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<title>
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Entry
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- *605111 - SPHINGOSINE-1-PHOSPHATE RECEPTOR 2; S1PR2
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- OMIM
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<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
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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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<button type="submit" id="mimEntrySearchSubmit" class="btn btn-default" style="width: 5em;"><span class="glyphicon glyphicon-search"></span></button>
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Advanced Search
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<a href="/search/advanced/entry"> OMIM </a>
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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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<a href="/search/advanced/geneMap"> Gene Map </a>
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<p />
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<div class="row">
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*605111</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 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="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#nomenclature">Nomenclature</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="#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 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/605111">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 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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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000267534;t=ENST00000646641" 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=9294" 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=605111" 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=ENSG00000267534;t=ENST00000646641" 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_004230" 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_004230" 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=605111" 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=05488&isoform_id=05488_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/S1PR2" 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/4090956,30171330,38257367,47479591,119604487,119604488,134244587" 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/O95136" 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=9294" 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=ENSG00000267534;t=ENST00000646641" 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=S1PR2" 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=S1PR2" 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+9294" 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/S1PR2" 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:9294" 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/9294" 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=chr19&hgg_gene=ENST00000646641.1&hgg_start=10221433&hgg_end=10231331&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/genes/HGNC:3169" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=605111[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=605111[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000267534" 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=S1PR2" 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=S1PR2" 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=S1PR2" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=S1PR2&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/PA162402353" 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:3169" 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:99569" 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/S1PR2#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:99569" 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/9294/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=9294" 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-020123-2" 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">
|
|
<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<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:9294" 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=S1PR2&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
|
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</div>
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<div>
|
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<span class="h3">
|
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<span class="mim-font mim-tip-hint" title="Gene description">
|
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<span class="text-danger"><strong>*</strong></span>
|
|
605111
|
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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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|
|
SPHINGOSINE-1-PHOSPHATE RECEPTOR 2; S1PR2
|
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|
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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 />
|
|
</div>
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<div>
|
|
<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">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
ENDOTHELIAL DIFFERENTIATION GENE 5; EDG5<br />
|
|
S1P RECEPTOR 2; S1P2
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
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</div>
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<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=S1PR2" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">S1PR2</a></em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/19/261?start=-3&limit=10&highlight=261">19p13.2</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr19:10221433-10231331&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'})">19:10,221,433-10,231,331</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
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|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
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|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/19/261?start=-3&limit=10&highlight=261">
|
|
19p13.2
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Deafness, autosomal recessive 68
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/610419"> 610419 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
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<p>The lysosphingolipid sphingosine 1-phosphate (S1P) regulates cell proliferation, apoptosis, motility, and neurite retraction. Its actions may be both intracellular as a second messenger and extracellular as a receptor ligand. S1P and the structurally related lysolipid mediator lysophosphatidic acid (LPA) signal cells through a set of G protein-coupled receptors known as EDG receptors. Some EDG receptors (e.g., EDG1, <a href="/entry/601974">601974</a>) are S1P receptors; others (e.g., EDG2, <a href="/entry/602282">602282</a>) are LPA receptors (summary by <a href="#3" class="mim-tip-reference" title="Chun, J., Goetzl, E. J., Hla, T., Igarashi, Y., Lynch, K. R., Moolenaar, W., Pyne, S., Tigyi, G. <strong>International Union of Pharmacology. XXXIV. Lysophospholipid receptor nomenclature.</strong> Pharm. Rev. 54: 265-269, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12037142/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12037142</a>] [<a href="https://doi.org/10.1124/pr.54.2.265" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12037142">Chun et al., 2002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12037142" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#3" class="mim-tip-reference" title="Chun, J., Goetzl, E. J., Hla, T., Igarashi, Y., Lynch, K. R., Moolenaar, W., Pyne, S., Tigyi, G. <strong>International Union of Pharmacology. XXXIV. Lysophospholipid receptor nomenclature.</strong> Pharm. Rev. 54: 265-269, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12037142/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12037142</a>] [<a href="https://doi.org/10.1124/pr.54.2.265" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12037142">Chun et al. (2002)</a> proposed a nomenclature scheme for the LPA and S1P receptors that is consistent with the International Union of Pharmacology (IUP) guidelines. According to these guidelines, a receptor is to be named with the abbreviation of the natural agonist with the highest potency, followed by a subscripted arabic number. Thus they suggested that the designation EDG5 should be changed to S1P2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12037142" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By screening a rat hippocampal cDNA library with a rat D2 dopamine receptor probe, followed by RT-PCR, <a href="#9" class="mim-tip-reference" title="MacLennan, A. J., Browe, C. S., Gaskin, A. A., Lado, D. C., Shaw, G. <strong>Cloning and characterization of a putative G-protein coupled receptor potentially involved in development.</strong> Molec. Cell. Neurosci. 5: 201-209, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8087418/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8087418</a>] [<a href="https://doi.org/10.1006/mcne.1994.1024" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8087418">MacLennan et al. (1994)</a> obtained a cDNA that they designated H218. Northern blot analysis of rat brain at different stages of development detected a 3.2-kb H218 transcript at all stages; expression was higher during brain embryogenesis than during later periods of brain development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8087418" 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 RT-PCR with degenerate primers based on the H218 sequence, <a href="#1" class="mim-tip-reference" title="An, S., Zheng, Y., Bleu, T. <strong>Sphingosine 1-phosphate-induced cell proliferation, survival, and related signaling events mediated by G protein-coupled receptors Edg3 and Edg5.