1996<br>terry : 4/10/1996<br>mark : 2/9/1996<br>terry : 2/8/1996<br>mark : 1/18/1996<br>terry : 1/16/1996<br>mark : 1/16/1996<br>mark : 1/10/1996<br>terry : 1/26/1995<br>carol : 3/20/1993<br>supermim : 3/16/1992<br>carol : 2/20/1992<br>carol : 9/12/1991
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