</strong> J. Biol. Chem. 275: 288-296, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10617617/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10617617</a>] [<a href="https://doi.org/10.1074/jbc.275.1.288" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10617617">An et al. (2000)</a> isolated a cDNA encoding human EDG5. The predicted 353-amino acid EDG5 protein shares 92% amino acid identity with rat H218, approximately 44% identity with the human S1P receptors EDG1 and EDG3 (<a href="/entry/601965">601965</a>), and approximately 34% identity with the LPA receptors EDG2 and EDG4 (<a href="/entry/605110">605110</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10617617" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By functional analysis, <a href="#1" class="mim-tip-reference" title="An, S., Zheng, Y., Bleu, T. <strong>Sphingosine 1-phosphate-induced cell proliferation, survival, and related signaling events mediated by G protein-coupled receptors Edg3 and Edg5.</strong> J. Biol. Chem. 275: 288-296, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10617617/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10617617</a>] [<a href="https://doi.org/10.1074/jbc.275.1.288" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10617617">An et al. (2000)</a> showed that EDG5 and EDG3 transduce, at least in part, S1P-induced cell proliferation, survival, and transcriptional activation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10617617" 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>By microinjection of EDG mRNA into Xenopus oocytes, <a href="#2" class="mim-tip-reference" title="Ancellin, N., Hla, T. <strong>Differential pharmacological properties and signal transduction of the sphingosine 1-phosphate receptors EDG-1, EDG-3, and EDG-5.</strong> J. Biol. Chem. 274: 18997-19002, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10383399/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10383399</a>] [<a href="https://doi.org/10.1074/jbc.274.27.18997" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10383399">Ancellin and Hla (1999)</a> determined that human EDG3 and rat Edg5, but not human EDG1, conferred S1P-responsive intracellular calcium transients. All 3 EDGs were also activated by sphingosylphosphorylcholine (SPC), albeit at higher concentrations. <a href="#2" class="mim-tip-reference" title="Ancellin, N., Hla, T. <strong>Differential pharmacological properties and signal transduction of the sphingosine 1-phosphate receptors EDG-1, EDG-3, and EDG-5.</strong> J. Biol. Chem. 274: 18997-19002, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10383399/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10383399</a>] [<a href="https://doi.org/10.1074/jbc.274.27.18997" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10383399">Ancellin and Hla (1999)</a> also found evidence that the 3 receptors signal differentially by coupling to different G proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10383399" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Himmel, H. M., Meyer Zu Heringdorf, D., Graf, E., Dobrev, D., Kortner, A., Schuler, S., Jakobs, K. H., Ravens, U. <strong>Evidence for Edg-3 receptor-mediate d activation of I(K.ACh) by sphingosine-1-phosphate in human atrial cardiomyocytes.</strong> Molec. Pharm. 58: 449-454, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10908314/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10908314</a>] [<a href="https://doi.org/10.1124/mol.58.2.449" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10908314">Himmel et al. (2000)</a> investigated the sphingolipid-induced activation of inward rectifier K+ currents, or I(K.ACh), in freshly isolated guinea pig, mouse, and human atrial myocytes. S1P activated I(K.ACh) in atrial myocytes from all 3 species, and activation of human myocytes by S1P was blocked by the EDG3-selective antagonist suramin. SPC also activated I(K.ACh) currents in guinea pig myocytes, but was almost ineffective in mouse and human myocytes. PCR analysis identified EDG1, EDG3, and EDG5 transcripts in human atrial cells. The authors concluded that myocyte activation by S1P and SPC exhibits large species differences and that the S1P-induced I(K.ACh) activation in human atrial myocytes is mediated by EDG3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10908314" 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="Sanchez, T., Thangada, S., Wu, M.-T., Kontos, C. D., Wu, D., Wu, H., Hla, T. <strong>PTEN as an effector in the signaling of antimigratory G protein-coupled receptor.</strong> Proc. Nat. Acad. Sci. 102: 4312-4317, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15764699/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15764699</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15764699[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.0409784102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15764699">Sanchez et al. (2005)</a> found that the inhibitory effect of S1P on mammalian cell migration required PTEN (<a href="/entry/601728">601728</a>) as a signaling intermediate downstream of EDG5 and Rho GTPase activation. S1P activation of EDG5 stimulated complex formation between EDG5 and PTEN in the membrane compartment, and EDG5 signaling increased PTEN phosphorylation and its phosphatase activity in membrane fractions. <a href="#11" class="mim-tip-reference" title="Sanchez, T., Thangada, S., Wu, M.-T., Kontos, C. D., Wu, D., Wu, H., Hla, T. <strong>PTEN as an effector in the signaling of antimigratory G protein-coupled receptor.</strong> Proc. Nat. Acad. Sci. 102: 4312-4317, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15764699/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15764699</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15764699[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.0409784102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15764699">Sanchez et al. (2005)</a> concluded that EDG5 regulates PTEN by a Rho GTPase-dependent pathway to inhibit cell migration. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15764699" 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="#10" class="mim-tip-reference" title="Oskeritzian, C. A., Price, M. M., Hait, N. C., Kapitonov, D., Falanga, Y. T., Morales, J. K., Ryan, J. J., Milstien, S., Spiegel, S. <strong>Essential roles of sphingosine-1-phosphate receptor 2 in human mast cell activation, anaphylaxis, and pulmonary edema.</strong> J. Exp. Med. 207: 465-474, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20194630/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20194630</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20194630[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/10.1084/jem.20091513" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20194630">Oskeritzian et al. (2010)</a> found that treatment of human skin mast cells with an S1P2 antagonist or small interfering RNA against S1P2 greatly reduced secretion of CCL2 (<a href="/entry/158105">158105</a>), TNF (<a href="/entry/191160">191160</a>), and IL6 (<a href="/entry/147620">147620</a>) following stimulation with antigen and S1P. In contrast, they found that S1P1 (S1PR1; <a href="/entry/601974">601974</a>) was involved in mast cell migration, but not activation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20194630" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In 2 consanguineous Pakistani families segregating autosomal recessive deafness mapping to chromosome 19p13 (DFNB68; <a href="/entry/610419">610419</a>), <a href="#13" class="mim-tip-reference" title="Santos-Cortez, R. L. P., Faridi, R., Rehman, A. U., Lee, K., Ansar, M., Wang, X., Morell, R. J., Isaacson, R., Belyantseva, I. A., Dai, H., Acharya, A., Qaiser, T. A., and 15 others. <strong>Autosomal-recessive hearing impairment due to rare missense variants within S1PR2.</strong> Am. J. Hum. Genet. 98: 331-338, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26805784/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26805784</a>] [<a href="https://doi.org/10.1016/j.ajhg.2015.12.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26805784">Santos-Cortez et al. (2016)</a> identified homozygosity for 2 different missense mutations in the S1PR2 gene, R108P (<a href="#0001">605111.0001</a>) and Y140C (<a href="#0002">605111.0002</a>), that segregated with disease in the respective families and were not found in Pakistani controls or in public databases. In 1 of the families, affected individuals also exhibited severe asymmetric lower limb malformations; however, noting that gross limb deformities were not observed in the other family or in S1pr2-null mice, <a href="#13" class="mim-tip-reference" title="Santos-Cortez, R. L. P., Faridi, R., Rehman, A. U., Lee, K., Ansar, M., Wang, X., Morell, R. J., Isaacson, R., Belyantseva, I. A., Dai, H., Acharya, A., Qaiser, T. A., and 15 others. <strong>Autosomal-recessive hearing impairment due to rare missense variants within S1PR2.</strong> Am. J. Hum. Genet. 98: 331-338, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26805784/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26805784</a>] [<a href="https://doi.org/10.1016/j.ajhg.2015.12.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26805784">Santos-Cortez et al. (2016)</a> suggested that the limb deformities were not due to the mutation in S1PR2 but rather to a variant in another gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26805784" 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>Coordinated cell migration is essential in many fundamental biologic processes, including embryonic development, organogenesis, wound healing, and the immune response. During organogenesis, groups of cells are directed to specific locations within the embryo. <a href="#8" class="mim-tip-reference" title="Kupperman, E., An, S., Osborne, N., Waldron, S., Stainier, D. Y. R. <strong>A sphingosine-1-phosphate receptor regulates cell migration during vertebrate heart development.</strong> Nature 406: 192-195, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10910360/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10910360</a>] [<a href="https://doi.org/10.1038/35018092" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10910360">Kupperman et al. (2000)</a> demonstrated that the zebrafish 'miles apart' (mil) mutation specifically affects migration of heart precursors to the midline. They found that mutant cells transplanted into a wildtype embryo migrate normally and that wildtype cells in the mutant embryo fail to migrate, suggesting that mil may be involved in generating an environment permissive for migration. <a href="#8" class="mim-tip-reference" title="Kupperman, E., An, S., Osborne, N., Waldron, S., Stainier, D. Y. R. <strong>A sphingosine-1-phosphate receptor regulates cell migration during vertebrate heart development.</strong> Nature 406: 192-195, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10910360/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10910360</a>] [<a href="https://doi.org/10.1038/35018092" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10910360">Kupperman et al. (2000)</a> isolated mil by positional cloning and showed that it encodes a member of the lysosphingolipid G protein-coupled receptor family. The authors also showed that S1P is a ligand for mil, and that it activates several downstream signaling events that are not activated by the mutant alleles. <a href="#8" class="mim-tip-reference" title="Kupperman, E., An, S., Osborne, N., Waldron, S., Stainier, D. Y. R. <strong>A sphingosine-1-phosphate receptor regulates cell migration during vertebrate heart development.</strong> Nature 406: 192-195, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10910360/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10910360</a>] [<a href="https://doi.org/10.1038/35018092" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10910360">Kupperman et al. (2000)</a> determined that 1 of the 2 fully penetrant recessive alleles of mil, mil(m93), carries a substitution within the E/DRY motif. This motif, found in almost all members of the rhodopsin (<a href="/entry/180380">180380</a>)-like class of G protein-coupled receptors, is critical for receptor-G-protein coupling; therefore, the phenotype seen in mil(m93) mutants is due to mil being unable to couple to downstream G proteins. The expression pattern of mil is complex and dynamic. Maternal mil expression is found in a diffuse pattern throughout the blastoderm, and this pattern persists through the onset of gastrulation. More pronounced expression can be seen at tailbud stage in the anterior portion of the embryo and along the embryonic axis, and at the 16-somite stage in the midbrain/hindbrain boundary and the tip of the tail, where blisters later develop in mil mutants. At the 18-somite stage, expression appears just lateral to the midline, and as the myocardial precursors migrate to the midline, their location overlaps with this domain of mil expression. <a href="#8" class="mim-tip-reference" title="Kupperman, E., An, S., Osborne, N., Waldron, S., Stainier, D. Y. R. <strong>A sphingosine-1-phosphate receptor regulates cell migration during vertebrate heart development.</strong> Nature 406: 192-195, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10910360/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10910360</a>] [<a href="https://doi.org/10.1038/35018092" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10910360">Kupperman et al. (2000)</a> suggested that their data revealed a new role for lysosphingolipids in regulating cell migration during vertebrate development and provided the first molecular clues into the fusion of the bilateral heart primordia during organogenesis of the heart. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10910360" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Ishii, I., Ye, X., Friedman, B., Kawamura, S., Contos, J. J. A., Kingsbury, M. A., Yang, A. H., Zhang, G., Brown, J. H., Chun, J. <strong>Marked perinatal lethality and cellular signaling deficits in mice null for the two sphingosine 1-phosphate (S1P) receptors, S1P-2/LP-B2/EDG-5 and S1P-3/LP-B3/EDG-3.</strong> J. Biol. Chem. 277: 25152-25159, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12006579/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12006579</a>] [<a href="https://doi.org/10.1074/jbc.M200137200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12006579">Ishii et al. (2002)</a> developed mice null for both Edg3 and Edg5. Mice deficient in Edg5 alone were viable and fertile and developed normally. The litter sizes from Edg5-Edg3 double-null crosses were remarkably reduced, and these pups often did not survive through infancy, although double-null survivors showed no obvious phenotype. <a href="#6" class="mim-tip-reference" title="Ishii, I., Ye, X., Friedman, B., Kawamura, S., Contos, J. J. A., Kingsbury, M. A., Yang, A. H., Zhang, G., Brown, J. H., Chun, J. <strong>Marked perinatal lethality and cellular signaling deficits in mice null for the two sphingosine 1-phosphate (S1P) receptors, S1P-2/LP-B2/EDG-5 and S1P-3/LP-B3/EDG-3.</strong> J. Biol. Chem. 277: 25152-25159, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12006579/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12006579</a>] [<a href="https://doi.org/10.1074/jbc.M200137200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12006579">Ishii et al. (2002)</a> concluded that either receptor subtype supports embryonic development, but deletion of both produces marked perinatal lethality. They examined mouse embryonic fibroblasts for the effects of receptor deletions on S1P signaling. Edg5 null fibroblasts showed a significant decrease in Rho (see <a href="/entry/602732">602732</a>) activation with exposure to S1P, and double-null fibroblasts displayed a complete loss of Rho activation and a significant decrease in phospholipase C (PLC; see <a href="/entry/600810">600810</a>) activation and calcium mobilization, with no effect on adenylyl cyclase inhibition. <a href="#6" class="mim-tip-reference" title="Ishii, I., Ye, X., Friedman, B., Kawamura, S., Contos, J. J. A., Kingsbury, M. A., Yang, A. H., Zhang, G., Brown, J. H., Chun, J. <strong>Marked perinatal lethality and cellular signaling deficits in mice null for the two sphingosine 1-phosphate (S1P) receptors, S1P-2/LP-B2/EDG-5 and S1P-3/LP-B3/EDG-3.</strong> J. Biol. Chem. 277: 25152-25159, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12006579/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12006579</a>] [<a href="https://doi.org/10.1074/jbc.M200137200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12006579">Ishii et al. (2002)</a> concluded that there is preferential coupling of Edg5 and Edg3 to Rho and PLC/Ca(2+) pathways, respectively, in the mouse. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12006579" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Goparaju, S. K., Jolly, P. S., Watterson, K. R., Bektas, M., Alvarez, S., Sarkar, S., Mel, L., Ishii, I., Chun, J., Milstien, S., Spiegel, S. <strong>The SIP2 receptor negatively regulates platelet-derived growth factor-induced motility and proliferation.</strong> Molec. Cell. Biol. 25: 4237-4249, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15870293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15870293</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15870293[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/10.1128/MCB.25.10.4237-4249.2005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15870293">Goparaju et al. (2005)</a> reported that loss of S1p2 in mice resulted in dramatically increased migration of fibroblasts to S1P, serum, and Pdgf (see <a href="/entry/173430">173430</a>), but not fibronectin (see <a href="/entry/135600">135600</a>), in a manner dependent on S1p1 and Sphk1 (<a href="/entry/603730">603730</a>). Cells lacking S1p2 exhibited enhanced proliferation and increased Sphk1 expression. <a href="#4" class="mim-tip-reference" title="Goparaju, S. K., Jolly, P. S., Watterson, K. R., Bektas, M., Alvarez, S., Sarkar, S., Mel, L., Ishii, I., Chun, J., Milstien, S., Spiegel, S. <strong>The SIP2 receptor negatively regulates platelet-derived growth factor-induced motility and proliferation.</strong> Molec. Cell. Biol. 25: 4237-4249, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15870293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15870293</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15870293[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/10.1128/MCB.25.10.4237-4249.2005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15870293">Goparaju et al. (2005)</a> concluded that S1P2 serves as a negative regulator of PDGF-induced migration and proliferation, as well as SPHK1 expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15870293" 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="Skoura, A., Sanchez, T., Claffey, K., Mandala, S. M., Proia, R. L., Hla, T. <strong>Essential role of sphingosine 1-phosphate receptor 2 in pathological angiogenesis of the mouse retina.</strong> J. Clin. Invest. 117: 2506-2516, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17710232/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17710232</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17710232[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/JCI31123" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17710232">Skoura et al. (2007)</a> found that the angiogenic process proceeded normally in S1p2 -/- mice during normal retinal development. However, when mice were exposed to ischemic stress, S1p2 -/- retinas had reduced pathologic intravitreal angiogenesis and apparently normal vascular development. S1p2 was required for inflammatory cell infiltration, induction of the proinflammatory and proangiogenic enzyme Cox2 (PTGS2; <a href="/entry/600262">600262</a>), and suppression of eNos (NOS3; <a href="/entry/163729">163729</a>), which produces the vasodilator nitric oxide. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17710232" 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="Kono, M., Belyantseva, I. A., Skoura, A., Frolenkov, G. I., Starost, M. F., Dreier, J. L., Lidington, D., Bolz, S.-S., Friedman, T. B., Hla, T., Proia, R. L. <strong>Deafness and stria vascularis defects in S1P2 receptor-null mice.</strong> J. Biol. Chem. 282: 10690-10696, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17284444/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17284444</a>] [<a href="https://doi.org/10.1074/jbc.M700370200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17284444">Kono et al. (2007)</a> showed that mice lacking S1p2 were deaf by 1 month of age. Some of the earliest lesions in cochlea were in the stria vascularis, a barrier epithelium containing the primary vasculature of the inner ear. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17284444" 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="#14" class="mim-tip-reference" title="Shimizu, T., Nakazawa, T., Cho, A., Dastvan, F., Shilling, D., Daum, G., Reidy, M. A. <strong>Sphingosine 1-phosphate receptor 2 negatively regulates neointimal formation in mouse arteries.</strong> Circ. Res. 101: 995-1000, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17872461/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17872461</a>] [<a href="https://doi.org/10.1161/CIRCRESAHA.107.159228" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17872461">Shimizu et al. (2007)</a> found that ligation of the left carotid artery in mice lacking S1p2 resulted in large neointimal lesions that were accompanied by a significant increase in both medial and intimal smooth muscle cell (SMC) replication and migration in response to S1P. <a href="#14" class="mim-tip-reference" title="Shimizu, T., Nakazawa, T., Cho, A., Dastvan, F., Shilling, D., Daum, G., Reidy, M. A. <strong>Sphingosine 1-phosphate receptor 2 negatively regulates neointimal formation in mouse arteries.</strong> Circ. Res. 101: 995-1000, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17872461/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17872461</a>] [<a href="https://doi.org/10.1161/CIRCRESAHA.107.159228" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17872461">Shimizu et al. (2007)</a> proposed that activation of S1P2 acts to suppress SMC growth in arteries and that S1P is a regulator of neointimal development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17872461" 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 S1p2-deficient mice, <a href="#10" class="mim-tip-reference" title="Oskeritzian, C. A., Price, M. M., Hait, N. C., Kapitonov, D., Falanga, Y. T., Morales, J. K., Ryan, J. J., Milstien, S., Spiegel, S. <strong>Essential roles of sphingosine-1-phosphate receptor 2 in human mast cell activation, anaphylaxis, and pulmonary edema.</strong> J. Exp. Med. 207: 465-474, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20194630/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20194630</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20194630[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/10.1084/jem.20091513" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20194630">Oskeritzian et al. (2010)</a> showed that anaphylactic responses triggered by IgE, such as histamine secretion and subsequent pulmonary edema, but not histamine- or platelet-activating factor-induced anaphylactic responses, required the S1p2 receptor. <a href="#10" class="mim-tip-reference" title="Oskeritzian, C. A., Price, M. M., Hait, N. C., Kapitonov, D., Falanga, Y. T., Morales, J. K., Ryan, J. J., Milstien, S., Spiegel, S. <strong>Essential roles of sphingosine-1-phosphate receptor 2 in human mast cell activation, anaphylaxis, and pulmonary edema.</strong> J. Exp. Med. 207: 465-474, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20194630/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20194630</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20194630[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/10.1084/jem.20091513" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20194630">Oskeritzian et al. (2010)</a> concluded that S1P and S1P1 are determinants of systemic anaphylaxis and pulmonary edema. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20194630" 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=605111[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<strong>.0001 DEAFNESS, AUTOSOMAL RECESSIVE 68</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">rs869312749 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs869312749;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=rs869312749" 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=rs869312749" 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=RCV000210066" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000210066" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000210066</a>
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<p>In affected members of a consanguineous Pakistani family (DEM4154) with congenital profound deafness mapping to chromosome 19 (DFNB68; <a href="/entry/610419">610419</a>) as well as severe asymmetric lower limb malformations, previously studied by <a href="#12" class="mim-tip-reference" title="Santos, R. L. P., Hassan, M. J., Sikandar, S., Lee, K., Ali, G., Martin, P. E., Jr., Wambangco, M. A. L., Ahmad, W., Leal, S. M. <strong>DFNB68, a novel autosomal recessive non-syndromic hearing impairment locus at chromosomal region 19p13.2.</strong> Hum. Genet. 120: 85-92, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16703383/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16703383</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16703383[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/10.1007/s00439-006-0188-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16703383">Santos et al. (2006)</a>, <a href="#13" class="mim-tip-reference" title="Santos-Cortez, R. L. P., Faridi, R., Rehman, A. U., Lee, K., Ansar, M., Wang, X., Morell, R. J., Isaacson, R., Belyantseva, I. A., Dai, H., Acharya, A., Qaiser, T. A., and 15 others. <strong>Autosomal-recessive hearing impairment due to rare missense variants within S1PR2.</strong> Am. J. Hum. Genet. 98: 331-338, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26805784/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26805784</a>] [<a href="https://doi.org/10.1016/j.ajhg.2015.12.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26805784">Santos-Cortez et al. (2016)</a> identified homozygosity for a c.323G-C transversion (c.323G-C, NM_004230.3) in the S1PR2 gene, resulting in an arg108-to-pro (R108P) substitution at a highly conserved residue within the third transmembrane domain (TM3) on the extracellular side. The mutation segregated with disease in the family and was not found in 720 Pakistani control chromosomes, in 76 in-house exomes from unrelated Pakistani individuals with nondeafness phenotypes, or in the dbSNP or ExAC databases. Noting that gross limb deformities were not observed in a second family with S1PR2-associated deafness or in S1pr2-null mice, <a href="#13" class="mim-tip-reference" title="Santos-Cortez, R. L. P., Faridi, R., Rehman, A. U., Lee, K., Ansar, M., Wang, X., Morell, R. J., Isaacson, R., Belyantseva, I. A., Dai, H., Acharya, A., Qaiser, T. A., and 15 others. <strong>Autosomal-recessive hearing impairment due to rare missense variants within S1PR2.</strong> Am. J. Hum. Genet. 98: 331-338, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26805784/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26805784</a>] [<a href="https://doi.org/10.1016/j.ajhg.2015.12.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26805784">Santos-Cortez et al. (2016)</a> suggested that the limb deformities were not due to the mutation in S1PR2 but rather to a variant in another gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=26805784+16703383" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<span class="mim-font">
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<strong>.0002 DEAFNESS, AUTOSOMAL RECESSIVE 68</strong>
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S1PR2, TYR140CYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs869312750 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs869312750;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=rs869312750" 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=rs869312750" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000210070" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000210070" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000210070</a>
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<p>In affected members of a consanguineous Pakistani family (PKDF1400) with congenital profound deafness mapping to chromosome 19 (DFNB68; <a href="/entry/610419">610419</a>), <a href="#13" class="mim-tip-reference" title="Santos-Cortez, R. L. P., Faridi, R., Rehman, A. U., Lee, K., Ansar, M., Wang, X., Morell, R. J., Isaacson, R., Belyantseva, I. A., Dai, H., Acharya, A., Qaiser, T. A., and 15 others. <strong>Autosomal-recessive hearing impairment due to rare missense variants within S1PR2.</strong> Am. J. Hum. Genet. 98: 331-338, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26805784/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26805784</a>] [<a href="https://doi.org/10.1016/j.ajhg.2015.12.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26805784">Santos-Cortez et al. (2016)</a> identified homozygosity for a c.419A-G transition (c.419A-G, NM_004230.3) in the S1PR2 gene, resulting in a tyr140-to-cys (Y140C) substitution at a highly conserved residue within intracellular loop 2 (ICL2). The mutation segregated with disease in the family and was not found in 720 Pakistani control chromosomes, in 76 in-house exomes from unrelated Pakistani individuals with nondeafness phenotypes, or in the dbSNP or ExAC databases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26805784" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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An, S., Zheng, Y., Bleu, T.
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[<a href="https://doi.org/10.1074/jbc.275.1.288" target="_blank">Full Text</a>]
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Ancellin, N., Hla, T.
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<strong>Differential pharmacological properties and signal transduction of the sphingosine 1-phosphate receptors EDG-1, EDG-3, and EDG-5.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10383399/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10383399</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10383399" 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/10.1074/jbc.274.27.18997" target="_blank">Full Text</a>]
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Chun, J., Goetzl, E. J., Hla, T., Igarashi, Y., Lynch, K. R., Moolenaar, W., Pyne, S., Tigyi, G.
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<strong>International Union of Pharmacology. XXXIV. Lysophospholipid receptor nomenclature.</strong>
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Pharm. Rev. 54: 265-269, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12037142/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12037142</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12037142" 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/10.1124/pr.54.2.265" target="_blank">Full Text</a>]
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Goparaju, S. K., Jolly, P. S., Watterson, K. R., Bektas, M., Alvarez, S., Sarkar, S., Mel, L., Ishii, I., Chun, J., Milstien, S., Spiegel, S.
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<strong>The SIP2 receptor negatively regulates platelet-derived growth factor-induced motility and proliferation.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15870293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15870293</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15870293[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=15870293" 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/10.1128/MCB.25.10.4237-4249.2005" target="_blank">Full Text</a>]
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<a id="Himmel2000" class="mim-anchor"></a>
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Himmel, H. M., Meyer Zu Heringdorf, D., Graf, E., Dobrev, D., Kortner, A., Schuler, S., Jakobs, K. H., Ravens, U.
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<strong>Evidence for Edg-3 receptor-mediate d activation of I(K.ACh) by sphingosine-1-phosphate in human atrial cardiomyocytes.</strong>
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Molec. Pharm. 58: 449-454, 2000.
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[<a href="https://doi.org/10.1124/mol.58.2.449" target="_blank">Full Text</a>]
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Ishii, I., Ye, X., Friedman, B., Kawamura, S., Contos, J. J. A., Kingsbury, M. A., Yang, A. H., Zhang, G., Brown, J. H., Chun, J.
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<strong>Marked perinatal lethality and cellular signaling deficits in mice null for the two sphingosine 1-phosphate (S1P) receptors, S1P-2/LP-B2/EDG-5 and S1P-3/LP-B3/EDG-3.</strong>
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[<a href="https://doi.org/10.1074/jbc.M200137200" target="_blank">Full Text</a>]
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Kono, M., Belyantseva, I. A., Skoura, A., Frolenkov, G. I., Starost, M. F., Dreier, J. L., Lidington, D., Bolz, S.-S., Friedman, T. B., Hla, T., Proia, R. L.
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[<a href="https://doi.org/10.1074/jbc.M700370200" target="_blank">Full Text</a>]
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Kupperman, E., An, S., Osborne, N., Waldron, S., Stainier, D. Y. R.
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<strong>A sphingosine-1-phosphate receptor regulates cell migration during vertebrate heart development.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10910360/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10910360</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10910360" 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/10.1038/35018092" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="9" class="mim-anchor"></a>
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<a id="MacLennan1994" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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MacLennan, A. J., Browe, C. S., Gaskin, A. A., Lado, D. C., Shaw, G.
|
|
<strong>Cloning and characterization of a putative G-protein coupled receptor potentially involved in development.</strong>
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Molec. Cell. Neurosci. 5: 201-209, 1994.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8087418/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8087418</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8087418" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1006/mcne.1994.1024" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="10" class="mim-anchor"></a>
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<a id="Oskeritzian2010" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Oskeritzian, C. A., Price, M. M., Hait, N. C., Kapitonov, D., Falanga, Y. T., Morales, J. K., Ryan, J. J., Milstien, S., Spiegel, S.
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<strong>Essential roles of sphingosine-1-phosphate receptor 2 in human mast cell activation, anaphylaxis, and pulmonary edema.</strong>
|
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J. Exp. Med. 207: 465-474, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20194630/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20194630</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20194630[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=20194630" 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/10.1084/jem.20091513" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="11" class="mim-anchor"></a>
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<a id="Sanchez2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Sanchez, T., Thangada, S., Wu, M.-T., Kontos, C. D., Wu, D., Wu, H., Hla, T.
|
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<strong>PTEN as an effector in the signaling of antimigratory G protein-coupled receptor.</strong>
|
|
Proc. Nat. Acad. Sci. 102: 4312-4317, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15764699/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15764699</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15764699[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=15764699" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.0409784102" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="12" class="mim-anchor"></a>
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<a id="Santos2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Santos, R. L. P., Hassan, M. J., Sikandar, S., Lee, K., Ali, G., Martin, P. E., Jr., Wambangco, M. A. L., Ahmad, W., Leal, S. M.
|
|
<strong>DFNB68, a novel autosomal recessive non-syndromic hearing impairment locus at chromosomal region 19p13.2.</strong>
|
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Hum. Genet. 120: 85-92, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16703383/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16703383</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16703383[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=16703383" 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/10.1007/s00439-006-0188-z" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="13" class="mim-anchor"></a>
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<a id="Santos-Cortez2016" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Santos-Cortez, R. L. P., Faridi, R., Rehman, A. U., Lee, K., Ansar, M., Wang, X., Morell, R. J., Isaacson, R., Belyantseva, I. A., Dai, H., Acharya, A., Qaiser, T. A., and 15 others.
|
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<strong>Autosomal-recessive hearing impairment due to rare missense variants within S1PR2.</strong>
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Am. J. Hum. Genet. 98: 331-338, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26805784/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26805784</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26805784" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ajhg.2015.12.004" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="14" class="mim-anchor"></a>
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<a id="Shimizu2007" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Shimizu, T., Nakazawa, T., Cho, A., Dastvan, F., Shilling, D., Daum, G., Reidy, M. A.
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<strong>Sphingosine 1-phosphate receptor 2 negatively regulates neointimal formation in mouse arteries.</strong>
|
|
Circ. Res. 101: 995-1000, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17872461/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17872461</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17872461" 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/CIRCRESAHA.107.159228" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="15" class="mim-anchor"></a>
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<a id="Skoura2007" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Skoura, A., Sanchez, T., Claffey, K., Mandala, S. M., Proia, R. L., Hla, T.
|
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<strong>Essential role of sphingosine 1-phosphate receptor 2 in pathological angiogenesis of the mouse retina.</strong>
|
|
J. Clin. Invest. 117: 2506-2516, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17710232/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17710232</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17710232[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=17710232" 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/10.1172/JCI31123" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 03/15/2016
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Paul J. Converse - updated : 11/3/2010<br>Patricia A. Hartz - updated : 11/6/2007<br>Patricia A. Hartz - updated : 5/9/2005<br>Patricia A. Hartz - updated : 8/19/2002<br>Ada Hamosh - updated : 7/13/2000<br>Paul J. Converse - updated : 7/10/2000
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
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<span class="text-nowrap mim-text-font">
|
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Creation Date:
|
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</span>
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</div>
|
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
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Paul J. Converse : 7/6/2000
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
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</span>
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</div>
|
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
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carol : 10/19/2017
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
|
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
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|
carol : 03/15/2016<br>alopez : 11/30/2015<br>carol : 5/7/2014<br>mgross : 11/4/2010<br>terry : 11/3/2010<br>alopez : 5/5/2009<br>alopez : 5/4/2009<br>terry : 4/28/2009<br>wwang : 9/25/2008<br>carol : 2/29/2008<br>carol : 2/29/2008<br>mgross : 11/6/2007<br>terry : 11/6/2007<br>mgross : 5/10/2005<br>terry : 5/9/2005<br>tkritzer : 3/5/2004<br>alopez : 1/21/2004<br>mgross : 8/19/2002<br>alopez : 7/13/2000<br>alopez : 7/13/2000<br>psherman : 7/11/2000<br>mgross : 7/10/2000<br>mgross : 7/10/2000<br>mgross : 7/6/2000
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 605111
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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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SPHINGOSINE-1-PHOSPHATE RECEPTOR 2; S1PR2
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
ENDOTHELIAL DIFFERENTIATION GENE 5; EDG5<br />
|
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S1P RECEPTOR 2; S1P2
|
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</span>
|
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</h4>
|
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: S1PR2</em></strong>
|
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 19p13.2
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Genomic coordinates <span class="small">(GRCh38)</span> : 19:10,221,433-10,231,331 </span>
|
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</em>
|
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</strong>
|
|
<span class="small">(from NCBI)</span>
|
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</h4>
|
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<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
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<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
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</th>
|
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<th>
|
|
Phenotype
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</th>
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<th>
|
|
Phenotype <br /> MIM number
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</th>
|
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<th>
|
|
Inheritance
|
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</th>
|
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<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
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</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
19p13.2
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Deafness, autosomal recessive 68
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
610419
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
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</tr>
|
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|
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|
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</tbody>
|
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
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</h4>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<span class="mim-text-font">
|
|
<p>The lysosphingolipid sphingosine 1-phosphate (S1P) regulates cell proliferation, apoptosis, motility, and neurite retraction. Its actions may be both intracellular as a second messenger and extracellular as a receptor ligand. S1P and the structurally related lysolipid mediator lysophosphatidic acid (LPA) signal cells through a set of G protein-coupled receptors known as EDG receptors. Some EDG receptors (e.g., EDG1, 601974) are S1P receptors; others (e.g., EDG2, 602282) are LPA receptors (summary by Chun et al., 2002). </p>
|
|
</span>
|
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<div>
|
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<br />
|
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
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<strong>Nomenclature</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>Chun et al. (2002) proposed a nomenclature scheme for the LPA and S1P receptors that is consistent with the International Union of Pharmacology (IUP) guidelines. According to these guidelines, a receptor is to be named with the abbreviation of the natural agonist with the highest potency, followed by a subscripted arabic number. Thus they suggested that the designation EDG5 should be changed to S1P2. </p>
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</span>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>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>By screening a rat hippocampal cDNA library with a rat D2 dopamine receptor probe, followed by RT-PCR, MacLennan et al. (1994) obtained a cDNA that they designated H218. Northern blot analysis of rat brain at different stages of development detected a 3.2-kb H218 transcript at all stages; expression was higher during brain embryogenesis than during later periods of brain development. </p><p>Using RT-PCR with degenerate primers based on the H218 sequence, An et al. (2000) isolated a cDNA encoding human EDG5. The predicted 353-amino acid EDG5 protein shares 92% amino acid identity with rat H218, approximately 44% identity with the human S1P receptors EDG1 and EDG3 (601965), and approximately 34% identity with the LPA receptors EDG2 and EDG4 (605110). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By functional analysis, An et al. (2000) showed that EDG5 and EDG3 transduce, at least in part, S1P-induced cell proliferation, survival, and transcriptional activation. </p><p>By microinjection of EDG mRNA into Xenopus oocytes, Ancellin and Hla (1999) determined that human EDG3 and rat Edg5, but not human EDG1, conferred S1P-responsive intracellular calcium transients. All 3 EDGs were also activated by sphingosylphosphorylcholine (SPC), albeit at higher concentrations. Ancellin and Hla (1999) also found evidence that the 3 receptors signal differentially by coupling to different G proteins. </p><p>Himmel et al. (2000) investigated the sphingolipid-induced activation of inward rectifier K+ currents, or I(K.ACh), in freshly isolated guinea pig, mouse, and human atrial myocytes. S1P activated I(K.ACh) in atrial myocytes from all 3 species, and activation of human myocytes by S1P was blocked by the EDG3-selective antagonist suramin. SPC also activated I(K.ACh) currents in guinea pig myocytes, but was almost ineffective in mouse and human myocytes. PCR analysis identified EDG1, EDG3, and EDG5 transcripts in human atrial cells. The authors concluded that myocyte activation by S1P and SPC exhibits large species differences and that the S1P-induced I(K.ACh) activation in human atrial myocytes is mediated by EDG3. </p><p>Sanchez et al. (2005) found that the inhibitory effect of S1P on mammalian cell migration required PTEN (601728) as a signaling intermediate downstream of EDG5 and Rho GTPase activation. S1P activation of EDG5 stimulated complex formation between EDG5 and PTEN in the membrane compartment, and EDG5 signaling increased PTEN phosphorylation and its phosphatase activity in membrane fractions. Sanchez et al. (2005) concluded that EDG5 regulates PTEN by a Rho GTPase-dependent pathway to inhibit cell migration. </p><p>Oskeritzian et al. (2010) found that treatment of human skin mast cells with an S1P2 antagonist or small interfering RNA against S1P2 greatly reduced secretion of CCL2 (158105), TNF (191160), and IL6 (147620) following stimulation with antigen and S1P. In contrast, they found that S1P1 (S1PR1; 601974) was involved in mast cell migration, but not activation. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In 2 consanguineous Pakistani families segregating autosomal recessive deafness mapping to chromosome 19p13 (DFNB68; 610419), Santos-Cortez et al. (2016) identified homozygosity for 2 different missense mutations in the S1PR2 gene, R108P (605111.0001) and Y140C (605111.0002), that segregated with disease in the respective families and were not found in Pakistani controls or in public databases. In 1 of the families, affected individuals also exhibited severe asymmetric lower limb malformations; however, noting that gross limb deformities were not observed in the other family or in S1pr2-null mice, Santos-Cortez et al. (2016) suggested that the limb deformities were not due to the mutation in S1PR2 but rather to a variant in another gene. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Coordinated cell migration is essential in many fundamental biologic processes, including embryonic development, organogenesis, wound healing, and the immune response. During organogenesis, groups of cells are directed to specific locations within the embryo. Kupperman et al. (2000) demonstrated that the zebrafish 'miles apart' (mil) mutation specifically affects migration of heart precursors to the midline. They found that mutant cells transplanted into a wildtype embryo migrate normally and that wildtype cells in the mutant embryo fail to migrate, suggesting that mil may be involved in generating an environment permissive for migration. Kupperman et al. (2000) isolated mil by positional cloning and showed that it encodes a member of the lysosphingolipid G protein-coupled receptor family. The authors also showed that S1P is a ligand for mil, and that it activates several downstream signaling events that are not activated by the mutant alleles. Kupperman et al. (2000) determined that 1 of the 2 fully penetrant recessive alleles of mil, mil(m93), carries a substitution within the E/DRY motif. This motif, found in almost all members of the rhodopsin (180380)-like class of G protein-coupled receptors, is critical for receptor-G-protein coupling; therefore, the phenotype seen in mil(m93) mutants is due to mil being unable to couple to downstream G proteins. The expression pattern of mil is complex and dynamic. Maternal mil expression is found in a diffuse pattern throughout the blastoderm, and this pattern persists through the onset of gastrulation. More pronounced expression can be seen at tailbud stage in the anterior portion of the embryo and along the embryonic axis, and at the 16-somite stage in the midbrain/hindbrain boundary and the tip of the tail, where blisters later develop in mil mutants. At the 18-somite stage, expression appears just lateral to the midline, and as the myocardial precursors migrate to the midline, their location overlaps with this domain of mil expression. Kupperman et al. (2000) suggested that their data revealed a new role for lysosphingolipids in regulating cell migration during vertebrate development and provided the first molecular clues into the fusion of the bilateral heart primordia during organogenesis of the heart. </p><p>Ishii et al. (2002) developed mice null for both Edg3 and Edg5. Mice deficient in Edg5 alone were viable and fertile and developed normally. The litter sizes from Edg5-Edg3 double-null crosses were remarkably reduced, and these pups often did not survive through infancy, although double-null survivors showed no obvious phenotype. Ishii et al. (2002) concluded that either receptor subtype supports embryonic development, but deletion of both produces marked perinatal lethality. They examined mouse embryonic fibroblasts for the effects of receptor deletions on S1P signaling. Edg5 null fibroblasts showed a significant decrease in Rho (see 602732) activation with exposure to S1P, and double-null fibroblasts displayed a complete loss of Rho activation and a significant decrease in phospholipase C (PLC; see 600810) activation and calcium mobilization, with no effect on adenylyl cyclase inhibition. Ishii et al. (2002) concluded that there is preferential coupling of Edg5 and Edg3 to Rho and PLC/Ca(2+) pathways, respectively, in the mouse. </p><p>Goparaju et al. (2005) reported that loss of S1p2 in mice resulted in dramatically increased migration of fibroblasts to S1P, serum, and Pdgf (see 173430), but not fibronectin (see 135600), in a manner dependent on S1p1 and Sphk1 (603730). Cells lacking S1p2 exhibited enhanced proliferation and increased Sphk1 expression. Goparaju et al. (2005) concluded that S1P2 serves as a negative regulator of PDGF-induced migration and proliferation, as well as SPHK1 expression. </p><p>Skoura et al. (2007) found that the angiogenic process proceeded normally in S1p2 -/- mice during normal retinal development. However, when mice were exposed to ischemic stress, S1p2 -/- retinas had reduced pathologic intravitreal angiogenesis and apparently normal vascular development. S1p2 was required for inflammatory cell infiltration, induction of the proinflammatory and proangiogenic enzyme Cox2 (PTGS2; 600262), and suppression of eNos (NOS3; 163729), which produces the vasodilator nitric oxide. </p><p>Kono et al. (2007) showed that mice lacking S1p2 were deaf by 1 month of age. Some of the earliest lesions in cochlea were in the stria vascularis, a barrier epithelium containing the primary vasculature of the inner ear. </p><p>Shimizu et al. (2007) found that ligation of the left carotid artery in mice lacking S1p2 resulted in large neointimal lesions that were accompanied by a significant increase in both medial and intimal smooth muscle cell (SMC) replication and migration in response to S1P. Shimizu et al. (2007) proposed that activation of S1P2 acts to suppress SMC growth in arteries and that S1P is a regulator of neointimal development. </p><p>Using S1p2-deficient mice, Oskeritzian et al. (2010) showed that anaphylactic responses triggered by IgE, such as histamine secretion and subsequent pulmonary edema, but not histamine- or platelet-activating factor-induced anaphylactic responses, required the S1p2 receptor. Oskeritzian et al. (2010) concluded that S1P and S1P1 are determinants of systemic anaphylaxis and pulmonary edema. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>2 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 DEAFNESS, AUTOSOMAL RECESSIVE 68</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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S1PR2, ARG108PRO
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<br />
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SNP: rs869312749,
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ClinVar: RCV000210066
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In affected members of a consanguineous Pakistani family (DEM4154) with congenital profound deafness mapping to chromosome 19 (DFNB68; 610419) as well as severe asymmetric lower limb malformations, previously studied by Santos et al. (2006), Santos-Cortez et al. (2016) identified homozygosity for a c.323G-C transversion (c.323G-C, NM_004230.3) in the S1PR2 gene, resulting in an arg108-to-pro (R108P) substitution at a highly conserved residue within the third transmembrane domain (TM3) on the extracellular side. The mutation segregated with disease in the family and was not found in 720 Pakistani control chromosomes, in 76 in-house exomes from unrelated Pakistani individuals with nondeafness phenotypes, or in the dbSNP or ExAC databases. Noting that gross limb deformities were not observed in a second family with S1PR2-associated deafness or in S1pr2-null mice, Santos-Cortez et al. (2016) suggested that the limb deformities were not due to the mutation in S1PR2 but rather to a variant in another gene. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0002 DEAFNESS, AUTOSOMAL RECESSIVE 68</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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S1PR2, TYR140CYS
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<br />
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SNP: rs869312750,
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ClinVar: RCV000210070
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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|
<p>In affected members of a consanguineous Pakistani family (PKDF1400) with congenital profound deafness mapping to chromosome 19 (DFNB68; 610419), Santos-Cortez et al. (2016) identified homozygosity for a c.419A-G transition (c.419A-G, NM_004230.3) in the S1PR2 gene, resulting in a tyr140-to-cys (Y140C) substitution at a highly conserved residue within intracellular loop 2 (ICL2). The mutation segregated with disease in the family and was not found in 720 Pakistani control chromosomes, in 76 in-house exomes from unrelated Pakistani individuals with nondeafness phenotypes, or in the dbSNP or ExAC databases. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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An, S., Zheng, Y., Bleu, T.
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<strong>Sphingosine 1-phosphate-induced cell proliferation, survival, and related signaling events mediated by G protein-coupled receptors Edg3 and Edg5.</strong>
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J. Biol. Chem. 275: 288-296, 2000.
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<p class="mim-text-font">
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Ancellin, N., Hla, T.
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<strong>Differential pharmacological properties and signal transduction of the sphingosine 1-phosphate receptors EDG-1, EDG-3, and EDG-5.</strong>
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J. Biol. Chem. 274: 18997-19002, 1999.
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Chun, J., Goetzl, E. J., Hla, T., Igarashi, Y., Lynch, K. R., Moolenaar, W., Pyne, S., Tigyi, G.
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<strong>International Union of Pharmacology. XXXIV. Lysophospholipid receptor nomenclature.</strong>
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Pharm. Rev. 54: 265-269, 2002.
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Goparaju, S. K., Jolly, P. S., Watterson, K. R., Bektas, M., Alvarez, S., Sarkar, S., Mel, L., Ishii, I., Chun, J., Milstien, S., Spiegel, S.
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<strong>The SIP2 receptor negatively regulates platelet-derived growth factor-induced motility and proliferation.</strong>
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Molec. Cell. Biol. 25: 4237-4249, 2005.
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Himmel, H. M., Meyer Zu Heringdorf, D., Graf, E., Dobrev, D., Kortner, A., Schuler, S., Jakobs, K. H., Ravens, U.
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<strong>Evidence for Edg-3 receptor-mediate d activation of I(K.ACh) by sphingosine-1-phosphate in human atrial cardiomyocytes.</strong>
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Molec. Pharm. 58: 449-454, 2000.
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[Full Text: https://doi.org/10.1124/mol.58.2.449]
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Ishii, I., Ye, X., Friedman, B., Kawamura, S., Contos, J. J. A., Kingsbury, M. A., Yang, A. H., Zhang, G., Brown, J. H., Chun, J.
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<strong>Marked perinatal lethality and cellular signaling deficits in mice null for the two sphingosine 1-phosphate (S1P) receptors, S1P-2/LP-B2/EDG-5 and S1P-3/LP-B3/EDG-3.</strong>
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J. Biol. Chem. 277: 25152-25159, 2002.
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Kono, M., Belyantseva, I. A., Skoura, A., Frolenkov, G. I., Starost, M. F., Dreier, J. L., Lidington, D., Bolz, S.-S., Friedman, T. B., Hla, T., Proia, R. L.
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<strong>Deafness and stria vascularis defects in S1P2 receptor-null mice.</strong>
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J. Biol. Chem. 282: 10690-10696, 2007.
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Kupperman, E., An, S., Osborne, N., Waldron, S., Stainier, D. Y. R.
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<strong>A sphingosine-1-phosphate receptor regulates cell migration during vertebrate heart development.</strong>
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MacLennan, A. J., Browe, C. S., Gaskin, A. A., Lado, D. C., Shaw, G.
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<strong>Cloning and characterization of a putative G-protein coupled receptor potentially involved in development.</strong>
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Molec. Cell. Neurosci. 5: 201-209, 1994.
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[PubMed: 8087418]
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[Full Text: https://doi.org/10.1006/mcne.1994.1024]
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<p class="mim-text-font">
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Oskeritzian, C. A., Price, M. M., Hait, N. C., Kapitonov, D., Falanga, Y. T., Morales, J. K., Ryan, J. J., Milstien, S., Spiegel, S.
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<strong>Essential roles of sphingosine-1-phosphate receptor 2 in human mast cell activation, anaphylaxis, and pulmonary edema.</strong>
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<p class="mim-text-font">
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Sanchez, T., Thangada, S., Wu, M.-T., Kontos, C. D., Wu, D., Wu, H., Hla, T.
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<strong>PTEN as an effector in the signaling of antimigratory G protein-coupled receptor.</strong>
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Proc. Nat. Acad. Sci. 102: 4312-4317, 2005.
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<li>
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<p class="mim-text-font">
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Santos, R. L. P., Hassan, M. J., Sikandar, S., Lee, K., Ali, G., Martin, P. E., Jr., Wambangco, M. A. L., Ahmad, W., Leal, S. M.
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<strong>DFNB68, a novel autosomal recessive non-syndromic hearing impairment locus at chromosomal region 19p13.2.</strong>
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Hum. Genet. 120: 85-92, 2006.
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<li>
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<p class="mim-text-font">
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Santos-Cortez, R. L. P., Faridi, R., Rehman, A. U., Lee, K., Ansar, M., Wang, X., Morell, R. J., Isaacson, R., Belyantseva, I. A., Dai, H., Acharya, A., Qaiser, T. A., and 15 others.
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<strong>Autosomal-recessive hearing impairment due to rare missense variants within S1PR2.</strong>
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Am. J. Hum. Genet. 98: 331-338, 2016.
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[PubMed: 26805784]
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[Full Text: https://doi.org/10.1016/j.ajhg.2015.12.004]
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Shimizu, T., Nakazawa, T., Cho, A., Dastvan, F., Shilling, D., Daum, G., Reidy, M. A.
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<strong>Sphingosine 1-phosphate receptor 2 negatively regulates neointimal formation in mouse arteries.</strong>
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Circ. Res. 101: 995-1000, 2007.
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[PubMed: 17872461]
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[Full Text: https://doi.org/10.1161/CIRCRESAHA.107.159228]
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Skoura, A., Sanchez, T., Claffey, K., Mandala, S. M., Proia, R. L., Hla, T.
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<strong>Essential role of sphingosine 1-phosphate receptor 2 in pathological angiogenesis of the mouse retina.</strong>
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J. Clin. Invest. 117: 2506-2516, 2007.
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[PubMed: 17710232]
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[Full Text: https://doi.org/10.1172/JCI31123]
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Marla J. F. O'Neill - updated : 03/15/2016<br>Paul J. Converse - updated : 11/3/2010<br>Patricia A. Hartz - updated : 11/6/2007<br>Patricia A. Hartz - updated : 5/9/2005<br>Patricia A. Hartz - updated : 8/19/2002<br>Ada Hamosh - updated : 7/13/2000<br>Paul J. Converse - updated : 7/10/2000
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Paul J. Converse : 7/6/2000
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carol : 10/19/2017<br>carol : 03/15/2016<br>alopez : 11/30/2015<br>carol : 5/7/2014<br>mgross : 11/4/2010<br>terry : 11/3/2010<br>alopez : 5/5/2009<br>alopez : 5/4/2009<br>terry : 4/28/2009<br>wwang : 9/25/2008<br>carol : 2/29/2008<br>carol : 2/29/2008<br>mgross : 11/6/2007<br>terry : 11/6/2007<br>mgross : 5/10/2005<br>terry : 5/9/2005<br>tkritzer : 3/5/2004<br>alopez : 1/21/2004<br>mgross : 8/19/2002<br>alopez : 7/13/2000<br>alopez : 7/13/2000<br>psherman : 7/11/2000<br>mgross : 7/10/2000<br>mgross : 7/10/2000<br>mgross : 7/6/2000
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